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Plozasiran (ARO-APOC3)

Plozasiran

Severe Hypertriglyceridemialiverphase 3

Plozasiran (formerly ARO-APOC3) is designed to reduce the production of the protein Apolipoprotein-CIII (ApoC3) through the natural RNA interference (RNAi) mechanism.  ApoC3 is a protein that is produced in liver cells and inhibits the formation and clearance of various lipids and lipoproteins, including triglycerides.

The goal of treatment with plozasiran is to reduce the level of ApoC3 thereby reducing triglycerides and restoring lipids to more normal levels.

Clinical Trials

recruitingID: NCT06347003

This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.

recruitingID: NCT06347016

This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After Month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.

completeID: NCT04720534

The purpose of AROAPOC3-2001 is to evaluate the efficacy and safety of ARO-APOC3 in participants with severe hypertriglyceridemia. Participants will receive 2 subcutaneous injections of ARO-APOC3.

completeID: NCT03783377

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).

Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults with Severe Hypertriglyceridemia (SHASTA-3)

Severe HypertriglyceridemiarecruitingID: NCT06347003

This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.

View on ClinicalTrials.gov

Inclusion Criteria

  • Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥ 500 mg/dL (≥5.65mmol/L)
  • Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
  • Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
  • Screening HbA1C ≤8.5%
  • Willing to follow diet counseling and maintain a stable low-fat diet
  • Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Timeline

  • April 4, 2024

    Study First Posted

  • May 2024

    Study Start Date

  • October 2026

    Estimated Completion Date

Trial Details

Start Date:

May 2024

End Date:

October 2026

Participants:

405

Eligibility criteria:

18 Years or Older, All Sexes, No Healthy Volunteers

Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults with Severe Hypertriglyceridemia (SHASTA-4)

Severe HypertriglyceridemiarecruitingID: NCT06347016

This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After Month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.

View on ClinicalTrials.gov

Inclusion Criteria

  • Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of ≥500 mg/dL (≥5.65 mmol/L)
  • Mean fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
  • Fasting low density lipoprotein-cholesterol (LDL-C) ≤130 mg/dL (≤3.37 mmol/L) at screening
  • Screening HbA1C ≤8.5%
  • Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Timeline

  • April 4, 2024

    Study First Posted

  • May 2024

    Study Start Date

  • October 2026

    Estimated Completion Date

Trial Details

Start Date:

May 2024

End Date:

October 2026

Participants:

300

Eligibility criteria:

18 Years or Older, All Sexes, No Healthy Volunteers

A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Severe Hypertriglyceridemia (SHASTA-2)

Severe HypertriglyceridemiacompleteID: NCT04720534

The purpose of AROAPOC3-2001 is to evaluate the efficacy and safety of ARO-APOC3 in participants with severe hypertriglyceridemia. Participants will receive 2 subcutaneous injections of ARO-APOC3.

View on ClinicalTrials.gov

Inclusion Criteria

  • Based on medical history, evidence of TG ≥ 500 mg/dL and ≤ 4000 mg/dL at Screening
  • Fasting TG ≥ 500 mg/dL at Screening
  • Willing to follow diet counseling per Investigator judgment based on local standard of care
  • Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements

Timeline

  • January 2021

    Study First Posted

  • May 2021

    Study Start Date

  • March 2023

    Actual study completion date

Trial Details

Start Date:

May 2021

End Date:

March 2023

Locations:

Australia, Canada, Germany, Hungary, Netherlands, New Zealand, Poland, United States

Participants:

229

Eligibility criteria:

18 Years and older (Adult, Older Adult), All Sexes, No Healthy Volunteers

A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome

Familial Chylomicronemia SyndromecompleteID: NCT03783377

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).

View on ClinicalTrials.gov

Inclusion Criteria

  • Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • Normal electrocardiogram (ECG) at screening
  • Hypertriglyceridemic patients must have a history of fasting serum triglycerides of at least 300 mg/dL (3.38 mmol/L) at screening or verifiable diagnosis of FCS

Timeline

  • December 2018

    Study First Posted

  • March 2019

    Study Start Date

  • February 2021

    Actual study completion date

Trial Details

Start Date:

March 2019

End Date:

February 2021

Locations:

Australia, Canada, New Zealand

Participants:

112

Eligibility criteria:

18 Years to 70 Years (Adult, Older Adult), All Sexes, Accepts Healthy Volunteers

Plozasiran

Familial Chylomicronemia Syndromeliverphase 3

Plozasiran (formerly ARO-APOC3) is designed to reduce the production of the protein Apolipoprotein-CIII (ApoC3) through the natural RNA interference (RNAi) mechanism.  ApoC3 is a protein that is produced in liver cells and inhibits the formation and clearance of various lipids and lipoproteins, including triglycerides.

The goal of treatment with plozasiran is to reduce the level of ApoC3 thereby reducing triglycerides and restoring lipids to more normal levels.

Clinical Trials

activeID: NCT05089084

The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 in adult participants with familial chylomicronemia syndrome (FCS). Participants who have met all eligibility criteria will be randomized to receive 4 doses of ARO-APOC3 or matching placebo administered subcutaneously. Participants who complete the randomized period will continue in a 2-year open-label extension period where all participants will receive ARO-APOC3.

completeID: NCT03783377

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).

A Phase 3 Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Familial Chylomicronemia Syndrome (PALISADE)

Familial Chylomicronemia SyndromeactiveID: NCT05089084

The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 in adult participants with familial chylomicronemia syndrome (FCS). Participants who have met all eligibility criteria will be randomized to receive 4 doses of ARO-APOC3 or matching placebo administered subcutaneously. Participants who complete the randomized period will continue in a 2-year open-label extension period where all participants will receive ARO-APOC3.

View on ClinicalTrials.gov

Inclusion Criteria

  • Fasting TG ≥ 10 mmol/L (≥ 880 mg/dL) at screening refractory to standard lipid lowering therapy
  • Diagnosis of FCS
  • Willing to follow dietary counseling as per investigator judgement based on local standard of care
  • Participants of childbearing potential (males & females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
  • Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding
  • Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1

Timeline

  • October 2021

    Study First Posted

  • January 2022

    Study Start Date

  • April 2024

    Estimated study completion date

Trial Details

Start Date:

January 2022

End Date:

April 2024

Locations:

Argentina, Australia, Austria, Belgium, Canada, Croatia, France, Germany, Ireland, Israel, Japan, Korea, Republic of, Mexico, New Zealand, Oman, Poland, Serbia, Singapore, Spain, Turkey, United States

Participants:

72

Eligibility criteria:

18 Years and older, All Sexes, No Healthy Volunteers

A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome

Familial Chylomicronemia SyndromecompleteID: NCT03783377

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).

View on ClinicalTrials.gov

Inclusion Criteria

  • Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • Normal electrocardiogram (ECG) at screening
  • Hypertriglyceridemic patients must have a history of fasting serum triglycerides of at least 300 mg/dL (3.38 mmol/L) at screening or verifiable diagnosis of FCS

Timeline

  • December 2018

    Study First Posted

  • March 2019

    Study Start Date

  • February 2021

    Actual study completion date

Trial Details

Start Date:

March 2019

End Date:

February 2021

Locations:

Australia, Canada, New Zealand

Participants:

112

Eligibility criteria:

18 Years to 70 Years (Adult, Older Adult), All Sexes, Accepts Healthy Volunteers

Plozasiran

Dyslipidemialiverphase 2

Plozasiran (formerly ARO-APOC3) is designed to reduce the production of the protein Apolipoprotein-CIII (ApoC3) through the natural RNA interference (RNAi) mechanism.  ApoC3 is a protein that is produced in liver cells and inhibits the formation and clearance of various lipids and lipoproteins, including triglycerides.

The goal of treatment with plozasiran is to reduce the level of ApoC3 thereby reducing triglycerides and restoring lipids to more normal levels.

Clinical Trials

completeID: NCT04998201

Participants who have met all protocol eligibility criteria will be randomly assigned to treatment (ARO-APOC3 or placebo) in a double-blind fashion and will be evaluted for safety and efficacy over 48 weeks. Participants will be counseled to remain on a specified diet throughout the study, as recommended by the Investigator in accordance with local standard of care. After week 48, participants will be eligible and invited to consent and continue in an open-label extension study. All placebo participants who opt to continue will switch to active drug (ARO-APOC3) during the extension study.

activeID: NCT05413135

This is an open-label extension of the parent studies AROAPOC3-2001 and AROAPOC3-2002. Adult participants with dyslipidemia who completed the blinded 12-month period from either parent study and continue to meet eligibility criteria have the option to be enrolled into this study. Eligible enrolled participants will initially receive open-label ARO-APOC3 at the assigned dose level until a final dose is selected, at which point all participants will be transitioned to the selected dosing regimen.

A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Mixed Dyslipidemia (MUIR)

DyslipidemiacompleteID: NCT04998201

Participants who have met all protocol eligibility criteria will be randomly assigned to treatment (ARO-APOC3 or placebo) in a double-blind fashion and will be evaluted for safety and efficacy over 48 weeks. Participants will be counseled to remain on a specified diet throughout the study, as recommended by the Investigator in accordance with local standard of care. After week 48, participants will be eligible and invited to consent and continue in an open-label extension study. All placebo participants who opt to continue will switch to active drug (ARO-APOC3) during the extension study.

View on ClinicalTrials.gov

Inclusion Criteria

  • Based on medical history, evidence of TG ≥ 150 mg/dL but ≤ 499 mg/dL on more than one occasion
  • Fasting levels at Screening of non-HDL-C ≥ 100 mg/dL OR LDL-C ≥ 70 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy
  • Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 14 days apart
  • Willing to follow diet counseling as per Investigator judgment based on local standard of care
  • Participants of childbearing potential (males & females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm and females must ot donate eggs during the study and for at least 24 weeks following the last dose of study medication.
  • Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding
  • Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
  • Willing to provide written informed consent and to comply with study requirements

Timeline

  • August 10, 2021

    Study First Posted

  • September 28, 2021

    Study Start Date

  • August 14, 2023

    Study Completion Date

Trial Details

Start Date:

September 2021

End Date:

August 14, 2023

Locations:

Australia, Canada, Hungary, New Zealand, Poland, United States

Participants:

353

Eligibility criteria:

18 Years to 65 Years, All Sexes, No Healthy Volunteers

A Phase 2 Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of ARO-APOC3 in Adults With Dyslipidemia

DyslipidemiaactiveID: NCT05413135

This is an open-label extension of the parent studies AROAPOC3-2001 and AROAPOC3-2002. Adult participants with dyslipidemia who completed the blinded 12-month period from either parent study and continue to meet eligibility criteria have the option to be enrolled into this study. Eligible enrolled participants will initially receive open-label ARO-APOC3 at the assigned dose level until a final dose is selected, at which point all participants will be transitioned to the selected dosing regimen.

View on ClinicalTrials.gov

Inclusion Criteria

  • Adults who are nonpregnant, nonlactating and do not plan to become pregnant during the study
  • Able and willing to provide written informed consent
  • Completed the 48-week study treatment period in the parent study

Timeline

  • June 2022

    Study First Posted

  • July 2022

    Study Start Date

  • October 2025

    Estimated study completion date

Trial Details

Start Date:

July 2022

End Date:

October 2025

Locations:

Australia, Canada, Hungary, Netherlands, New Zealand, Poland, United States

Participants:

536

Eligibility criteria:

18 Years and older (Adult, Older Adult), All sexes, No healthy volunteers

Zodasiran (ARO-ANG3)

Zodasiran

Dyslipidemialiverphase 2

Zodasiran, formally ARO-ANG3, is designed to reduce production of angiopoietin-like protein 3 (ANGPTL3), a liver synthesized inhibitor of lipoprotein lipase and endothelial lipase.

ANGPTL3 inhibition has been shown to lower serum LDL, serum and liver triglyceride and has genetic validation as a novel target for cardiovascular disease.

Clinical Trials

activeID: NCT04832971

The purpose of AROANG3-2001 is to evaluate the efficacy and safety of ARO-ANG3 in participants with mixed dyslipidemia. Participants will initially receive 2 subcutaneous injections of ARO-ANG3 or placebo. Participants who complete the double-blind treatment period may opt to continue in an open-label extension during which they will receive up to 8 doses of ARO-ANG3.

completeID: NCT03747224

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-ANG3 in healthy adult volunteers and in dyslipidemic patients including familial hypercholesterolemia and severe hypertriglyceridemia.

A Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-ANG3 in Adults With Mixed Dyslipidemia (ARCHES-2)

DyslipidemiaactiveID: NCT04832971

The purpose of AROANG3-2001 is to evaluate the efficacy and safety of ARO-ANG3 in participants with mixed dyslipidemia. Participants will initially receive 2 subcutaneous injections of ARO-ANG3 or placebo. Participants who complete the double-blind treatment period may opt to continue in an open-label extension during which they will receive up to 8 doses of ARO-ANG3.

View on ClinicalTrials.gov

Inclusion Criteria

  • Based on medical history, evidence of TG ≥ 150 mg/dL but ≤ 499 mg/dL
  • Fasting levels at Screening of LDL-C ≥ 70 mg/dL OR non-HDL-C ≥ 100 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy
  • Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart
  • Willing to follow diet counseling and maintain a stable diet per Investigator judgment based on local standard of care
  • Participants of childbearing potential must agree to use highly-effective contraception during the study and for at least 24 weeks from last dose of study medication
  • Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
  • Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1
  • Men must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
  • Able and willing to provide written informed consent and to comply with study requirements

Timeline

  • April 2021

    Study First Posted

  • June 2021

    Study Start Date

  • August 2022

    Estimated study completion date

Trial Details

Start Date:

June 2021

End Date:

August 2022

Locations:

Australia, Canada, New Zealand, United States

Participants:

204

Eligibility criteria:

18 Years and older (Adult, Older Adult), All Sexes, No Healthy Volunteers

A Phase 1 Single and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-ANG3 in Adult Healthy Volunteers and in Dyslipidemic Patients

DyslipidemiacompleteID: NCT03747224

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-ANG3 in healthy adult volunteers and in dyslipidemic patients including familial hypercholesterolemia and severe hypertriglyceridemia.

View on ClinicalTrials.gov

Inclusion Criteria

  • Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study
  • Normal electrocardiogram (ECG) at Screening

Timeline

  • November 2018

    Study First Posted

  • January 2019

    Study Start Date

  • May 2021

    Acrtual study completion date

Trial Details

Start Date:

January 2019

End Date:

May 2021

Locations:

Australia, New Zealand

Participants:

93

Eligibility criteria:

18 Years to 70 Years (Adult, Older Adult), All Sexes, Accepts Healthy Volunteers

Zodasiran

Homozygous Familial Hypercholesterolemialiverphase 2

Zodasiran, formally ARO-ANG3, is designed to reduce production of angiopoietin-like protein 3 (ANGPTL3), a liver synthesized inhibitor of lipoprotein lipase and endothelial lipase.

ANGPTL3 inhibition has been shown to lower serum LDL, serum and liver triglyceride and has genetic validation as a novel target for cardiovascular disease.

Clinical Trials

activeID: NCT05217667

Participants with documented homozygous familial hypercholesterolemia (HoFH) who have provided informed consent will receive 2 open-label doses of ARO-ANG3 and be evaluated for safety and efficacy parameters through 36 weeks. Participants who complete the first 36 week treatment period may opt to continue in an additional 24-month extension period during which they will receive up to 8 doses open-label doses of ARO-ANG3.

Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH)(Gateway)

Homozygous Familial HypercholesterolemiaactiveID: NCT05217667

Participants with documented homozygous familial hypercholesterolemia (HoFH) who have provided informed consent will receive 2 open-label doses of ARO-ANG3 and be evaluated for safety and efficacy parameters through 36 weeks. Participants who complete the first 36 week treatment period may opt to continue in an additional 24-month extension period during which they will receive up to 8 doses open-label doses of ARO-ANG3.

View on ClinicalTrials.gov

Inclusion Criteria

  • Fasting LDL-C >100 mg/dL at Screening
  • Weight of ≥ 40 kg and body mass index ≥ 18.5 and ≤ 40 kg/m2
  • Diagnosis of HoFH based on a supportive genetic test or clinical diagnosis
  • On stable maximally tolerated lipid lowering therapy
  • Willing to abide by stable low-fat, low-cholesterol, heart-healthy diet for at least 4 weeks prior to Day 1
  • Participants of childbearing potential (males & females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the last dose of study medication.
  • Women of childbearing potential must have a negative pregnancy test and cannot be breastfeeding
  • Women of childbearing potential on hormonal contraceptives must be stable on the medications for > 2 menstrual cycles prior to Day 1
  • Willing to provide written informed consent and to comply with study requirements

Timeline

  • February 2022

    Study First Posted

  • April 2022

    Study Start Date

  • July 2023

    Estimated study completion date

Trial Details

Start Date:

April 2022

End Date:

July 2023

Locations:

Australia, Canada, South Africa, United States

Participants:

18

Eligibility criteria:

16 Years and older (Child, Adult, Older Adult), All Sexes, No Healthy Volunteers

Olpasiran

Cardiovascular Diseaseliverphase 3

Olpasiran, formerly AMG 890 and ARO-LPA, is designed to reduce production of apolipoprotein A, a key component of lipoprotein(a), which has been genetically linked with increased risk of cardiovascular diseases, independent of cholesterol and LDL levels.

Amgen acquired a worldwide, exclusive license in September 2016, to develop and commercialize olpasiran.

Clinical Trials

activeID: NCT05581303

The primary objective of this study is to compare the effect of treatment with olpasiran, to placebo, on the risk for coronary heart disease death (CHD death), myocardial infarction, or urgent coronary revascularization in participants with atherosclerotic cardiovascular disease (ASCVD) and elevated Lipoprotein(a).

completeID: NCT04270760

Evaluate the effect of olpasiran administered subcutaneously (SC) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp[a]).

A Double-blind, Randomized, Placebo-controlled, Multicenter Study Assessing the Impact of Olpasiran on Major Cardiovascular Events in Participants With Atherosclerotic Cardiovascular Disease and Elevated Lipoprotein(a) (OCEAN(a))

Cardiovascular DiseaseactiveID: NCT05581303

The primary objective of this study is to compare the effect of treatment with olpasiran, to placebo, on the risk for coronary heart disease death (CHD death), myocardial infarction, or urgent coronary revascularization in participants with atherosclerotic cardiovascular disease (ASCVD) and elevated Lipoprotein(a).

View on ClinicalTrials.gov

Inclusion Criteria

  • Age 18 to ≤ 85 years
  • Lp(a)≥ 200 nmol/L during screening
  • History of ASCVD as evidenced by history of either: Myocardial infarction (presumed type 1 event due to plaque rupture/erosion) and/or Coronary revascularization with percutaneous coronary intervention AND at least 1 additional risk factor

Timeline

  • October 14, 2022

    Study First Posted

  • December 14, 2022

    Start Date

  • December 16, 2026

    End Date

Trial Details

Start Date:

December 14, 2022

End Date:

December 16, 2026

Locations:

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, Iceland, Italy, Japan, Korea, Lithuania, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden, Taiwan, United Kingdom, United States

Participants:

6000

Eligibility criteria:

18 Years to 85 Years, All Sexes, No Healthy Volunteers

A Double-blind, Randomized, Placebo-controlled Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Olpasiran (AMG 890) in Subjects With Elevated Lipoprotein(a)

Cardiovascular DiseasecompleteID: NCT04270760

Evaluate the effect of olpasiran administered subcutaneously (SC) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp[a]).

View on ClinicalTrials.gov

Inclusion Criteria

  • Age 18 to 80 years
  • Lipoprotein (a) > 150 nmol/L
  • Evidence of atherosclerotic cardiovascular disease

Timeline

  • February 17, 2022

    Study First Posted

  • July 28, 2022

    Start Date

  • December 27, 2021

    Primary Completion

  • November 8, 2022

    End Date

Trial Details

Start Date:

July 28, 2022

End Date:

November 8, 2022

Locations:

Australia, Canada, Denmark, Iceland, Japan, Netherlands, United States

Participants:

281

Eligibility criteria:

18 Years to 80 Years, All Sexes, No Healthy Volunteers

GSK4532990

NASHliverphase 2

GSK4532990, formerly ARO-HSD, targets HSD17B13, a member of the hydroxysteroid dehydrogenase family involved in the metabolism of hormones, fatty acids, and bile acids. Published human genetic data indicate that a loss of function mutation in HSD17B13 provides strong protection against alcoholic hepatitis, cirrhosis, and NASH, with approximately 30-50% risk reduction compared to non-carriers. GSK4532990 is being developed under the November 2021 exclusive license agreement between Arrowhead and GSK.

Clinical Trials

recruitingID: NCT06104319

The purpose of this study is to understand how the drug GSK4532990 is processed in the body (pharmacokinetics) and how it works in the liver (pharmacodynamics) as well as to ensure it is safe and well-tolerated. The total study duration for each participant will be approximately 24 weeks.

recruitingID: NCT05583344

The purpose of this study is to measure improvements in liver fibrosis and inflammation with GSK4532990 compared with placebo in participants with NASH and advanced (F3) fibrosis. The study duration will be up to 76 weeks including the screening period. The treatment duration will be up to 52 weeks.

completeID: NCT04202354

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple doses of ARO-HSD in healthy adult volunteers and in patients with NASH or suspected NASH.

A Phase 2a, Single Dose, Open-label, Dose Exploration Study to Assess the PK-PD Activity, Safety, and Tolerability of GSK4532990 in Adult. Participants With NASH and Suspected NASH (SKYLINE)

NASHrecruitingID: NCT06104319

The purpose of this study is to understand how the drug GSK4532990 is processed in the body (pharmacokinetics) and how it works in the liver (pharmacodynamics) as well as to ensure it is safe and well-tolerated. The total study duration for each participant will be approximately 24 weeks.

View on ClinicalTrials.gov

Timeline

  • October 27, 2023

    Study First Posted

  • January 1, 2024

    Start Date

  • May 5, 2026

    End Date

Trial Details

Start Date:

January 1, 2024

End Date:

May 5, 2026

Participants:

48

Eligibility criteria:

18 Years to 75 Years, All Sexes, No Healthy Volunteers

A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of GSK4532990 in Adults With Pre-Cirrhotic Nonalcoholic Steatohepatitis (HORIZON)

NASHrecruitingID: NCT05583344

The purpose of this study is to measure improvements in liver fibrosis and inflammation with GSK4532990 compared with placebo in participants with NASH and advanced (F3) fibrosis. The study duration will be up to 76 weeks including the screening period. The treatment duration will be up to 52 weeks.

View on ClinicalTrials.gov

Inclusion Criteria

  • Body Mass Index (BMI) ≥25 kilogram per meter square (kg/m^2) (all ethnic origins) except for Asian participants who qualify for the study with BMI ≥23 kg/m2 at Screening
  • In the opinion of the investigator, there are features of metabolic syndrome and NAFLD is the most likely cause of liver disease. Metabolic syndrome may include type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension
  • A liver biopsy at baseline showing NAFLD Activity Score (NAS) >=4 with at least 1 point each in steatosis, inflammation and ballooning and Fibrosis CRN score of 3
  • Able and willing to comply with all study assessments, including a liver biopsy at Week 52

Timeline

  • October 17, 2022

    Study First Posted

  • January 2, 2023

    Start Date

  • September 8, 2025

    Primary Completion

  • December 15, 2025

    End Date

Trial Details

Start Date:

January 2, 2023

End Date:

December 15, 2025

Locations:

Argentina, Belgium, Canada, France, Greece, India, Italy, Japan, Korea, Mexico, Puerto Rico, Spain, Turkey, United Kingdom, United States

Participants:

246

Eligibility criteria:

18 Years to 75 Years, All Sexes, No Healthy Volunteers

A Phase 1/2a Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-HSD in Normal Healthy Volunteers as Well as in Patients With NASH or Suspected NASH

NASHcompleteID: NCT04202354

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple doses of ARO-HSD in healthy adult volunteers and in patients with NASH or suspected NASH.

View on ClinicalTrials.gov

Inclusion Criteria

  • Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • On a stable diet for at least 4 weeks with no plans to significantly alter diet or weight over course of study
  • Normal electrocardiogram (ECG) at Screening
  • No abnormal finding of clinical relevance (other than NASH, suspected NASH in patients) at Screening that could adversely impact subject safety during the study or adversely impact study results

Timeline

  • December 2019

    Study First Posted

  • March 2020

    Study Start Date

  • September 2021

    Actual study completion date

Trial Details

Start Date:

March 2020

End Date:

September 2021

Locations:

New Zealand

Participants:

50

Eligibility criteria:

19 Years to 65 Years (Adult, Older Adult), All Sexes, Accepts healthy volunteers

ARO-PNPLA3

NASHliverphase 1

ARO-PNPLA3, formerly called JNJ-75220795, is an investigational RNAi therapeutic designed to reduce liver expression of patatin-like phospholipase domain containing 3 (PNPLA3) as a potential treatment for patients with non-alcoholic steatohepatitis (NASH).

PNPLA3 has strong genetic and preclinical validation as a driver of fat accumulation and damage in the livers of patients who carry the common I148M mutation.

Pulmonary

ARO-RAGE

Inflammatory Pulmonary Diseaseslungphase 1

ARO-RAGE is designed to reduce production of the Receptor for Advanced Glycation End products (RAGE) as a potential treatment for various muco-obstructive and inflammatory pulmonary diseases.

Clinical Trials

recruitingID: NCT05276570

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ARO-RAGE in normal healthy volunteers (NHVs) and in participants with inflammatory lung disease. In Part 1 of the study, NHVs will receive a single dose of ARO-RAGE or placebo. In Part 2 of the study, adult participants with inflammatory lung disease will receive 2 doses of ARO-RAGE or placebo. Additional NHVs may be randomized to receive 1 or 2 doses of ARO-RAGE or placebo at Sponsor discretion. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.

completeID: NCT05533294

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-RAGE Injection in normal healthy volunteers.

A Phase 1/2a Study Evaluating the Effects of ARO-RAGE in Healthy Subjects and Patients With Inflammatory Lung Disease

Inflammatory Pulmonary DiseasesrecruitingID: NCT05276570

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ARO-RAGE in normal healthy volunteers (NHVs) and in participants with inflammatory lung disease. In Part 1 of the study, NHVs will receive a single dose of ARO-RAGE or placebo. In Part 2 of the study, adult participants with inflammatory lung disease will receive 2 doses of ARO-RAGE or placebo. Additional NHVs may be randomized to receive 1 or 2 doses of ARO-RAGE or placebo at Sponsor discretion. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.

View on ClinicalTrials.gov

Inclusion Criteria

  • Normal pulmonary function tests at Screening (NHVs only)
  • Confirmed diagnosis of asthma based on source verifiable medical record (asthma patients only)
  • No abnormal finding of clinical relevance at Screening (other than asthma for asthma patients)
  • Stable dose of asthma controller medications for at least 4 weeks prior to Screening (asthma patients only)
  • Non-smoking
  • Able to produce an induced sputum sample at Screening
  • Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception. Males must not donate sperm during the study and for at least 12 weeks following the last dose of study drug
  • Willing to provide written informed consent and to comply with study requirements

Timeline

  • March 2022

    Study First Posted

  • June 2022

    Study Start Date

  • February 2024

    Estimated Study Completion Date

Trial Details

Start Date:

June 2022

End Date:

February 2024

Locations:

Australia, New Zealand

Participants:

121

Eligibility criteria:

18 Years to 65 Years, All Sexes, Accepts Healthy Volunteers

A Phase 1 Study Evaluating the Effects of ARO-RAGE Injection for Subcutaneous Administration in Healthy Subjects

AsthmacompleteID: NCT05533294

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-RAGE Injection in normal healthy volunteers.

View on ClinicalTrials.gov

Inclusion Criteria

  • Normal pulmonary function tests at Screening prior to sputum induction
  • Normal 12-lead electrocardiogram (ECG) at Screening
  • Non-smoking
  • Able to produce an induced sputum sample at Screening
  • Participants of child-bearing potential (male and female) must use highly effective contraception and cannot donate sperm or eggs during the study or for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Women must have a negative pregnancy test and cannot be breastfeeding
  • Willing to provide written informed consent and to comply with study requirements

Timeline

  • September 2022

    Study First Posted

  • November 2022

    Study Start Date

  • February 8, 2024

    Estimated study completion date

Trial Details

Start Date:

November 2022

End Date:

February 8, 2024

Locations:

New Zealand

Participants:

50

Eligibility criteria:

18 Years to 55 Years (Adult), All Sexes, Accepts Healthy Volunteers

ARO-MMP7

Idiopathic Pulmonary Fibrosislungphase 1

ARO-MMP7 is designed to the reduce expression of matrix metalloproteinase 7 (MMP7) as a potential treatment for idiopathic pulmonary fibrosis (IPF).

Clinical Trials

recruitingID: NCT05537025

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-MMP7 in normal healthy volunteers (NHVs) and in participants with idiopathic pulmonary fibrosis (IPF). The study will initiate with NHVs receiving single ascending doses of ARO-MMP7. Following evaluation of safety and pharmacodynamic (PD) data, participants will receive multiple doses of ARO-MMP7.

A Phase 1/2a Study Evaluating the Effects of ARO-MMP7 Inhalation Solution in Healthy Subjects and Patients With Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary FibrosisrecruitingID: NCT05537025

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-MMP7 in normal healthy volunteers (NHVs) and in participants with idiopathic pulmonary fibrosis (IPF). The study will initiate with NHVs receiving single ascending doses of ARO-MMP7. Following evaluation of safety and pharmacodynamic (PD) data, participants will receive multiple doses of ARO-MMP7.

View on ClinicalTrials.gov

Inclusion Criteria (NHVs)

  • Normal pulmonary function tests at Screening
  • Normal electrocardiogram (ECG) at Screening
  • Non-smoking
  • Female participants cannot be pregnant or lactating
  • Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later.

Inclusion Criteria (IPF Participants)

  • Age ≥ 45 years at Screening
  • Clinical diagnosis consistent with IPF based upon established criteria confirmed by review of high-resolution computed tomography (HRCT) and surgical lung biopsy findings (if available)
  • Safely able to undergo bronchoscopy
  • Stable IPF disease at Screening with minimum life expectancy of ≥ 12 months from Screening
  • Female participants cannot be pregnant or lactating
  • Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later.

Timeline

  • September 2022

    Study First Posted

  • January 2023

    Study Start Date

  • August 2024

    Estimated study completion date

Trial Details

Start Date:

January 2023

End Date:

August 2024

Locations:

New Zealand

Participants:

77

Eligibility criteria:

18 Years and older (Adult, Older Adult), all sexes, accepts healthy volunteers

Liver

Fazirsiran

Alpha-1 Liver Diseaseliverphase 3

Fazirsiran is being developed to treat the liver disease associated with alpha-1 antitrypsin deficiency (AATD), a rare genetic disorder that severely damages the liver and lungs of affected individuals.

Fazirsiran is designed to knock down the hepatic production of the mutant alpha-1 antitrypsin (Z-AAT) protein, the cause of progressive liver disease in AATD patients. Reducing production of the inflammatory Z-AAT protein is expected to halt the progression of liver disease and potentially allow it to regenerate and repair.

Clinical Trials

recruitingID: NCT05891158

The main aim of this study is to learn how the body processes fazirsiran (pharmacokinetics [PK]) in people with mild, moderate, or severe liver problems, compared to people with normal liver function.

The study will include participants with liver scarring (cirrhosis) and mild, moderate, or severe liver problems, and participants with normal liver function. All participants will be given 1 injection of fazirsiran and will be followed up for 6 months after the fazirsiran injection.

recruitingID: NCT05899673

The main aim of this study is to learn if fazirsiran is safe during long-term use in people with liver disease caused by the abnormal Z-alpha-1 antitrypsin (Z-AAT) protein. People who are currently taking part in or have completed previous fazirsiran studies (AROAAT2001 [NCT03945292] or AROAAT2002 [NCT03946449]) can continue to receive fazirsiran in this study. Participants will receive fazirsiran every 3 months for almost 2 years and will then be followed for an additional 6 months. The study may also provide information on whether fazirsiran has a long-term effect in reducing liver fibrosis or slowing down the progression of liver fibrosis in people with liver disease due to the abnormal Z-AAT protein.

recruitingID: NCT05677971

The main aim of this study is to learn if fazirsiran reduces liver scarring (fibrosis) compared to placebo. Other aims are to learn if fazirsiran slows down the disease worsening in the liver, to get information on how fazirsiran affects the body (called pharmacodynamics), to learn if fazirsiran reduces other liver injury (inflammation) and the abnormal Z-AAT protein in the liver, to get information on how the body processes fazirsiran (called pharmacokinetics), to test how well fazirsiran works compared with a placebo in improving measures of liver scarring including imaging and liver biomarkers (substances in the blood that the body normally makes and help show if liver function is improving, staying the same, or getting worse) as well as to check for side effects in participants treated with fazirsiran compared with those who received placebo.

Participants will either receive fazirsiran or placebo. Liver biopsies, a way of collecting a small tissue sample from the liver, will be taken twice during this study.

recruitingID: NCT06165341

In some people, the liver makes an abnormal version of the alpha-1 antitrypsin (AAT) protein, called Z-AAT. Making an abnormal version of the AAT protein can result in liver disease as Z-AAT builds up in liver cells, which leads to liver problems such as liver scarring (fibrosis), continuing liver damage (cirrhosis), and eventually endstage liver disease. Fazirsiran is a medicine that reduces the creation of the Z-AAT protein and thus the build-up of this abnormal protein in the liver. People with this type of liver disease who already have mild liver scarring will take part in the study. They will be treated with fazirsiran or a placebo for about 2 years. This study will check the long-term safety of fazirsiran and if participants tolerate the treatment. A liver biopsy, a way of collecting a small tissue sample from the liver, will be taken twice during the study.

completeID: NCT03362242

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-AAT in healthy adult volunteers.

activeID: NCT03946449

Participants will be enrolled to receive multiple subcutaneous injections of fazirsiran (TAK-999, ARO-AAT). All eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. All participants will undergo an End of Study (EOS) biopsy. Treated participants will be offered the opportunity to continue treatment in an open label extension during which they will undergo a final biopsy.

completeID: NCT03945292

Participants will be enrolled to receive multiple subcutaneous injections of Fazirsiran Injection (also referred to as TAK-999 Injection or ARO-AAT Injection) or placebo. Eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. However, any participant with a biopsy result within 1 year of screening showing no fibrosis does not require a pre-dose biopsy. Only participants who have liver fibrosis will undergo a post-dose biopsy and may continue treatment in an open-label phase.

An Open-Label, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics in Response to a Single Subcutaneous Dose of Fazirsiran (TAK-999) in Subjects With or Without Hepatic Impairment

Alpha-1 Liver DiseaserecruitingID: NCT05891158

The main aim of this study is to learn how the body processes fazirsiran (pharmacokinetics [PK]) in people with mild, moderate, or severe liver problems, compared to people with normal liver function.

The study will include participants with liver scarring (cirrhosis) and mild, moderate, or severe liver problems, and participants with normal liver function. All participants will be given 1 injection of fazirsiran and will be followed up for 6 months after the fazirsiran injection.

View on ClinicalTrials.gov

Inclusion Criteria

  • Key Inclusion Criteria for Participants with Hepatic Impairment and Participants with Normal Hepatic Function can be found on clincialtrials.gov
  • Key Inclusion Criteria for Participants with Hepatic Impairment can be found on clincialtrials.gov
  • Key Inclusion Criteria for Participants with Normal Hepatic Function can be found on clincialtrials.gov

Timeline

  • June 6, 2023

    Study First Posted

  • October 5, 2023

    Study Start Date

  • April 15, 2025

    Estimated Completion Date

Trial Details

Start Date:

October 5, 2023

End Date:

April 15, 2025

Locations:

Hungary, Slovakia,

Participants:

41

Eligibility criteria:

18 Years to 85 Years, All Sexes, Accepts Healthy Volunteers

A Phase 3, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Fazirsiran in Participants With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease

Alpha-1 Liver DiseaserecruitingID: NCT05899673

The main aim of this study is to learn if fazirsiran is safe during long-term use in people with liver disease caused by the abnormal Z-alpha-1 antitrypsin (Z-AAT) protein. People who are currently taking part in or have completed previous fazirsiran studies (AROAAT2001 [NCT03945292] or AROAAT2002 [NCT03946449]) can continue to receive fazirsiran in this study. Participants will receive fazirsiran every 3 months for almost 2 years and will then be followed for an additional 6 months. The study may also provide information on whether fazirsiran has a long-term effect in reducing liver fibrosis or slowing down the progression of liver fibrosis in people with liver disease due to the abnormal Z-AAT protein.

View on ClinicalTrials.gov

Inclusion Criteria

  • The participant enrolling in this open-label extension (OLE) study will have participated in a previously qualifying study, and will be considered for eligibility based on the study-specific criteria found on clincialtrials.gov

Timeline

  • June 12, 2023

    Study First Posted

  • August 8, 2023

    Study Start Date

  • May 29, 2026

    Estimated Completion Date

Trial Details

Start Date:

August 8, 2023

End Date:

May 29, 2026

Locations:

Germany

Participants:

37

Eligibility criteria:

18 Years or Older, All Sexes, No Healthy Volunteers

A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Fazirsiran in the Treatment of Alpha-1 Antitrypsin Deficiency-Associated Liver Disease With METAVIR Stage F2 to F4 Fibrosis

Alpha-1 Liver DiseaserecruitingID: NCT05677971

The main aim of this study is to learn if fazirsiran reduces liver scarring (fibrosis) compared to placebo. Other aims are to learn if fazirsiran slows down the disease worsening in the liver, to get information on how fazirsiran affects the body (called pharmacodynamics), to learn if fazirsiran reduces other liver injury (inflammation) and the abnormal Z-AAT protein in the liver, to get information on how the body processes fazirsiran (called pharmacokinetics), to test how well fazirsiran works compared with a placebo in improving measures of liver scarring including imaging and liver biomarkers (substances in the blood that the body normally makes and help show if liver function is improving, staying the same, or getting worse) as well as to check for side effects in participants treated with fazirsiran compared with those who received placebo.

Participants will either receive fazirsiran or placebo. Liver biopsies, a way of collecting a small tissue sample from the liver, will be taken twice during this study.

View on ClinicalTrials.gov

Inclusion Criteria

  • The participant must have a diagnosis of the Z allele homozygotes (PiZZ) genotype AATD. PiZZ diagnosis from source verifiable medical records is permitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not permitted
  • The participant's liver biopsy core sample collected should meet the requirements of the protocol
  • The participant has evidence of METAVIR stage F2, F3, or F4 liver fibrosis, evaluated by a centrally read baseline liver biopsy during the screening period; or confirmed as meeting all the entry criteria by central reading of a previous biopsy conducted within 6 months before the estimated enrollment date using an adequate liver biopsy and slides as defined in the study laboratory manual
  • It must be confirmed that the participant does not have HCC. Participants will be screened for HCC with alpha-fetoprotein (AFP) and abdominal ultrasound. If the participant has any of the following, they will be required to have contrast-enhanced CT or MRI imaging to exclude HCC before randomization
  • n adult participant must have a body mass index (BMI) between 18.0 and 39.0 kilograms per meter square (kg^m2), inclusive
  • The participant is a nonsmoker for at least 12 months before screening

Timeline

  • January 10, 2023

    Study First Posted

  • March 6, 2023

    Study Start Date

  • March 31, 2027

    Primary Completion Date

  • March 31, 2029

    Estimated Completion Date

Trial Details

Start Date:

March 6, 2023

End Date:

March 31, 2029

Locations:

Australia, Austria, Belgium, Canada, France, Germany, Italy, Poland, Portugal, Spain, Switzerland, United States

Participants:

160

Eligibility criteria:

18 Years to 75 Years, All Sexes, No Healthy Volunteers

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Fazirsiran in the Treatment of Alpha-1 Antitrypsin Deficiency-Associated Liver Disease With METAVIR Stage F1 Fibrosis (Fribrosis)

Alpha-1 Liver DiseaserecruitingID: NCT06165341

In some people, the liver makes an abnormal version of the alpha-1 antitrypsin (AAT) protein, called Z-AAT. Making an abnormal version of the AAT protein can result in liver disease as Z-AAT builds up in liver cells, which leads to liver problems such as liver scarring (fibrosis), continuing liver damage (cirrhosis), and eventually endstage liver disease. Fazirsiran is a medicine that reduces the creation of the Z-AAT protein and thus the build-up of this abnormal protein in the liver. People with this type of liver disease who already have mild liver scarring will take part in the study. They will be treated with fazirsiran or a placebo for about 2 years. This study will check the long-term safety of fazirsiran and if participants tolerate the treatment. A liver biopsy, a way of collecting a small tissue sample from the liver, will be taken twice during the study.

View on ClinicalTrials.gov

Timeline

  • December 11, 2023

    Study First Posted

  • January 18, 2024

    Study Start Date

  • August 26, 2028

    Estimated Completion Date

Trial Details

Start Date:

January 18, 2024

End Date:

August 26, 2028

Participants:

50

Eligibility criteria:

18 Years to 75 Years, All Sexes, No Healthy Volunteers

A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Effect of ARO-AAT on Serum Alpha-1 Antitrypsin Levels in Normal Adult Volunteers

Alpha 1-Antitrypsin DeficiencycompleteID: NCT03362242

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-AAT in healthy adult volunteers.

View on ClinicalTrials.gov

Inclusion Criteria

  • Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • Non-smoker for at least one year
  • Normal lung function
  • No abnormal finding of clinical relevance at Screening
  • Normal AAT level at Screening visit

Timeline

  • December 2017

    Study First Posted

  • March 2018

    Study Start Date

  • October 2018

    Actual study completion date

Trial Details

Start Date:

March 2018

End Date:

October 2018

Locations:

New Zealand

Participants:

45

Eligibility criteria:

18 Years to 55 Years (Adult), All Sexes, Accepts Healthy Volunteers

A Pilot Open Label, Multi-dose, Phase 2 Study to Assess the Safety and Efficacy of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)

Alpha-1 Liver DiseaseactiveID: NCT03946449

Participants will be enrolled to receive multiple subcutaneous injections of fazirsiran (TAK-999, ARO-AAT). All eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. All participants will undergo an End of Study (EOS) biopsy. Treated participants will be offered the opportunity to continue treatment in an open label extension during which they will undergo a final biopsy.

View on ClinicalTrials.gov

Inclusion Criteria

  • Diagnosis of AATD
  • Women of childbearing potential must have a negative pregnancy gest, cannot be breast feeding, and must be willing to use contraception
  • Willing to provide written, informed consent and to comply with study requirements
  • Non-smoker for at least 1 year
  • No abnormal findings of clinical relevance at screening

Timeline

  • May 2019

    Study First Posted

  • December 2019

    Study Start Date

  • August 2024

    Estimated Study Completion Date

Trial Details

Start Date:

December 2019

End Date:

August 2024

Locations:

Austria, Germany, United Kingdom

Participants:

16

Eligibility criteria:

18 Years to 75 Years, All Sexes, No Healthy Volunteers

A Placebo-Controlled, Multi-dose, Phase 2 Study to Determine the Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency (AATD) [SEQUOIA]

Alpha-1 Liver DiseasecompleteID: NCT03945292

Participants will be enrolled to receive multiple subcutaneous injections of Fazirsiran Injection (also referred to as TAK-999 Injection or ARO-AAT Injection) or placebo. Eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. However, any participant with a biopsy result within 1 year of screening showing no fibrosis does not require a pre-dose biopsy. Only participants who have liver fibrosis will undergo a post-dose biopsy and may continue treatment in an open-label phase.

View on ClinicalTrials.gov

Inclusion Criteria

  • Diagnosis of AATD
  • Liver biopsy at Screening indicating liver fibrosis (score less than F4); a patient with no fibrosis may participate based on a previous biopsy conducted within one year
  • Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • Non-smoker for at least 1 year
  • No abnormal finding of clinical relevance at Screening

Timeline

  • May 10, 2019

    Study First Posted

  • August 7, 2019

    Study Start Date

  • September 18, 2023

    Actual study completion date

Trial Details

Start Date:

August 7, 2019

End Date:

September 18, 2023

Locations:

Germany, Italy, Netherlands, Portugal, Spain, United States

Participants:

40

Eligibility criteria:

18 Years to 75 Years (Adult, Older Adult), All Sexes, No Healthy Volunteers

ARO-HBV

Hepatitis Bliverphase 2

ARO-HBV, is being developed in collaboration with GSK to be a potentially curative therapy for patients with chronic hepatitis B infection, when used in combination with other direct antivirals. ARO-HBV is a sub-cutaneous, ribonucleic acid interference (RNAi) therapy candidate which is designed to silence all HBV gene products and intervenes upstream of the reverse transcription process where current standard-of-care nucleotide and nucleoside analogues act. The company believes this may allow the body’s natural immune defenses to clear the virus and potentially lead to a functional cure.

Clinical Trials

activeID: NCT04535544

JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via ribonucleic acid interference mechanism. This phase 2 study is designed to evaluate safety and efficacy of JNJ-73763989 in HBV infected patients who are co-infected with HDV. The study consists of 2 parts: Part 1 will evaluate safety, tolerability and antiviral activity of JNJ-73763989 + NA while Part 2 will evaluate the safety and efficacy of the JNJ-73763989 + NA regimen in the treatment of HBV/HDV co-infection. Each part includes 3 phases: Screening phase (from 4 Week up to maximum of 8 weeks), Intervention phase (144 Week for Arm A and 148 Week for Arm B) and Follow-up phase (48 Week). The duration of individual study participation will be between 196 and 204 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HDV ribonucleic acid [RNA], HBV deoxyribonucleic acid [DNA] and antigens) , and pharmacokinetics will be assessed throughout the study.

completeID: NCT04439539

Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + PegIFN-alpha-2a + NA with or without JNJ-56136379 in participants with hepatitis B e antigen (HBeAg) positive chronic infection. The study will be conducted in 4 phases: a screening phase, an induction phase with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and physical examinations. The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but was discontinued as per amendment 6 of the study.

completeID: NCT04585789

The title of protocol reflects the original study design. The study design section is reflecting that the design as of protocol amendment 5 is non-randomized.

completeID: NCT04002752

The purpose of this study is to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Japanese adult participants following single-dose subcutaneous administration of 3 different doses of JNJ-73763989, Dose Level 1 (Panel A), Dose Level 2 (Panel B) or Dose Level 3 (Panel C).

completeID: NCT04208386

The purpose of the study is to evaluate the single-dose pharmacokinetic (PK) of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in participants with liver cirrhosis and various degrees of impaired hepatic function when compared with healthy participants with normal hepatic function and no liver cirrhosis.

completeID: NCT03365947

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-HBV in healthy adult volunteers and participants with hepatitis B virus (HBV).

completeID: NCT03982186

Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate efficacy as measured by proportion of participants who completed 48-week study intervention and qualified for stopping NA treatment at Week 48. The study includes: Screening phase (4 weeks), Double-blind study intervention phase (from Day 1 up to Week 48), and Follow-up phase (48 weeks after end of investigational intervention with a maximum duration of 96 weeks). The duration of individual study participation will be between 100 and 150 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HBsAg seroclearance), and pharmacokinetics will be assessed throughout the study.

completeID: NCT04129554

Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute or chronic infection. It consists of a so-called nucleocapsid in which viral DNA is packed with hepatitis B core protein (HBc) and membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic HBV infection may lead to serious illnesses like cirrhosis and hepatocellular carcinoma (HCC). Oral treatment with NAs is effective at suppressing viral DNA formation and lowering virus concentration in blood to levels below lower limit of quantification (LLOQ). JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism but rarely lead to functional cure defined as sustained loss of HBs Ag and HBV DNA in serum. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for treatment of chronic HBV infection. The aim of study is to evaluate efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone, assessed by HBsAg seroclearance at Week 72 (i.e., 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment in HBeAg negative virologically suppressed chronic hepatitis B (CHB) infected participants who received NA treatment for at least 2 years prior to screening. The study will be 2.3 years and will be conducted in 3 phases: a screening phase (4 weeks), a study intervention phase (48 weeks), and a follow-up phase (48 weeks). Safety will be evaluated by AEs including AEs of special interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical examinations.

completeID: NCT04963738

The purpose of this study is to evaluate the pharmacokinetics (PK) of a single subcutaneous (SC) dose of JNJ-73763989 in adult participants with renal impairment compared with healthy participants with normal renal function.

completeID: NCT04586439

The purpose of the study is to evaluate the single-dose Pharmacokinetics of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in healthy Chinese adult participants at 2 different doses, Dose 1 (Panel A) or Dose 2 (Panel B).

completeID: NCT04667104

This study is an intervention specific appendix to the Hepatitis B wings platform trial (PLATFORMPAHPB2001). The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but has been removed as part of amendment 3 of the study.

A Study of JNJ-73763989 + Nucleos(t)Ide Analog in Participants Co-Infected With Hepatitis B and Hepatitis D Virus (REEF-D)

Hepatitis BactiveID: NCT04535544

JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection via ribonucleic acid interference mechanism. This phase 2 study is designed to evaluate safety and efficacy of JNJ-73763989 in HBV infected patients who are co-infected with HDV. The study consists of 2 parts: Part 1 will evaluate safety, tolerability and antiviral activity of JNJ-73763989 + NA while Part 2 will evaluate the safety and efficacy of the JNJ-73763989 + NA regimen in the treatment of HBV/HDV co-infection. Each part includes 3 phases: Screening phase (from 4 Week up to maximum of 8 weeks), Intervention phase (144 Week for Arm A and 148 Week for Arm B) and Follow-up phase (48 Week). The duration of individual study participation will be between 196 and 204 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HDV ribonucleic acid [RNA], HBV deoxyribonucleic acid [DNA] and antigens) , and pharmacokinetics will be assessed throughout the study.

View on ClinicalTrials.gov

Inclusion Criteria

  • Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
  • Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) co-infection with documentation at least 6 months prior to screening
  • For Part 1: hepatitis D RNA (HDV RNA) greater than or equal to (>=) 1000 international units per milliliter (IU/mL) at screening. For Part 2: must have HDV RNA values >= 500 IU/mL, and must have hepatitis B surface antigen (HBsAg) values less than or equal to (<=) 10000 IU/mL at screening or HDV RNA values at screening are <= 100000 IU/mL
  • Alanine aminotransferase (ALT) greater than upper limit normal (ULN) but less than 10 times (ULN)
  • Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
  • Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
  • Non-cirrhotic participants and participants with compensated cirrhosis (Child Pugh class A) at screening (Part 1) and participants must have absence of cirrhosis and platelet count of >= 140000 per deciliter (dL) for enrollment into Part-2

Timeline

  • September 17, 2020

    Study start date

  • October 16, 2023

    Study completion date

Trial Details

Start Date:

September 17, 2020

End Date:

October 16, 2023

Locations:

52

Eligibility criteria:

18 Years to 65 Years (Adult, Older Adult)

A Study of JNJ-73763989, Pegylated Interferon Alpha-2a, Nucleos(t)Ide Analog (NA) With or Without JNJ-56136379 in Treatment-naive Participants With Hepatitis B e Antigen (HBeAg) Positive Chronic Hepatitis B Virus (HBV) Infection

Hepatitis BcompleteID: NCT04439539

Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via a ribonucleic acid interference (RNAi) mechanism. JNJ-56136379 is an orally administered capsid assembly modulator (CAM) that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + PegIFN-alpha-2a + NA with or without JNJ-56136379 in participants with hepatitis B e antigen (HBeAg) positive chronic infection. The study will be conducted in 4 phases: a screening phase, an induction phase with flexible duration, a consolidation phase with or without PegIFN-α2a and a follow-up phase. Safety assessments will include Adverse Events (AEs), serious AEs of the study interventions, clinical laboratory tests, Electrocardiograms (ECGs), vital signs, and physical examinations. The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but was discontinued as per amendment 6 of the study.

View on ClinicalTrials.gov

Inclusion Criteria

  • Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
  • Currently not treated chronic hepatitis B virus (HBV) infection with alanine transaminase (ALT) less than (<) 2* upper limit of normal (ULN) at screening and HBV deoxyribonucleic acid (DNA) greater than or equal to (>=) 20,000 international units per milliliter (IU/mL)
  • Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
  • Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than or equal to (<=) 9 Kilopascal (kPa) at screening

Timeline

  • September 14, 2020

    Start Date

  • February 13, 2024

    End Date

Trial Details

Start Date:

September 14, 2020

End Date:

February 23, 2024

Participants:

54

A Study to Assess Intrahepatic and Peripheral Changes of Immunologic and Virologic Markers in Chronic Hepatitis B Virus Infection (INSIGHT)

Hepatitis BcompleteID: NCT04585789

The title of protocol reflects the original study design. The study design section is reflecting that the design as of protocol amendment 5 is non-randomized.

View on ClinicalTrials.gov

Inclusion Criteria

  • Medically stable on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
  • Hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening: participants be either currently not treated with HBeAg positive status or virologically (nucleos[t]ide analog [NA]) suppressed with HBeAg negative status
  • Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
  • Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
  • Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
  • Fibroscan liver stiffness measurement less than and equal to (<=) 9 Kilopascal (kPa) within 6 months prior to screening or at the time of screening

Timeline

  • March 11, 2021

    Start Date

  • January 9, 2024

    End Date

Trial Details

Start Date:

March 11, 2021

End Date:

January 9, 2024

Participants:

24

Eligibility criteria:

18 Years to 65 Years (Adult, Older Adult)

A Double-blind, Placebo-controlled, Randomized, Parallel, Single Dose Study to Investigate Pharmacokinetics, Safety, and Tolerability of JNJ-73763989 in Healthy Japanese Adult Participants

Hepatitis BcompleteID: NCT04002752

The purpose of this study is to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Japanese adult participants following single-dose subcutaneous administration of 3 different doses of JNJ-73763989, Dose Level 1 (Panel A), Dose Level 2 (Panel B) or Dose Level 3 (Panel C).

View on ClinicalTrials.gov

Inclusion Criteria

  • Participant must be a Japanese participant who has resided outside Japan for no more than 10 years and whose parents and grandparents are Japanese, as determined by participant's verbal report
  • Participant must have a body mass index (BMI; weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 30.0 kilogram per square meter (kg/m^2) extremes included, and body weight not less than 45.0 kg
  • Participant must be healthy on the basis of physical examination, clinical laboratory tests, medical history, and vital signs performed at screening. In case of abnormalities (except for those listed in the exclusion criteria) a participant may be included after all if the investigator judges the abnormalities not clinically significant or appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
  • A female participant of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test on Day -1
  • A male participant must agree not to donate sperm after enrollment (Day 1) in the study until at least 90 days after receiving the study drug

Timeline

  • July 4, 2019

    Start Date

  • August 23, 2019

    End Date

Trial Details

Start Date:

July 4, 2019

End Date:

August 23, 2019

Participants:

25

A Phase 1, Single-Dose, Open-Label, Parallel-Group Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of JNJ-73763989

Hepatitis BcompleteID: NCT04208386

The purpose of the study is to evaluate the single-dose pharmacokinetic (PK) of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in participants with liver cirrhosis and various degrees of impaired hepatic function when compared with healthy participants with normal hepatic function and no liver cirrhosis.

View on ClinicalTrials.gov

Inclusion Criteria

  • For all participants: Body mass index (BMI) between 18.0 and 38 kilogram per meter square (kg/m^2), (extremes included), and a body weight not less than 50 kilograms (kg) at screening; Woman of childbearing potential must not be pregnant; Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential; Non-smoker or light smoker as defined per protocol
  • For Healthy Participants with Normal Hepatic Function and No Liver Cirrhosis: Demographically comparable to the study groups with hepatic impairment with respect to sex, age (+/-10 years), and body weight (+/-10 kg); Participants must be in good health clinically and biologically as defined per protocol
  • For Participants with Liver Cirrhosis and Moderate or Mild or Severe Hepatic Impairment: Must have a total Child-Pugh score of 5 or 6, inclusive (mild); or 7 to 9, inclusive (moderate); or 10 to 15, inclusive (severe) as determined by the investigator; Must have liver cirrhosis with fibro scan readout greater than (>) 12.5 Kilopascal (kPa) as cut-off at screening
  • Participants with controlled hypertension, with problems directly associated with the primary diagnosis of hepatic impairment may be included. Participants may have concurrent stable medical conditions and may be included in the study if the investigator and the sponsor consider that the condition(s) will not introduce an additional risk factor and will not interfere with the study objectives and the procedures (that is, participants with mild degenerative joint disease, controlled diabetes, controlled thyroid conditions, other conditions addressed on a case by case basis)
  • Concomitant medications to treat underlying disease states or medical conditions related to hepatic impairment are allowed

Timeline

  • N/A

    Start Date

  • July 20, 2020

    End Date

Trial Details

Start Date:

N/A

End Date:

July 20, 2020

Participants:

16

A Phase 1/2a Single Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-HBV in Normal Adult Volunteers and Multiple Escalating Doses Evaluating Safety, Tolerability and Pharmacodynamic Effects in HBV Patients

Hepatitis BcompleteID: NCT03365947

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-HBV in healthy adult volunteers and participants with hepatitis B virus (HBV).

View on ClinicalTrials.gov

Inclusion Criteria for Parts A & B

  • Women of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use contraception.
  • Willing to provide written informed consent and comply with study requirements

Additional Inclusion Criteria for Part B

  • Diagnosis of chronic HBV infection
  • HbsAg at screening > or = 50 IU/mL
  • Liver Elastography score < or = 10.5

Timeline

  • December 2017

    Study First Posted

  • March 2018

    Study Start Date

  • April 2020

    Actual study completion date

Trial Details

Start Date:

March 2018

End Date:

April 2020

Locations:

Australia, Hong Kong, New Zealand

Participants:

114

Eligibility criteria:

18 Years to 65 Years (Adult, Older Adult), All Sexes, Accepts Healthy Volunteers

A Study of Different Combination Regimens Including JNJ-73763989 and/or JNJ-56136379 for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1)

Hepatitis BcompleteID: NCT03982186

Hepatitis B virus (HBV) is a small deoxyribonucleic acid virus that specifically infects the human liver. The acute phase of infection is either followed by an immune controlled state or progresses to chronic hepatitis B. The worldwide estimated prevalence of chronic HBV infection is about 292 million people affected. Hepatitis B surface antigen (HBsAg) seroclearance is currently considered to be associated with the most thorough suppression of HBV replication (termed functional cure). With current available NA treatment strategies, rate of HBsAg seroclearance remains very low (around 3 percent [%]) even under long-term treatment. Also, with the persistently high global prevalence of HBV-associated mortality, there is a medical need for more effective finite treatment options that lead to sustained HBsAg seroclearance. JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for the treatment of chronic HBV infection. The aim of the study is to evaluate efficacy as measured by proportion of participants who completed 48-week study intervention and qualified for stopping NA treatment at Week 48. The study includes: Screening phase (4 weeks), Double-blind study intervention phase (from Day 1 up to Week 48), and Follow-up phase (48 weeks after end of investigational intervention with a maximum duration of 96 weeks). The duration of individual study participation will be between 100 and 150 weeks. Safety and tolerability (including adverse events [AEs] and Serious AEs, laboratory assessments, electrocardiogram [ECG], vital signs, physical examination), efficacy (including HBsAg seroclearance), and pharmacokinetics will be assessed throughout the study.

View on ClinicalTrials.gov

Inclusion Criteria

  • Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
  • Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
  • Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
  • Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
  • Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
  • Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening

Timeline

  • March 29, 2021

    Study start date

  • April 26, 2022

    Study completion date

Trial Details

Start Date:

March 29, 2021

End Date:

April 26, 2022

Participants:

471

Eligibility criteria:

18 Years to 65 Years (Adult, Older Adult)

A Study of JNJ 73763989+JNJ 56136379+Nucleos(t)Ide Analog (NA) Regimen Compared to NA Alone in e Antigen Negative Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection

Hepatitis BcompleteID: NCT04129554

Hepatitis B virus (HBV) is a small deoxyribonucleic acid (DNA) virus that infects the liver and can cause either acute or chronic infection. It consists of a so-called nucleocapsid in which viral DNA is packed with hepatitis B core protein (HBc) and membranous envelope containing hepatitis B surface antigen (HBsAg). Chronic HBV infection may lead to serious illnesses like cirrhosis and hepatocellular carcinoma (HCC). Oral treatment with NAs is effective at suppressing viral DNA formation and lowering virus concentration in blood to levels below lower limit of quantification (LLOQ). JNJ-73763989 is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic HBV infection via ribonucleic acid interference mechanism but rarely lead to functional cure defined as sustained loss of HBs Ag and HBV DNA in serum. JNJ-56136379 is an orally administered capsid assembly modulator that is being developed for treatment of chronic HBV infection. The aim of study is to evaluate efficacy of 48-week study intervention with JNJ-3989+JNJ-6379+NA regimen compared to NA alone, assessed by HBsAg seroclearance at Week 72 (i.e., 24 weeks after completion of all study interventions at Week 48) without restarting NA treatment in HBeAg negative virologically suppressed chronic hepatitis B (CHB) infected participants who received NA treatment for at least 2 years prior to screening. The study will be 2.3 years and will be conducted in 3 phases: a screening phase (4 weeks), a study intervention phase (48 weeks), and a follow-up phase (48 weeks). Safety will be evaluated by AEs including AEs of special interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical examinations.

View on ClinicalTrials.gov

Inclusion Criteria

  • Medically stable based on physical examination, medical history, vital signs, electrocardiogram (ECG) at screening
  • Chronic hepatitis B virus (HBV) infection with documentation at least 6 months prior to screening
  • Hepatitis B e (antigen) (HBeAg)-negative on stable nucleotide analogue (NA) treatment for at least 24 months prior to screening
  • Hepatitis B surface antigen (HBsAg) greater than (>) 100 International Units per Milliliter (IU/mL) at screening
  • Body mass index (BMI) between 18.0 and 35 kilogram per meter square (kg/m^2), extremes included
  • Highly effective contraceptive measures in place for female participants of childbearing potential or male participants with female partners of childbearing potential
  • Liver fibrosis stage 0-2 (Metavir) or Fibroscan less than (<) 9 Kilopascal (kPa) at screening

Timeline

  • N/A

    Start Date

  • June 9, 2022

    End Date

Trial Details

Start Date:

N/A

End Date:

June 9, 2022

Participants:

130

A Study of JNJ-73763989 in Adult Participants With Renal Impairment

Hepatitis BcompleteID: NCT04963738

The purpose of this study is to evaluate the pharmacokinetics (PK) of a single subcutaneous (SC) dose of JNJ-73763989 in adult participants with renal impairment compared with healthy participants with normal renal function.

View on ClinicalTrials.gov

Inclusion Criteria

  • Must have stable renal function defined as a less than (<) 20 percent (%) change in serum creatinine concentrations between screening and Day -1
  • Concomitant medications should be stable for the previous 1 month and throughout the duration of the study
  • Women, except for postmenopausal women, must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and urine (beta-hCG) pregnancy test on Day -1
  • Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for the study and are willing to participate in the study
  • Participants with kidney disease without dialysis using benzodiazepines, tricyclic antidepressants, and prescription opiates with a positive urine test for drugs prescribed by their physician may be included following prior discussion with the sponsor

Timeline

  • September 22, 2021

    Start Date

  • October 17, 2022

    End Date

Trial Details

Start Date:

September 22, 2021

End Date:

October 17, 2022

Participants:

29

A Study of JNJ-73763989 in Healthy Chinese Adult Participants

Hepatitis BcompleteID: NCT04586439

The purpose of the study is to evaluate the single-dose Pharmacokinetics of JNJ-73763976 and JNJ-73763924 following a subcutaneous (SC) injection of JNJ-73763989 (JNJ-3989) in healthy Chinese adult participants at 2 different doses, Dose 1 (Panel A) or Dose 2 (Panel B).

View on ClinicalTrials.gov

Inclusion Criteria

  • Participant must be healthy based on physical examination, laboratory assessment, vital signs and electrocardiogram (ECG) at screening
  • A female participant of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [hCG]) pregnancy test at screening and a negative urine pregnancy test on Day -1
  • A male participant must agree not to donate sperm after enrollment (Day 1) in the study and a female participant must agree not to donate eggs (ova, oocytes) during the study until at least 90 days after receiving the study drug
  • Participant must not use nicotine-containing substances including tobacco products for at least 3 months prior to screening until completion of the study
  • Participant must have suitable veins for cannulation and/or repeated venipuncture

Timeline

  • N/A

    Study start date

  • February 18, 2021

    Study Completion date

Trial Details

Start Date:

N/A

End Date:

February 18, 2021

Participants:

18

Eligibility criteria:

18 Years to 55 Years (Adult)

A Study of JNJ-73763989, JNJ-56136379, Nucleos(t)Ide Analogs, and Pegylated Interferon Alpha-2a in Virologically Suppressed Participants With Chronic Hepatitis B Virus Infection (PENGUIN)

Hepatitis BcompleteID: NCT04667104

This study is an intervention specific appendix to the Hepatitis B wings platform trial (PLATFORMPAHPB2001). The study title reflects the original study design and JNJ-56136379 (JNJ-6379) was initially part of the study intervention but has been removed as part of amendment 3 of the study.

View on ClinicalTrials.gov

Inclusion Criteria

  • Chronic hepatitis B virus (HBV) infection, hepatitis B e Antigen (HBeAg) positive or negative with suppressed viral replication under nucleos(t)ide analogue treatment for at least 6 months prior to screening
  • Medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
  • Body mass index (BMI) between 18.0 and 35.0 kilogram per meter square (kg/m^2), extremes included
  • Must have serum HBsAg greater than (>) 100 international units per milliliter (IU/mL) at screening, as assessed by quantitative HBsAg assay
  • Must have a fibroscan stiffness measurement less than or equal to (<=) 9.0 Kilopascal (kPa) at screening

Timeline

  • February 1, 2021

    Start Date

  • April 17, 2023

    End Date

Trial Details

Start Date:

February 1, 2021

End Date:

April 17, 2023

Participants:

48

Eligibility criteria:

18 Years and older, All Sexes, No Healthy Volunteers

Muscular

ARO-DUX4

FSHDmusclephase 1

ARO-DUX4 is an RNA interference (RNAi) conjugate designed to specifically target the gene that encodes human double homeobox 4 (DUX4) protein as a potential treatment for patients with facioscapulohumeral muscular dystrophy type 1 (FSHD1). FSHD1 is an autosomal dominant disease associated with the failure to maintain complete epigenetic suppression of DUX4 expression in differentiated skeletal muscle, leading to overexpression of DUX4, which is myotoxic and can lead to muscle degeneration. Published literature suggests that the silencing of aberrantly transcribed DUX4 mRNA using ARO-DUX4 may halt progression of, and possibly reverse, DUX4-induced muscle toxicities in patients with FSHD1, improving muscle strength and function.

Clinical Trials

recruitingID: NCT06131983

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-DUX4 in participants with facioscapulohumeral muscular dystrophy Type 1 (FSHD1). In Part 1 of the study, participants will receive a single dose of ARO-DUX4 or placebo. In Part 2 of the study, participants will receive 2 or 4 doses of ARO-DUX4 or placebo. Participants who complete Part 1 will have the option to re-screen and re-randomize into Part 2. All participants will undergo pre- and post-dose MRI-guided muscle biopsies (a total of 2 biopsies). Participants who complete Part 1 and enroll in Part 2 will be required to undergo an additional screening biopsy. Participants completing Part 1 or Part 2 may have the option to continue to receive drug in an open-label extension study or may be eligible to participate in later-stage clinical studies.

A Phase1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DUX4 in Adult Patients With Facioscapulohumeral Muscular Dystrophy Type 1

FSHDrecruitingID: NCT06131983

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ARO-DUX4 in participants with facioscapulohumeral muscular dystrophy Type 1 (FSHD1). In Part 1 of the study, participants will receive a single dose of ARO-DUX4 or placebo. In Part 2 of the study, participants will receive 2 or 4 doses of ARO-DUX4 or placebo. Participants who complete Part 1 will have the option to re-screen and re-randomize into Part 2. All participants will undergo pre- and post-dose MRI-guided muscle biopsies (a total of 2 biopsies). Participants who complete Part 1 and enroll in Part 2 will be required to undergo an additional screening biopsy. Participants completing Part 1 or Part 2 may have the option to continue to receive drug in an open-label extension study or may be eligible to participate in later-stage clinical studies.

View on ClinicalTrials.gov

Inclusion Criteria

  • Genetically confirmed FSHD1 based on Screening evaluation or source verifiable medical record
  • Clinical severity score between 3 and 8 (scale, 0 to 10)
  • Must have eligible lower extremity muscle for biopsy as determined from MRI by a central reader
  • A 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety in the study
  • Participants of childbearing potential and their partners must use highly effective contraception during the study and for at least 12 weeks following the end of study or last dose of study medication, whichever is later. Males must not donate sperm during the study from Day 1 until at least 12weeks following the end of study or last dose of study medication, whichever is later

Timeline

  • November 15, 2023

    Study First Posted

  • January 2024

    Study Start Date

  • April 2025

    Primary Completion Date

  • June 2025

    Estimated Completion Date

Trial Details

Start Date:

January 2024

End Date:

June 2025

Participants:

52

Eligibility criteria:

18 Years to 70 Years, All Sexes, No Healthy Volunteers

ARO-DM1

Myotonic Dystrophy Type 1musclephase 1

ARO-DM1 for injection is an RNA interference (RNAi) conjugate designed to specifically silence DMPK mRNA in skeletal muscle. Published literature suggests that the silencing of aberrantly transcribed DMPK mRNA using ARO-DM1 may halt CUGexp-related spliceopathies in patients with DM1 leading to improved muscle strength and function. It belongs to a class of medicines called RNA therapeutics.

Clinical Trials

recruitingID: NCT06138743

This is a Phase 1/2a double-blinded, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses of ARO-DM1 compared to placebo in male and female subjects with Type 1 Myotonic Dystrophy (DM1). Participants who have provided written informed consent and met all protocol eligibility requirements will be randomized to receive single (Part 1) or multiple (Part 2) doses of ARO-DM1 or placebo.

A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DM1 in Subjects With Type 1 Myotonic Dystrophy Who Are ≥18 to ≤ 65 Years

Myotonic Dystrophy Type 1recruitingID: NCT06138743

This is a Phase 1/2a double-blinded, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses of ARO-DM1 compared to placebo in male and female subjects with Type 1 Myotonic Dystrophy (DM1). Participants who have provided written informed consent and met all protocol eligibility requirements will be randomized to receive single (Part 1) or multiple (Part 2) doses of ARO-DM1 or placebo.

View on ClinicalTrials.gov

Inclusion Criteria

  • Genetically confirmed diagnosis of DM1
  • Clinician-assessed signed of DM1 including clinically apparent myotonia
  • Onset of DM1 symptoms occurred after the age of 12 years
  • Walk for at least 10 meters independently at Screening
  • Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of study or last dose of study drug whichever is later

Timeline

  • November 18, 2023

    Study First Posted

  • January 2024

    Start Date

  • October 2025

    End Date

Trial Details

Start Date:

January 2024

End Date:

October 2025

Participants:

48

Eligibility criteria:

18 Years to 65 Years, All Sexes, No Healthy Volunteers

Complement Mediated Disease

ARO-C3

Complement Mediated Diseaseliverphase 1

ARO-C3 is designed to reduce production of complement component 3 as a potential treatment for various complement mediated diseases.

Clinical Trials

recruitingID: NCT05083364

The purpose of AROC3-1001 is to evaluate the safety, tolerability, pharmacokinetics and/or pharmacodynamics in adult healthy volunteers (HVs) and in adult patients with complement-mediated renal disease (C3 Glomerulopathy [C3G] and IgA Nephropathy [IgAN]). In Part 1 of the study, HVs will receive either one or two doses of ARO-C3 or placebo. In Part 2 of the study, adult patients with C3G/IgAN will receive 3 open-label doses of ARO-C3. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.

A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and/or Pharmacodynamics of ARO-C3 in Adult Healthy Volunteers and in Adult Patients With Complement-Mediated Renal Disease

C3 GlomerulopathyrecruitingID: NCT05083364

The purpose of AROC3-1001 is to evaluate the safety, tolerability, pharmacokinetics and/or pharmacodynamics in adult healthy volunteers (HVs) and in adult patients with complement-mediated renal disease (C3 Glomerulopathy [C3G] and IgA Nephropathy [IgAN]). In Part 1 of the study, HVs will receive either one or two doses of ARO-C3 or placebo. In Part 2 of the study, adult patients with C3G/IgAN will receive 3 open-label doses of ARO-C3. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.

View on ClinicalTrials.gov

Inclusion Criteria

  • Willing to provide written informed consent and to comply with study requirements
  • Female participants must be non-pregnant/non-lactating
  • Healthy volunteers must be willing to be vaccinated with a meningococcal and pneumococcal vaccine. C3G and IgAN participants must have been vaccinated or willing to undergo vaccination
  • All participants must be willing to be vaccinated or have a history of vaccination for Haemophilus influenzae
  • Body Mass Index (BMI) between 18.0 and 35.0 kg/m2
  • 12-lead electrocardiogram (ECG) at Screening with no abnormalities that may compromise participant's safety at discretion of investigator
  • Participants of childbearing potential must use highly effective contraception during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later. Males must not donate sperm during the study and for at least 12 weeks following the end of the study or last dose of study drug, whichever is later.
  • No abnormal finding of clinical relevance at the Screening evaluation that, in the opinion of the investigator, could adversely impact participant safety or study results

Timeline

  • October 2021

    Study First Posted

  • February 2022

    Study Start Date

  • December 2024

    Estimated Study Completion Date

Trial Details

Start Date:

February 2022

End Date:

December 2024

Locations:

Australia, Georgia, Germany, Korea, New Zealand, Spain, Thailand, United Kingdom,

Participants:

60

Eligibility criteria:

18 Years to 70 Years (Adult, Older Adult), All Sexes, Accepts Healthy Volunteers

ARO-CFB

Complement Mediated Diseaseliverphase 1

ARO-CFB is designed to reduce hepatic expression of complement factor B (CFB), which plays an important regulatory role in amplifying complement alternative pathway activation and has been identified as a promising therapeutic target for renal and non-renal complement diseases involving complement activation.
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