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Severe Hypertriglyceridemia

What is Hypertriglyceridemia?

Hypertriglyceridemia occurs when levels of triglycerides in the blood are elevated beyond normal levels. Triglycerides are a type of fat that provide energy. When the levels of triglycerides get too high, they can cause negative health outcomes. Triglycerides levels over 150 mg/dL are considered elevated and levels over 500 mg/dL are considered severely elevated.

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  • Hypertriglyceridemia can be caused by various underlying medical conditions, such as diabetes, hypothyroidism, and kidney disease. It can also be caused by medications, genetic lipid disorders, and lifestyle factors.
  • Hypertriglyceridemia is diagnosed through a simple blood test. It is important to consider family history, medical history, and medications when trying to identify the cause.
  • Women have additional risk factors for hypertriglyceridemia, which include menopause and pregnancy.

1 in 5

Adults in the U.S. have elevated triglyceride levels.

42%

Of adults over age 60 in the U.S. have hypertriglyceridemia

Our Research

Plozasiran

Severe Hypertriglyceridemia liver phase 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

planned ID: 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.

planned ID: 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.

complete ID: 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.

complete ID: 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 Hypertriglyceridemia planned ID: 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.

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 Hypertriglyceridemia planned ID: 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.

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 Hypertriglyceridemia complete ID: 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.

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

Severe Hypertriglyceridemia complete ID: 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).

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 Syndrome liver phase 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

active ID: 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.

complete ID: 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 Syndrome active ID: 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.

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 Syndrome complete ID: 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).

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

Active Clinical Trials

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

Gout planned ID: 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.

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

planned

Gout ID: 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.

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

Gout planned ID: 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.

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

planned

Gout ID: 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.

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

active ID: 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.

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

active

ID: 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.

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