Pipeline
Familial Chylomicronemia Syndrome
In Market
Severe Hypertriglyceridemia
Phase 3
Hypertriglyceridemia
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 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).
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.
December 2018
Study First Posted
March 2019
Study Start Date
February 2021
Actual Study Completion Date
Start date:
End date:
Locations:
Australia, Canada, New Zealand
Participants:
112
Eligibility criteria:
18 Years to 70 Years (Adult, Older Adult), All Sexes, Accepts Healthy Volunteers
October 2021
January 2022
April 2024
Estimated Study Completion Date
Argentina, Australia, Austria, Belgium, Canada, Croatia, France, Germany, Ireland, Israel, Japan, Korea, Mexico, New Zealand, Oman, Poland, Serbia, Singapore, Spain, Turkey, United States
72
18 Years and older, All Sexes, No Healthy Volunteers
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.
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.
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.
April 4, 2024
May 2024
October 2026
Estimated Completion Date
405
18 Years or Older, All Sexes, No Healthy Volunteers
300
January 2021
May 2021
March 2023
Actual study Completion Date
Australia, Canada, Germany, Hungary, Netherlands, New Zealand, Poland, United States
229
18 Years and older (Adult, Older Adult), All Sexes, No Healthy Volunteers
This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with hypertriglyceridemia (HTG). 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.
1328
Homozygous Familial Hypercholesterolemia
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.
This multicenter, randomized, placebo-controlled study will evaluate the efficacy and safety of zodasiran subcutaneous (SC) injection in subjects 12 years of age and older with genetically or clinically diagnosed Homozygous familial hypercholesterolemia (HoFH). After completion of the double blind (DB) treatment period subjects will be eligible to continue in the optional open-label extension (OLE) period of the study. All placebo subjects who opt to continue will transition to active drug during the OLE Period.
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.
June 25, 2025
June 17, 2025
August 20, 2027
United States
60
12 Years or Older, All Sexes, No Healthy Volunteers
February 2022
April 2022
July 2023
Australia, Canada, South Africa, United States
18
16 Years and older (Child, Adult, Older Adult), All Sexes, No Healthy Volunteers
Cardiovascular Disease
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.
The primary objective is to evaluate the effect of olpasiran, compared to placebo, on the risk for coronary heart disease death (CHD death), myocardial infarction, or urgent coronary revascularization in participants at risk for a first major cardiovascular event with elevated lipoprotein(a) (Lp[a]).
Evaluate the effect of olpasiran administered subcutaneously (SC) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp[a]).
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).
August 22, 2025
October 20, 2031
Australia, Canada, United States
11000
50 Years to 105 Years, All Sexes, No Healthy Volunteers
February 17, 2022
July 28, 2022
Start Date
December 27, 2021
Primary Completion
November 8, 2022
End Date
Australia, Canada, Denmark, Iceland, Japan, Netherlands, United States
281
18 Years to 80 Years, All Sexes, No Healthy Volunteers
October 14, 2022
December 14, 2022
December 16, 2026
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
6000
18 Years to 85 Years, All Sexes, No Healthy Volunteers
MASH
Phase 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.
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.
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.
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.
October 17, 2022
January 2, 2023
September 8, 2025
December 15, 2025
Argentina, Belgium, Canada, France, Greece, India, Italy, Japan, Korea, Mexico, Puerto Rico, Spain, Turkey, United Kingdom, United States
246
18 Years to 75 Years, All Sexes, No Healthy Volunteers
October 27, 2023
January 1, 2024
May 5, 2026
48
December 2019
March 2020
September 2021
New Zealand
50
19 Years to 65 Years (Adult, Older Adult), All Sexes, Accepts healthy volunteers
Mixed Hyperlipidemia
Phase 1
ARO-DIMER-PA is a dual-functional RNAi molecule designed to silence expression of both PCSK9 and APOC3 genes in hepatocytes. Prior clinical experience with other investigational and approved agents suggests that PCSK9 and APOC3 inhibition may lead to robust reductions in LDL-C, TGs, triglyceride rich lipoprotein remnants, and total atherogenic lipoproteins.
ARO-DIMER-PA is the first clinical candidate designed to selectively silence the expression of two genes with a single RNAi molecule.
Study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD), and effects on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) of single-dose ARO-DIMERPA and multiple doses of ARO-DIMERPA in adult participants with mixed hyperlipidemia.
November 03, 2025
December 22, 2025
July 2027
78
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.
Obesity
ARO-INHBE is designed to reduce the hepatic expression of the INHBE gene and its secreted gene product, Activin E. INHBE is a promising genetically validated target in which loss-of-function INHBE variants in humans are associated with lower risk of obesity and metabolic diseases, such as type 2 diabetes. Activin E acts as a ligand in a pathway that regulates energy homeostasis in adipose tissue. Intervening in this pathway with investigational ARO-INHBE treatment has the potential to increase lipolysis, and reduce adipose hypertrophy and dysfunction, visceral adiposity, and insulin resistance.
This is a Phase 1/2a double-blind dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of ARO-INHBE in adult participants with obesity (Part 1), and the safety, tolerability and PD of repeat doses of ARO-INHBE in adult participants with obesity with and without type 2 diabetes mellitus receiving tirzepatide (Part 2). Part 2 will commence after evaluation of safety data from Part 1 multiple-dose cohorts through Day 43. The dose for Part 2 will be based upon evaluation of data from Part 1.
November 22, 2024
December 2024
January 2026
18 to 65 Years Old, All Sexes, No Healthy Volunteers
ARO-ALK7 is designed to silence adipocyte expression of the ACVR1C gene to reduce production of Activin receptor-like kinase 7 (ALK7), which acts as a receptor in a pathway that regulates energy homeostasis in adipose tissue. In large genetic datasets, reduced ACVR1C expression has been associated with healthier adipose distribution and reduced risk of obesity-related metabolic complications. Treatment with investigational ARO-ALK7 has the potential to reduce visceral adiposity and improve lipid and glycemic parameters.
This study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of ARO-ALK7 in adult volunteers with obesity without Type 2 Diabetes Mellitus (T2DM) (Part 1) and the safety, tolerability, and PD of multiple doses of ARO-ALK7 in adult volunteers with obesity with and without (T2DM) receiving tirzepatide (Part 2).
April 22, 2025
May 5, 2025
July 2026
Australia, New Zealand
126
Alzheimer’s Disease
ARO-MAPT is designed to silence CNS expression of the microtubule associated protein tau (MAPT) gene, which encodes the tau protein. Aggregation of the toxic tau protein is believed to be a key driver in multiple tauopathies, including Alzheimer’s disease. By preventing or potentially reversing tau protein accumulation in subjects with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease dementia, ARO-MAPT has potential to prevent or slow disease progression.
Study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ARO-MAPT-SC compared to placebo in adult healthy volunteers and in participants with early Alzheimer's disease (AD), defined as mild cognitive impairment due to AD and mild AD dementia.
October 27, 2025
November 18, 2025
June 2027
18 to 75 Years Old, All Sexes, Accepts Healthy Volunteers
Spinocerebellar Ataxia 2
ARO-ATXN2 is designed to silence expression of the toxic ATXN2 protein in the Central Nervous System as a potential treatment for spinocerebellar ataxia 2 (SCA2).
Adult participants with spinocerebellar ataxia type 2 (SCA2) who carry ≥33 cytosine, adenine, guanine (CAG) repeats in the ATXN2 gene, and who have met all protocol eligibility criteria will be randomized to receive a single dose of ARO-ATXN2 or placebo and be evaluated for safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters.
November 4, 2024
January 2025
September 2026
36
Huntington’s Disease
Sarepta expects to initiate this first-in-human clinical trial of SRP-1005 (formerly ARO-HTT) in the second quarter of 2026. SRP-1005 is an investigational small interfering RNA (siRNA) therapeutic for the treatment of Huntington’s Disease.
Inflammatory Pulmonary Diseases
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.
The purpose of this study is to evaluate the impact of inhaled ARO-RAGE on the late asthmatic response (LAR) following an inhaled allergen challenge in participants with mild atopic asthma.
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.
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.
November 21, 2025
December 2025
April 2028
March 2022
June 2022
February 2024
121
18 Years to 65 Years, All Sexes, Accepts Healthy Volunteers
September 2022
November 2022
February 8, 2024
18 Years to 55 Years (Adult), All Sexes, Accepts Healthy Volunteers
Idiopathic Pulmonary Fibrosis
ARO-MMP7 is designed to the reduce expression of matrix metalloproteinase 7 (MMP7) as a potential treatment for idiopathic pulmonary fibrosis (IPF).
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.
January 2023
August 2024
77
18 Years and older (Adult, Older Adult), all sexes, accepts healthy volunteers
Alpha-1 Liver Disease
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.
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.
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.
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.
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.
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.
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.
The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, efficacy and tolerability of multiple doses of the investigational product, Fazirsiran Injection, administered subcutaneously to participants with alpha-1 antitrypsin deficiency (AATD).
June 6, 2023
October 5, 2023
April 15, 2025
Hungary, Slovakia
41
18 Years to 85 Years, All Sexes, Accepts Healthy Volunteers
June 12, 2023
August 8, 2023
May 29, 2026
Germany
37
January 10, 2023
March 6, 2023
March 31, 2027
Primary Completion Date
March 31, 2029
Australia, Austria, Belgium, Canada, France, Germany, Italy, Poland, Portugal, Spain, Switzerland, United States
160
December 11, 2023
January 18, 2024
August 26, 2028
May 2019
Austria, Germany, United Kingdom
16
December 2017
March 2018
October 2018
45
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.
May 10, 2019
August 7, 2019
September 18, 2023
Germany, Italy, Netherlands, Portugal, Spain, United States
40
18 Years to 75 Years (Adult, Older Adult), All Sexes, No Healthy Volunteers
Hepatitis B
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.
The purpose of this study is to evaluate the efficacy in terms of hepatitis B surface antigen (HBsAg) levels of the study intervention (that is, JNJ-73763989 + JNJ-56136379 + nucleos[t]ide analog [NA] and pegylated interferon alpha-2a [PegIFN-alpha2a]).
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.
The purpose of this study is to evaluate the efficacy of a treatment regimen of JNJ-73763989 + pegylated interferon alpha-2a (PegIFN-alpha-2a) + nucleos(t)ide analog (NA).
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.
The purpose of this study is to evaluate the efficacy of 48-week study intervention with JNJ-73763989+JNJ-56136379+nucleos(t)ide analog (NA) regimen compared to NA alone assessed by HBsAg levels. This study is part of HepB Wings Platform Trial (PLATFORMPAHPB2001).
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).
The purpose of this study is to assess changes in intrahepatic hepatitis B surface antigen (HBsAg) between baseline and on-treatment liver biopsy in response to JNJ-3989-based combination treatment.
The purpose of the study is to evaluate on-treatment efficacy against hepatitis D virus (HDV) of JNJ-73763989 + nucleos(t)ide analog (NA) regimen compared to NA alone.
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).
The purpose of this study is to establish the dose-response relationship for antiviral activity of 3 dose levels of JNJ-73763989+nucleos(t)ide analog (NA) and to evaluate the efficacy of combination regimens of JNJ-73763989+NA (with and without JNJ-56136379) and of JNJ-56136379+NA.
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).
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.
February 1, 2021
April 17, 2023
September 22, 2021
29
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.
September 14, 2020
February 13, 2024
54
N/A
July 20, 2020
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.
June 9, 2022
130
July 4, 2019
August 23, 2019
25
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.
March 11, 2021
January 9, 2024
24
18 Years to 65 Years (Adult, Older Adult)
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.
September 17, 2020
October 16, 2023
Study Completion Date
52
February 18, 2021
18 Years to 55 Years (Adult)
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.
March 29, 2021
April 26, 2022
471
April 2020
Australia, Hong Kong, New Zealand
114
18 Years to 65 Years (Adult, Older Adult), All Sexes, Accepts Healthy Volunteers
FSHD
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.
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.
November 15, 2023
January 2024
April 2025
June 2025
18 Years to 70 Years, All Sexes, No Healthy Volunteers
Myotonic Dystrophy Type 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.
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.
November 18, 2023
October 2025
18 Years to 65 Years, All Sexes, No Healthy Volunteers
Complement Mediated Disease
ARO-C3 is designed to reduce production of complement component 3 as a potential treatment for various complement mediated diseases.
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.
Australia, Georgia, Germany, Korea, New Zealand, Spain, Thailand, United Kingdom
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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