Open-Label Study of AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a in Subjects With Chronic Hepatitis B Infection
- Conditions
- Chronic Hepatitis b
- Interventions
- Drug: Peg-IFNα-2a
- Registration Number
- NCT04980482
- Lead Sponsor
- Arbutus Biopharma Corporation
- Brief Summary
This is a randomized, open label, multicenter Phase 2 study investigating the safety and antiviral activity of AB-729 in combination with ongoing NA therapy and short courses of Peg-IFNα-2a in subjects with CHB.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 43
- Chronic hepatitis B virus infection with documentation at least 6 months prior to screening
- Subjects must have been receiving either TAF, TDF (or equivalent), or ETV consistently for ≥12 months prior to dosing Day 1
- HBV DNA <LLOQ at Screening
- HBsAg between 100 and 5,000 IU/mL at Screening
- Subjects must be HBeAg-negative at Screening
- Fibroscan® result of ≤8.5 kPa within 6 months prior to dosing Day 1
- Medically stable based on physical examination, medical history, vital signs, laboratory values, and 12-lead Electrocardiogram (ECG) at screening
- Evidence of co-infection with hepatitis A, C, D or E virus or human immunodeficiency virus (HIV) at screening
- History of any clinically significant medical condition associated with chronic liver disease, cirrhosis, evidence of decompensated liver disease, or findings suggestive of hepatocellular carcinoma (HCC) at any time
- Contraindications to the use of Peg-IFNα-2a or incapable of self-administration or assisted administration of Peg-IFNα-2a
- Previous treatment with an experimental HBV-directed RNA-interference or antisense oligonucleotide product.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B, Group 1 AB-729 AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks. Cohort A, Group 1 AB-729 AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks. Cohort A, Group 1 Peg-IFNα-2a AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks. Cohort A, Group 2 AB-729 AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks. Cohort A, Group 2 Peg-IFNα-2a AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 24 weeks. Cohort B, Group 1 Peg-IFNα-2a AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: AB-729 60 mg SC every 8 weeks + NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks. Cohort B, Group 2 AB-729 AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks. Cohort B, Group 2 Peg-IFNα-2a AB-729 60 mg SC every 8 weeks + NA for 24 weeks, then randomized to: NA + Peg-IFNα-2a 180 mcg SC every week for 12 weeks.
- Primary Outcome Measures
Name Time Method The frequency and severity of treatment emergent adverse events (TEAEs), discontinuations due to adverse events (AEs), and laboratory abnormalities after dosing with AB-729 plus Peg-IFNα-2a Up to 124 weeks
- Secondary Outcome Measures
Name Time Method Change from baseline in HBsAg and other virologic markers at each time point Up to 124 weeks Proportion of subjects who discontinue NA and subsequently restart NA therapy after meeting criteria Up to 124 weeks Proportion of subjects with HBsAb seroconversion at each timepoint Up to 124 weeks Proportion of subjects who are eligible to stop NA after Week 24 of follow up Up to 76 weeks Proportion of subjects who discontinue NA and subsequently meet protocol defined clinical relapse criteria. Proportion of subjects who discontinue NA and subsequently meet protocol defined viral relapse criteria Up to 124 weeks Post-dose plasma concentrations of AB-729 anti-sense (AS), AB-729 AS(N-1)3', and AB-729 AS(N-2)3' at selected timepoints Up to 40 weeks
Trial Locations
- Locations (16)
Arizona Liver Health
🇺🇸Tucson, Arizona, United States
Research and Education, Inc.
🇺🇸San Diego, California, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
ID Care
🇺🇸Hillsborough, New Jersey, United States
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
St Vincent's Hospital Melbourne
🇦🇺Melbourne, Victoria, Australia
Prince of Wales Hospital, The Chinese University of Hong Kong
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Pusan National University Hospital
🇰🇷Pusan, Republic of Korea, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Arensia Exploratory Medicine Moldova
🇲🇩Chisinau, Moldova, Republic of
Chia-Yi Christian Hospital
🇨🇳Chiayi City, Taiwan
Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Medical Center of Limited Liability Company Harmoniya Krasy
🇺🇦Kyiv, Ukraine