Open-Label Study of AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a in Subjects With Chronic Hepatitis B Infection

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Open-Label, Multicenter Study Investigating AB-729, Nucleos(t)Ide Analogue and Pegylated Interferon Alfa-2a Treatment in Subjects With Chronic Hepatitis B Infection

Conditions
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Chronic Hepatitis b

Intervention / Treatment
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* Drug: AB-729
* Drug: Peg-IFNα-2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A, Group 1<br>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. | Drug: AB-729<br>* subcutaneous injection<br>Drug: Peg-IFNα-2a<br>* subcutaneous injection<br>* Other names: pegylated interferon alpha 2a;|
| Experimental: Cohort A, Group 2<br>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. | Drug: AB-729<br>* subcutaneous injection<br>Drug: Peg-IFNα-2a<br>* subcutaneous injection<br>* Other names: pegylated interferon alpha 2a;|
| Experimental: Cohort B, Group 1<br>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. | Drug: AB-729<br>* subcutaneous injection<br>Drug: Peg-IFNα-2a<br>* subcutaneous injection<br>* Other names: pegylated interferon alpha 2a;|
| Experimental: Cohort B, Group 2<br>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. | Drug: AB-729<br>* subcutaneous injection<br>Drug: Peg-IFNα-2a<br>* subcutaneous injection<br>* Other names: pegylated interferon alpha 2a;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HBsAg and other virologic markers at each time point |  | 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 restart NA therapy after meeting criteria |  | Up to 124 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B virus, Chronic hepatitis B, HBV, Hepatitis, CHB