A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors
- Registration Number
- NCT04454567
- Lead Sponsor
- Assembly Biosciences
- Brief Summary
This study will explore the safety and antiviral activity of ABI-H0731 when added to a nucleos(t)ide reverse transcriptase inhibitor (NrtI) in participants who are partially virologically suppressed.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2
- Body mass index (BMI) 18 to 36 kg/m^2 and a minimum body weight of 45 kg (inclusive)
- In good general health except for chronic hepatitis B (CHB)
- HBeAg positive or HBeAg negative chronic hepatitis B
- HBV DNA >LLOQ using a commercially available assay with LLOQ=20 IU/mL
- On a stable NrtI regimen (ETV, TDF or TAF) for more than 12 months
- Lack of cirrhosis or advanced liver disease
-
Current or prior treatment for CHB with lamivudine, telbivudine, adefovir, HBV core inhibitor, or previous treatment with an investigational agent for HBV infection
-
Presence of substitutions in the HBV polymerase coding region which may confer reduced susceptibility to NrtIs
-
Co-infection with human immunodeficiency virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, or hepatitis D virus
-
Females who are lactating or wish to become pregnant during the course of the trial
-
History or evidence of advanced liver disease or hepatic decompensation
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Clinically significant cardiac disease including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than CHB; endocrine disorder; autoimmune disorder; poorly controlled diabetes mellitus; neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment; ongoing infection or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that, in the opinion of the Investigator or the Sponsor, makes the subject unsuitable for trial participation
-
History of hepatocellular carcinoma (HCC)
-
Exclusionary laboratory parameters at Screening:
- Platelet count <100,000/mm^3
- Albumin <lower limit of normal
- Total bilirubin >1.2 × upper limit of normal (ULN)
- Direct bilirubin >1.2 × ULN
- ALT >10 × ULN
- Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, the participant is eligible if a hepatic imaging trial prior to initiation of study drug reveals no lesions indicative of possible HCC.
- International Normalized Ratio >1.5 × ULN
- Glomerular filtration rate <50 mL/min/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration equation
- Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABI-H0731 + SOC NrtI ABI-H0731 Participants with chronic hepatitis B virus (HBV) infection with partial virologic suppression on NrtI alone will receive ABI-H0731 300 mg once daily plus standard of care (SOC) NrtI for 96 weeks, followed by SOC NrtI alone for an additional 24 weeks (120 weeks total). ABI-H0731 + SOC NrtI NrtI Participants with chronic hepatitis B virus (HBV) infection with partial virologic suppression on NrtI alone will receive ABI-H0731 300 mg once daily plus standard of care (SOC) NrtI for 96 weeks, followed by SOC NrtI alone for an additional 24 weeks (120 weeks total). Placebo + SOC NrtI ABI-H0731 Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120. Placebo + SOC NrtI Placebo Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120. Placebo + SOC NrtI NrtI Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120.
- Primary Outcome Measures
Name Time Method Number of Participants With an Adverse Event Baseline and up to 5 months Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48 Week 48 Number of Participants With Premature Discontinuation of Treatment Baseline and up to 5 months Number of Participants With a Laboratory Abnormality Baseline and up to 5 months
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in log10 HBV DNA Baseline and up to 5 months Number of Participants With HBV DNA <LLOQ at Each Timepoint Baseline and up to 5 months Number of Participants With Normalized Alanine Aminotransferase (ALT) Baseline and up to 5 months Plasma Concentrations of ABI-H0731 Baseline and up to 5 months Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg) Baseline and up to 5 months Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg) Baseline and up to 5 months Plasma Concentrations of Entecavir Baseline and up to 5 months Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment Baseline and up to 5 months Number of Participants With HBV pgRNA <LLOQ Baseline and up to 5 months Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg) Baseline and up to 5 months Number of Participants With HBV DNA <Limit of Detection (LOD) Baseline and up to 5 months Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA) Baseline and up to 5 months
Trial Locations
- Locations (12)
Quest Clinical Research
🇺🇸San Francisco, California, United States
Asia Pacific Liver Center
🇺🇸Los Angeles, California, United States
Research and Education
🇺🇸San Diego, California, United States
Schiff Center for Liver Disease
🇺🇸Miami, Florida, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Infectious Disease Care
🇺🇸Hillsborough, New Jersey, United States
Northwell Health
🇺🇸Manhasset, New York, United States
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Institute of Human Virology
🇺🇸Baltimore, Maryland, United States
Office of X.M., MD
🇺🇸Philadelphia, Pennsylvania, United States
Auckland Clinical Studies
🇳🇿Grafton, Auckland, New Zealand