A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection
- Conditions
- Chronic Hepatitis B
- Interventions
- Registration Number
- NCT03576066
- Lead Sponsor
- Assembly Biosciences
- Brief Summary
The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) hepatitis B virus (HBV) nucleos(t)ide reverse transcriptase inhibitor (NUC) medication is safe and effective in participants with chronic hepatitis B virus infection (cHBV).
- Detailed Description
This is a Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Participants with cHBV.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 73
- Male or female between ages 18 and 70 years
- Virologically-suppressed (defined as HBV DNA ≤limit of quantitation (LOQ) for at least 6 months before screening on SOC NUC therapy
- HBeAg-positive or HBeAg-negative at screening
- In good general health except for cHBV
Key
-
Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV)
-
History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening
-
Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than HBV, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, 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 participant unsuitable for the study
-
Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening
-
History of hepatocellular carcinoma (HCC)
-
Females who are lactating or pregnant or wish to become pregnant are excluded from the study
-
Exclusionary laboratory parameters at screening include:
- Platelet count <100,000/mm3
- Albumin <lower limit of normal (LLN)
- Direct bilirubin >1.2×upper limit of normal (ULN)
- Alanine aminotransferase (ALT) >5×ULN at screening
- International Normalized Ratio (INR) >1.5×ULN
- Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABI-H0731 + SOC NUC ABI-H0731 Virologically suppressed participants will receive ABI-H0731 along with SOC NUC (ETV, TDF or TAF) tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. ABI-H0731 + SOC NUC SOC NUC Virologically suppressed participants will receive ABI-H0731 along with SOC NUC (ETV, TDF or TAF) tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary. Placebo + SOC NUC SOC NUC Virologically suppressed participants will receive matching placebo tablets and continue their SOC NUC (ETV, TDF or TAF) for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary. Placebo + SOC NUC Placebo Oral Tablet Virologically suppressed participants will receive matching placebo tablets and continue their SOC NUC (ETV, TDF or TAF) for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary.
- Primary Outcome Measures
Name Time Method Change in Mean log10 Serum HBeAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC Baseline to Week 24 Change in Mean log10 Serum HBsAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC Baseline to Week 24
- Secondary Outcome Measures
Name Time Method Number of Participants With One or More Abnormal Safety Laboratory Result Up to Week 36 Number of Participants With a Clinically-significant Electrocardiogram Abnormality Up to Week 24 Trough Levels of Entecavir (ETV) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 Trough Levels of Tenofovir Alafenamide (TAF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 Trough Levels of ABI-H0731 on ABI-H0731 + SOC NUC Therapy Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 Number of Participants With Premature Study Discontinuation Up to Follow-up (maximum up to Week 36) Number of Participants With a Clinically-significant Change in Vital Signs Baseline and up to Week 24 Vital signs assessed were body temperature, respiratory rate, and pulse rate
Number of Participants With One or More Adverse Events Up to Follow-up (maximum up to Week 36) Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + NUC Therapy as Compared With Placebo + NUC Therapy Baseline to Week 24 Abnormal ALT was defined as ≥1.25 x upper limit of normal (34 Units/L for female and 43 Units/L for male participants).
Trough Levels of Tenofovir Disoproxil Fumarate (TDF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24 Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + SOC NUC Therapy Baseline, Weeks 2, 4, 12, and 24 Trough to Peak Ratios of SOC NUC on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy Baseline, Weeks 2, 4, 12, and 24
Trial Locations
- Locations (21)
Digestive Disease Associates
🇺🇸Catonsville, Maryland, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Medical Associates Research Group
🇺🇸San Diego, California, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
NYU Langone Health
🇺🇸New York, New York, United States
Infectious Disease Care
🇺🇸Hillsborough, New Jersey, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Sing Chan, MD
🇺🇸Flushing, New York, United States
Xiaoli Ma, MD
🇺🇸Philadelphia, Pennsylvania, United States
Toronto Liver Center
🇨🇦Toronto, Canada
GI Research Institute
🇨🇦Vancouver, Canada
Auckland City Hospital
🇳🇿Auckland, New Zealand
Cedars-Sinai Medical Center
🇺🇸Beverly Hills, California, United States
Quest Clinical Research
🇺🇸San Francisco, California, United States
Asia Pacific Liver Center
🇺🇸Los Angeles, California, United States
Southern California Research Center
🇺🇸Coronado, California, United States
Research and Education
🇺🇸San Diego, California, United States
University of Miami Hospital and Clinics
🇺🇸Miami, Florida, United States
Toronto General Hospital
🇨🇦Toronto, Canada
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States