Clinical trial NCT03576066: A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection
Official title: A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Patients With Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Chronic hepatitis B
HBV
HBeAg-positive
hepatitis B
HBeAg-negative
vebicorvir
VBR
Lead sponsor: Assembly Biosciences
Sponsor class: INDUSTRY
First posted: 2018-07-03
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in Mean log10 Serum HBsAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC
timeFrame: Baseline to Week 24
measure: Change in Mean log10 Serum HBeAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Number of Participants With One or More Adverse Events
timeFrame: Up to Follow-up (maximum up to Week 36)
measure: Number of Participants With Premature Study Discontinuation
timeFrame: Up to Follow-up (maximum up to Week 36)
measure: Number of Participants With One or More Abnormal Safety Laboratory Result
timeFrame: Up to Week 36
measure: Number of Participants With a Clinically-significant Electrocardiogram Abnormality
timeFrame: Up to Week 24
measure: Number of Participants With a Clinically-significant Change in Vital Signs
timeFrame: Baseline and up to Week 24
measure: 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
timeFrame: Baseline to Week 24
measure: Trough Levels of ABI-H0731 on ABI-H0731 + SOC NUC Therapy
timeFrame: Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
measure: Trough Levels of Entecavir (ETV) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
timeFrame: Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
measure: Trough Levels of Tenofovir Alafenamide (TAF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
timeFrame: Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
measure: Trough Levels of Tenofovir Disoproxil Fumarate (TDF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
timeFrame: Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
measure: Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + SOC NUC Therapy
timeFrame: Baseline, Weeks 2, 4, 12, and 24
measure: Trough to Peak Ratios of SOC NUC on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
timeFrame: Baseline, Weeks 2, 4, 12, and 24
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Los Angeles
country: United States
facility: Asia Pacific Liver Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Diego
country: United States
facility: Research and Education
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Hospital and Clinics
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Catonsville
country: United States
facility: Digestive Disease Associates
state: Maryland
city: Hillsborough
country: United States
facility: Infectious Disease Care
state: New Jersey
city: Flushing
country: United States
facility: Sing Chan, MD
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Xiaoli Ma, MD
state: Pennsylvania
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Toronto
country: Canada
facility: Toronto Liver Center
city: Vancouver
country: Canada
facility: GI Research Institute
city: Auckland
country: New Zealand
facility: Auckland City Hospital
Study officials:
References:
citation: Yuen MF, Agarwal K, Ma X, Nguyen TT, Schiff ER, Hann HL, Dieterich DT, Nahass RG, Park JS, Chan S, Han SB, Gane EJ, Bennett M, Alves K, Evanchik M, Yan R, Huang Q, Lopatin U, Colonno R, Ma J, Knox SJ, Stamm LM, Bonacini M, Jacobson IM, Ayoub WS, Weilert F, Ravendhran N, Ramji A, Kwo PY, Elkhashab M, Hassanein T, Bae HS, Lalezari JP, Fung SK, Sulkowski MS. Safety and efficacy of vebicorvir in virologically suppressed patients with chronic hepatitis B virus infection. J Hepatol. 2022 Sep;77(3):642-652. doi: 10.1016/j.jhep.2022.04.005. Epub 2022 Apr 20.