Clinical trial NCT03577171: A Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)
Official title: A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Patients With Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: cHBV
HBV
HBeAg-positive
hepatitis B
vebicorvir
VBR
Lead sponsor: Assembly Biosciences
Sponsor class: INDUSTRY
First posted: 2018-07-05
Enrollment: 25
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) entecavir (ETV) is safe and effective in participants with chronic hepatitis B infection (cHBV)

Detailed description: This is a Phase 2a, multi-center, double-blind, placebo-controlled study evaluating ABI-H0731+ ETV vs ETV alone for the treatment of viremic hepatitis B "e" antigen (HBeAg)-positive participants with cHBV.

Eligibility criteria: Key Inclusion Criteria:

* Male or female between ages 18 and 70 years
* HBeAg-positive at screening
* In good general health except for cHBV
* HBV viral load ≥2×105 IU/mL
* Hepatitis B surface antigen (HBsAg) \>1000 IU/mL at screening

Key Exclusion Criteria:

* Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for \>4 weeks
* 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:

  * Platelet count \<100,000/mm3
  * Albumin \<lower limit of normal (LLN)
  * Direct bilirubin \>1.2×upper limit of normal (ULN)
  * Alanine aminotransferase (ALT) \>10×ULN at screening
  * Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is \>ULN but \<100 ng/mL, participant is eligible if a hepatic imaging study prior to the initiation of study drug reveals no lesions suspicious of possible HCC
  * 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 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV
timeFrame: Baseline, Week 12, and Week 24
Secondary outcomes:
measure: Number of Participants 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 + SOC ETV as Compared to Placebo + SOC ETV
timeFrame: Baseline to Week 24
measure: Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24
measure: Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24
measure: Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
timeFrame: Up to Week 36
measure: Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy
timeFrame: Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
measure: Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV 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 + ETV Therapy
timeFrame: Baseline, Weeks 2, 4, 12, and 24
measure: Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy
timeFrame: Baseline, Weeks 2, 4, 12, 24, and 28
Other outcomes:
Locations:
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: San Diego
country: United States
facility: Research and Education
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Philadelphia
country: United States
facility: Xiaoli Ma MD
state: Pennsylvania
city: Vancouver
country: Canada
facility: GI Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: Toronto Liver Center
state: Ontario
city: Hong Kong
country: Hong Kong
facility: University of Hong Kong, Queen Mary Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: London
country: United Kingdom
facility: King's College London
Study officials:
References:
citation: Sulkowski MS, 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, Yuen MF. Safety and efficacy of vebicorvir administered with entecavir in treatment-naive patients with chronic hepatitis B virus infection. J Hepatol. 2022 Nov;77(5):1265-1275. doi: 10.1016/j.jhep.2022.05.027. Epub 2022 Jun 11.