A Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)

NCT03577171 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ABI-H0731-202
• Study Type: interventional
• Target: 25
• Locations: 5 countries
• Sites: 12

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)

Conditions

Chronic Hepatitis B

Keywords

cHBV; HBV; HBeAg-positive; hepatitis B; vebicorvir; VBR

Outcome Measures

Primary Outcomes (1)

• 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

  Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL.

  Baseline, Week 12, and Week 24

Secondary Outcomes (13)

• Number of Participants One or More Adverse Events

  Up to Follow-up (maximum up to Week 36)

• Number of Participants With Premature Study Discontinuation

  Up to Follow-up (maximum up to Week 36)

• 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

• Number of Participants With a Clinically-significant Change in Vital Signs

  Baseline and up to Week 24

Study Arms (2)

ABI-H0731 + SOC ETV

EXPERIMENTAL

Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV 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.

Drug: ABI-H0731; Drug: SOC ETV

Placebo + SOC ETV

EXPERIMENTAL

Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally 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.

Drug: SOC ETV; Drug: Placebo Oral Tablet

Interventions

ABI-H0731 DRUG

Participants will receive 300mg QD of ABI-H0731 tablets orally.

ABI-H0731 + SOC ETV

SOC ETV DRUG

Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.

Also known as: Entecavir

ABI-H0731 + SOC ETV; Placebo + SOC ETV

Placebo Oral Tablet DRUG

Participants will receive matching QD placebo tablets orally.

Placebo + SOC ETV

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Assembly Biosciences: lead

Study Sites (12)

Southern California Research Center

Coronado, California, 92118, United States

Location

Asia Pacific Liver Center

Los Angeles, California, 90057, United States

Location

Research and Education

San Diego, California, 92105, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Xiaoli Ma MD

Philadelphia, Pennsylvania, 19107, United States

Location

GI Research Institute

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Toronto Liver Center

Toronto, Ontario, M6H 3M1, Canada

Location

University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

Location

Waikato Hospital

Hamilton, New Zealand

Location

King's College London

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35697332 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

entecavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Linda Baher, Sr. Director, Clinical Operations
• Organization: Assembly Biosciences

clinicaltrials@assemblybio.com

415-521-3808

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: July 5, 2018
• Study Start: June 19, 2018
• Primary Completion: June 21, 2019
• Study Completion: June 21, 2019
• Last Updated: January 28, 2021
• Results First Posted: January 28, 2021

Record last verified: 2021-01

Locations

HK (1); GB (1); CA (2); US (7); NZ (1)