A Study Evaluating ABI-H0731-containing Regimens in Chinese Participants With Chronic Hepatitis B Virus Infection

NCT04781647 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: ABI-H0731-203
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to evaluate the safety, antiviral activity, and pharmacokinetics of ABI-H0731 in combination with entecavir (ETV) and with ETV plus pegylated-interferon alpha (Peg-IFNα) in Chinese participants with chronic hepatitis B virus infection (cHBV)

Conditions

Chronic Hepatitis B

Keywords

cHBV; HBV; vebicorvir; VBR

Outcome Measures

Primary Outcomes (3)

• Number of Participants With an Adverse Event

  Up to 60 weeks

• Number of Participants With Premature Discontinuation of Treatment

  Up to 60 weeks

• Number of Participants With a Laboratory Abnormality

  Up to 60 weeks

Secondary Outcomes (8)

• Mean Change From Baseline in HBV pgRNA

  Baseline and at pre-specified time points up to 60 weeks

• Mean Change From Baseline HBV DNA

  Baseline and at pre-specified time points up to 60 weeks

• Mean Change From Baseline in HBeAg

  Baseline and at pre-specified time points up to 60 weeks

• Mean Change From Baseline in HBcrAg

  Baseline and at pre-specified time points up to 60 weeks

• Mean Change From Baseline in HBsAg

  Baseline and at pre-specified time points up to 60 weeks

Study Arms (3)

ABI-H0731 + ETV

ACTIVE COMPARATOR

Participants with cHBV will receive ABI-H0731 with ETV for 48 weeks, followed by ETV alone for 12 weeks

Drug: ABI-H0731; Drug: ETV

ABI-H0731 + ETV + Peg-IFNα

EXPERIMENTAL

Participants with cHBV will receive ABI-H0731 with ETV and Peg-IFNα for 24 weeks, followed by ABI-H0731 with ETV for 24 weeks, followed by ETV alone for 12 weeks

Drug: ABI-H0731; Drug: ETV; Biological: Peg-IFNα

ETV + Peg-IFNα

ACTIVE COMPARATOR

Participants with cHBV will receive ETV and Peg-IFNα for 24 weeks, followed by ABI-H0731 with ETV for 24 weeks, followed by ETV alone for 12 weeks

Drug: ETV; Biological: Peg-IFNα

Interventions

ABI-H0731 DRUG

Participants will receive ABI-H0731 300 mg tablets orally once daily

Also known as: Vebicorvir

ABI-H0731 + ETV; ABI-H0731 + ETV + Peg-IFNα

ETV DRUG

Participants will receive ETV 0.5 mg tablets orally once daily

Also known as: Entecavir

ABI-H0731 + ETV; ABI-H0731 + ETV + Peg-IFNα; ETV + Peg-IFNα

Peg-IFNα BIOLOGICAL

Participants will receive Peg-IFNα with a starting dose of 180 µg solution by subcutaneous injection once weekly

Also known as: Pegylated-interferon Alpha

ABI-H0731 + ETV + Peg-IFNα; ETV + Peg-IFNα

Eligibility Criteria

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

You may qualify if:

• Body mass index (BMI) 18 to 36 kg/m\^2 and a minimum body weight of 45 kg (inclusive)
• Female subjects must be non-pregnant and have a negative serum pregnancy test
• Chronic hepatitis B infection, defined as HBV infection for ≥6 months documented, for example, by at least 2 measurements of HBsAg positivity and/or detectable HBV DNA ≥6 months apart (inclusive of Screening). For subjects without clear documentation of CHB, serum immunoglobulin M (IgM) antibody to the HBV core antigen (HBcAb) must be negative at Screening to exclude acute HBV infection.
• HBeAg positive with HBV DNA ≥2 × 10\^4 IU/mL at Screening
• Lack of cirrhosis or advanced liver disease
• A candidate for interferon-based therapy
• Agreement to comply with protocol-specified contraceptive requirements
• Agreement to abstain from alcohol abuse and the use of illicit substances from Screening through the duration of the study
• In good general health, except for cHBV, in the opinion of the Investigator
• Able to take oral medication and be willing to receive subcutaneous injections of Peg-IFNα.

You may not qualify if:

• Current or prior treatment for CHB with
• A nucleos(t)ide reverse transcriptase inhibitor of the HBV polymerase (NrtI) (ETV, tenofovir disoproxil fumarate or tenofovir alafenamide) for \>4 weeks at any time. Note, NrtI treatment of ≤4 weeks duration cannot be within 6 months prior to Screening
• Interferon-based therapy within 6 months prior to Screening
• Liver-protecting and/or ALT-lowering treatment including traditional Chinese medicine within 1 month of Screening
• Lamivudine, telbivudine or adefovir (of any duration)
• Previous treatment with siRNA within 9 months prior to Screening
• HBV core inhibitors (any duration)
• Previous treatment with any other investigational agent for HBV infection within 6 months prior to Screening
• Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV) hepatitis C virus (HCV), hepatitis E virus (HEV), or hepatitis D virus (HDV)
• Females who are lactating, or wish to become pregnant during the course of the study
• History or evidence of advanced liver disease or hepatic decompensation at any time prior to, or at the time of Screening
• History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
• Clinically significant psychiatric disease, including severe depression, history of suicidal ideation or suicide attempt
• Clinically significant cardiac disease including poorly controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than cHBV; 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 study participation
• History of hepatocellular carcinoma (HCC)

Sponsors & Collaborators

• Assembly Biosciences: lead

Study Sites (9)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Beijing YouAn Hospital, Capital Medical University

Beijing, Beijing Municipality, 100069, China

Location

Nanfang Hospital, First Military Medical University

Guangzhou, Guangdong, 510000, China

Location

8th Affiliated Hospital of Guangzhou

Guangzhou, Guangdong, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

Jilin University First Hospital

Changchun, Jilin, 130021, China

Location

Ruijin Hospital Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, 201508, China

Location

The first affiliated Hospital, College of Zhejiang University

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; 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

Limitations and Caveats

Study ABI-H0731-203 was terminated early by the study Sponsor for strategic reasons to prioritize research and development efforts on finite and curative HBV therapies. As a result, not all subjects completed Week 48 and some outcome measures were impacted.

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: Assembly BioSciences Inc.

psalstrand@assemblybio.com

415-366-5172

Study Officials

• Grace Wang, MD

  Assembly Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 4, 2021
• Study Start: February 18, 2021
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: October 6, 2023
• Results First Posted: October 6, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)