A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors

NCT04454567 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ABI-H0731-205UTN 1111-1251-7136
• Study Type: interventional
• Target: 2
• Locations: 3 countries
• Sites: 12

Brief Summary

This study will explore the safety and antiviral activity of ABI-H0731 when added to a nucleos(t)ide reverse transcriptase inhibitor (NrtI) in participants who are partially virologically suppressed.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (4)

• Number of Participants With an Adverse Event

  Baseline and up to 5 months

• Number of Participants With Premature Discontinuation of Treatment

  Baseline and up to 5 months

• Number of Participants With a Laboratory Abnormality

  Baseline and up to 5 months

• Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48

  Week 48

Secondary Outcomes (12)

• Mean Change From Baseline in log10 HBV DNA

  Baseline and up to 5 months

• Number of Participants With HBV DNA <LLOQ at Each Timepoint

  Baseline and up to 5 months

• Number of Participants With HBV DNA <Limit of Detection (LOD)

  Baseline and up to 5 months

• Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)

  Baseline and up to 5 months

• Number of Participants With HBV pgRNA <LLOQ

  Baseline and up to 5 months

Study Arms (2)

ABI-H0731 + SOC NrtI

EXPERIMENTAL

Participants with chronic hepatitis B virus (HBV) infection with partial virologic suppression on NrtI alone will receive ABI-H0731 300 mg once daily plus standard of care (SOC) NrtI for 96 weeks, followed by SOC NrtI alone for an additional 24 weeks (120 weeks total).

Drug: ABI-H0731; Drug: NrtI

Placebo + SOC NrtI

PLACEBO COMPARATOR

Participants with chronic HBV infection with partial virologic suppression on NrtI alone will receive placebo to ABI-H0731 once daily plus SOC NrtI for 48 weeks, followed by ABI-H0731 300 mg once daily plus SOC NrtI for Weeks 48 to 96, followed by SOC NrtI alone for Weeks 96 to 120.

Drug: ABI-H0731; Drug: Placebo; Drug: NrtI

Interventions

ABI-H0731 DRUG

Participants will receive ABI-H0731 tablets orally once daily

ABI-H0731 + SOC NrtI; Placebo + SOC NrtI

Placebo DRUG

Participants will receive placebo to ABI-H0731 tablets orally once daily

Placebo + SOC NrtI

NrtI DRUG

Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert

Also known as: Nucleos(t)ide reverse transcriptase inhibitor

ABI-H0731 + SOC NrtI; Placebo + SOC NrtI

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)
• In good general health except for chronic hepatitis B (CHB)
• HBeAg positive or HBeAg negative chronic hepatitis B
• HBV DNA \>LLOQ using a commercially available assay with LLOQ=20 IU/mL
• On a stable NrtI regimen (ETV, TDF or TAF) for more than 12 months
• Lack of cirrhosis or advanced liver disease

You may not qualify if:

• Current or prior treatment for CHB with lamivudine, telbivudine, adefovir, HBV core inhibitor, or previous treatment with an investigational agent for HBV infection
• Presence of substitutions in the HBV polymerase coding region which may confer reduced susceptibility to NrtIs
• Co-infection with human immunodeficiency virus, hepatitis A virus, hepatitis C virus, hepatitis E virus, or hepatitis D virus
• Females who are lactating or wish to become pregnant during the course of the trial
• History or evidence of advanced liver disease or hepatic decompensation
• Clinically significant cardiac disease including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than CHB; 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 trial participation
• History of hepatocellular carcinoma (HCC)
• Platelet count \<100,000/mm\^3
• Albumin \<lower limit of normal
• Total bilirubin \>1.2 × upper limit of normal (ULN)
• Direct bilirubin \>1.2 × ULN
• ALT \>10 × ULN
• Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is \>ULN but \<100 ng/mL, the participant is eligible if a hepatic imaging trial prior to initiation of study drug reveals no lesions indicative of possible HCC.
• International Normalized Ratio \>1.5 × ULN
• Glomerular filtration rate \<50 mL/min/1.73 m\^2 by Chronic Kidney Disease Epidemiology Collaboration equation

Sponsors & Collaborators

• Assembly Biosciences: lead

Study Sites (12)

Asia Pacific Liver Center

Los Angeles, California, 90057, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Research and Education

San Diego, California, 92115, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Schiff Center for Liver Disease

Miami, Florida, 33136, United States

Location

Institute of Human Virology

Baltimore, Maryland, 21201, United States

Location

Infectious Disease Care

Hillsborough, New Jersey, 08844, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

Office of X.M., MD

Philadelphia, Pennsylvania, 19107, United States

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Auckland Clinical Studies

Grafton, Auckland, 1010, New Zealand

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

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-H0731-205 was terminated early by the study Sponsor for strategic reasons to prioritize research and development efforts on finite and curative HBV therapies. At the time of early termination, only 2 participants were enrolled, both of which discontinued their assigned study treatment early due to the study being terminated early by the Sponsor. As a result, the primary outcome of number of participants with HBV DNA \<LLOQ at Week 48 could not be assessed.

Results Point of Contact

• Title: Executive Director of Clinical Operations
• Organization: Assembly Biosciences

Clinicaltrials@assemblybio.com

833-509-4583

Study Officials

• Steven Knox

  Assembly Biosciences

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: July 1, 2020
• Study Start: November 11, 2020
• Primary Completion: April 8, 2021
• Study Completion: April 8, 2021
• Last Updated: October 20, 2022
• Results First Posted: October 20, 2022

Record last verified: 2022-09

Locations

NZ (1); US (9); HK (2)