A Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients

NCT03780543 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ABI-H0731-211NCT03780543
• Study Type: interventional
• Target: 92
• Locations: 5 countries
• Sites: 24

Brief Summary

Open-label, extension study to evaluate the safety and efficacy of combination therapy and its effect on sustained viral response biomarkers.

Conditions

Chronic Hepatitis B

Keywords

CHB (chronic hepatitis B infection); HBV (hepatitis B virus); HBeAg positive (hepatitis B "e" antigen - positive); HBeAg negative (hepatitis B "e" antigen - negative); Hepatitis B (hepatitis B virus); Hepatitis B virus (HBV); SVR (sustained viral response)

Outcome Measures

Primary Outcomes (1)

• Sustained Viral Response (SVR) at 24 Weeks Off Treatment

  To evaluate the potential for combination therapy with ABI-H0731+ NrtI to increase SVR rates in subjects who have chronic hepatitis B (CHB). To evaluate the proportion of subjects who meet the definition of SVR at 24 weeks off treatment, the SVR rate and corresponding 95% confidence interval will be presented for the overall population while on combination therapy. SVR is defined as sustained viral response with HBV DNA , LOQ (20 IU/mL) through off-treatment Week 24.

  Completing from week 52 until week 76

Secondary Outcomes (4)

• Number of Subjects With Adverse Events

  Up to Week 148

• Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS)

  EOT: up to Week 52 or 148; EOS: up to 3 years off treatment

• Number of Subjects With Suppression/Loss of Viral HBeAg Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy

  upto Week 148

• Number of Subjects With Suppression/Loss of Viral Core-related Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy

  Up to Week 148

Study Arms (3)

HBeAg-negative Subjects from Parent Study ABI-H0731-201

ACTIVE COMPARATOR

Subjects who on Day 1 of parent study ABI-H0731-201 (NCT03576066) were standard of care (SOC) nucleos(t)ide (NrtI)-suppressed and HBeAg-negative will receive both ABI-H0731 + SOC NrtI for at least 52 weeks, after which time they will discontinue both ABI-H0731 and SOC NrtI and enter long-term off-treatment follow-up (FU) for up to 3 years.

Drug: standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)

HBeAg-positive Subjects from Parent Study ABI-H0731-201

ACTIVE COMPARATOR

Subjects who on Day 1 of parent study ABI-H0731-201 (NCT03576066) were SOC NrtI-suppressed and HBeAg-positive will receive ABI-H0731 + SOC NrtI for at least 52 weeks, after which time their viral response will be evaluated. 1. Subjects who meet the virologic response criteria will discontinue both ABI-H0731 and SOC NrtI and enter long-term off-treatment follow-up (FU) for up to 3 years. 2. Subjects with insufficient virologic response will discontinue ABI-H0731 only and continue on SOC NrtI alone and followed-up for 12 weeks.

Drug: standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)

Subjects from Parent Study ABI-H0731-202

ACTIVE COMPARATOR

Subjects who on Day 1 of parent study ABI-H0731-202 (NCT03577171) were treatment-naive and HBeAg-positive will receive ABI-H0731 + SOC NrtI for at least 52 weeks, after which time their viral response will be evaluated. 1. Subjects who meet the virologic response criteria at Week 52 will continue to receive ABI-H0731 + SOC NrtI for an additional 96 weeks, after which time their viral response will be evaluated at Week 148. Subjects who meet the virologic response criteria at Week 148 will discontinue both ABI-H0731 and SOC NrtI and enter long-term off-treatment follow-up for up to 3 years. Subjects with insufficient virologic response at Week 148, will discontinue ABI-H0731 only and continue on SOC NrtI alone for up to 12 weeks. 2. Subjects with insufficient virologic response at Week 52 will discontinue from ABI-H0731only and continue on SOC NrtI alone and enter follow-up for up to 12 weeks.

Drug: standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)

Interventions

standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI) DRUG

Participants will continue on their SOC NrtI, Entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF) or Tenofovir Alafenamide (TAF) tablet QD (once daily) orally as per approved package insert.

Also known as: Entecavir (ETV) - brand name Baraclude, Tenofovir Disoproxil Fumarate (TDF) - brand name: Viread, Tenofovir Alafenamide (TAF) - brand name: Descovy

HBeAg-negative Subjects from Parent Study ABI-H0731-201; HBeAg-positive Subjects from Parent Study ABI-H0731-201; Subjects from Parent Study ABI-H0731-202

Eligibility Criteria

• Age: 18 Years - 71 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent.
• Previously enrolled on Study ABI-H0731-201 (NCT03576066) or ABI-H0731-202 (NCT03577171) and completed the treatment period, with demonstrated compliance in the opinion of the investigator.
• Female subjects must agree to use an effective birth control method for the duration of the study and follow-up, or be surgically sterile for at least 6 months, or at least 2 years postmenopausal with serum follicle-stimulating hormone (FSH) levels consistent with a postmenopausal status. Effective birth control methods include male or female condom (may not be used together due to increased risk of breakage), vasectomy, intrauterine device (IUD), diaphragm, or cervical cap. Female subjects of childbearing potential must have a negative serum pregnancy test.
• All heterosexually active male subjects must agree to use an effective birth control method for the duration of the study and follow-up. Effective birth control methods include male or female condom (may not be used together due to increased risk of breakage), vasectomy, hormone-based contraception (only female partner of a male subject), IUD, diaphragm, or cervical cap.
• Agreement to adhere to Lifestyle Considerations (including abstaining from alcohol abuse \[defined as alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol)\] and the use of illicit substances, herbal or other substances, or unnecessary over-the-counter medications throughout study duration.
• In good general health except for chronic HBV infection.
• Have the ability to take oral medication and be willing to adhere to the ABI-H0731-211 regimen in the opinion of the Investigator.

You may not qualify if:

• Must not have had evidence of HBV resistance-associated variants (RAVs) or lack of compliance on a previous study of ABI H0731.
• Must not have had a treatment-emergent adverse event or laboratory abnormalities deemed clinically significant and possibly or probably related to drug while on a previous study of ABI-H0731, that in the opinion of the Investigator or the Sponsor makes the subject unsuitable for this study.
• Current 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 subject unsuitable for the study.
• Females who are lactating or pregnant or wish to become pregnant within the duration of the ABI-H0731-211 study.

Sponsors & Collaborators

• Assembly Biosciences: lead

Study Sites (24)

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Coalition of Inclusive Medicine

Los Angeles, California, 90057, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Research and Education

San Diego, California, 92115, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Digestive Disease Associates

Catonsville, Maryland, 21228, United States

Location

Infectious Disease Care

Hillsborough, New Jersey, 08844, United States

Location

Sing Chan, MD

Flushing, New York, 11355, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, 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

Toronto General Hospital

Toronto, Ontario, Canada

Location

University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

Location

Auckland Clinical Studies

Auckland, New Zealand

Location

Waikato Hospital

Hamilton, New Zealand

Location

King's College London

London, United Kingdom

Location

Related Publications (1)

• Yuen MF, Fung S, Ma X, Nguyen TT, Hassanein T, Hann HW, Elkhashab M, Nahass RG, Park JS, Jacobson IM, Ayoub WS, Han SH, Gane EJ, Zomorodi K, Yan R, Ma J, Knox SJ, Stamm LM, Bonacini M, Weilert F, Ramji A, Bennett M, Ravendhran N, Chan S, Dieterich DT, Kwo PY, Schiff ER, Bae HS, Lalezari J, Agarwal K, Sulkowski MS. Long-term open-label vebicorvir for chronic HBV infection: Safety and off-treatment responses. JHEP Rep. 2024 Jan 18;6(4):100999. doi: 10.1016/j.jhepr.2023.100999. eCollection 2024 Apr.

  PMID: 38510983 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

Standard of Care; entecavir; Tenofovir; tenofovir alafenamide

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Development Officer
• Organization: Assembly BioSciences Inc.

manderson@assemblybio.com

415-855-3006

Study Officials

• Michele Anderson

  Assembly Biosciences Inc.

  STUDY DIRECTOR

• M. F. Yuen, MD, PhD, DSc

  The University of Hong Kong

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 15, 2018
• First Posted: December 19, 2018
• Study Start: December 20, 2018
• Primary Completion: April 26, 2021
• Study Completion: April 26, 2021
• Last Updated: April 19, 2023
• Results First Posted: February 17, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); HK (1); US (17); GB (1); NZ (2)