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

NCT ID: NCT03780543

Last Updated: 2023-04-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-20
• Study Completion Date: 2021-04-26

Brief Summary

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

Detailed Description

This is an open-label extension of parent studies ABI-H0731-201 (NCT03576066) and ABI-H0731-202 (NCT03577171). The extension study will assess the safety of long-term (up to 100 weeks of treatment in extension study ABI-H0731-211) combination therapy and its effect on biomarkers of sustained viral response (SVR) (NCT03780543).

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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.

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

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.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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.

Subjects from Parent Study ABI-H0731-202

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.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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.

Interventions

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

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.

Intervention Type: DRUG

Other Intervention Names

Entecavir (ETV) - brand name Baraclude; Tenofovir Disoproxil Fumarate (TDF) - brand name: Viread; Tenofovir Alafenamide (TAF) - brand name: Descovy

Eligibility Criteria

Inclusion Criteria

1. Willing and able to provide informed consent.

2. 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.

3. 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.

4. 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.

5. 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.

6. In good general health except for chronic HBV infection.

7. Have the ability to take oral medication and be willing to adhere to the ABI-H0731-211 regimen in the opinion of the Investigator.

Exclusion Criteria

1. Must not have had evidence of HBV resistance-associated variants (RAVs) or lack of compliance on a previous study of ABI H0731.

2. 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.

3. 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.

4. Females who are lactating or pregnant or wish to become pregnant within the duration of the ABI-H0731-211 study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 71 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assembly Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michele Anderson

Role: STUDY_DIRECTOR

Assembly Biosciences Inc.

M. F. Yuen, MD, PhD, DSc

Role: STUDY_CHAIR

The University of Hong Kong

Locations

Cedars-Sinai Medical Center

Beverly Hills, California, United States

Southern California Research Center

Coronado, California, United States

Coalition of Inclusive Medicine

Los Angeles, California, United States

University of California Los Angeles

Los Angeles, California, United States

Research and Education

San Diego, California, United States

Medical Associates Research Group

San Diego, California, United States

Quest Clinical Research

San Francisco, California, United States

Stanford University Medical Center

Stanford, California, United States

University of Miami Hospital and Clinics

Miami, Florida, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Digestive Disease Associates

Catonsville, Maryland, United States

Infectious Disease Care

Hillsborough, New Jersey, United States

Sing Chan, MD

Flushing, New York, United States

NYU Langone Health

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Xiaoli Ma, MD

Philadelphia, Pennsylvania, United States

GI Research Institute

Vancouver, British Columbia, Canada

Toronto Liver Center

Toronto, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

University of Hong Kong, Queen Mary Hospital

Hong Kong, , Hong Kong

Auckland Clinical Studies

Auckland, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

King's College London

London, , United Kingdom

Countries

United States; Canada; Hong Kong; New Zealand; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38510983 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NCT03780543

Identifier Type: REGISTRY

Identifier Source: secondary_id

ABI-H0731-211

Identifier Type: -

Identifier Source: org_study_id