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

A Multi-center, Open-label, Long-term Extension Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients

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

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)

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).

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GI Research Institute
  • Ontario
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Center
    • Toronto, Ontario, Canada
      • Toronto General Hospital
• Hong Kong
  • Hong Kong, Hong Kong
    • University of Hong Kong, Queen Mary Hospital
• New Zealand
  • Auckland, New Zealand
    • Auckland Clinical Studies
  • Hamilton, New Zealand
    • Waikato Hospital
• United Kingdom
  • London, United Kingdom
    • King's College London
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90057
      • Coalition of Inclusive Medicine
    • San Diego, California, United States, 92123
      • Medical Associates Research Group
    • San Diego, California, United States, 92115
      • Research and Education
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School Of Medicine
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • Infectious Disease Care
  • New York
    • Flushing, New York, United States, 11355
      • Sing Chan, MD
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Xiaoli Ma, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: 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.; Other Names: Entecavir (ETV) - brand name Baraclude; Tenofovir Disoproxil Fumarate (TDF) - brand name: Viread; Tenofovir Alafenamide (TAF) - brand name: Descovy
Active Comparator: 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.; 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.; 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); 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.; Other Names: Entecavir (ETV) - brand name Baraclude; Tenofovir Disoproxil Fumarate (TDF) - brand name: Viread; Tenofovir Alafenamide (TAF) - brand name: Descovy
Active Comparator: 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.; 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.; 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); 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.; Other Names: Entecavir (ETV) - brand name Baraclude; Tenofovir Disoproxil Fumarate (TDF) - brand name: Viread; Tenofovir Alafenamide (TAF) - brand name: Descovy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Adverse Events	Incidence of treatment emergent adverse events (AEs)	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)	To measure the number and proportion of subjects with abnormal ALT at baseline who have normal ALT at end of treatment (EOT) and end of study (EOS) To measure the number and proportion of subjects regardless of levels of ALT at baseline at EOT and 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	Incidence of subjects with suppression/loss of viral Hepatitis B "e" antigen (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	Incidence of subjects with suppression/loss of viral core-related antigen (HBcrAg) or DNA on combination treatment whose viral antigens rebound off treatment	Up to Week 148

Collaborators and Investigators

• Sponsor: Assembly Biosciences
• Investigators: Study Director: Michele Anderson, Assembly Biosciences Inc.; Study Chair: M. F. Yuen, MD, PhD, DSc, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2018
• Primary Completion (Actual): April 26, 2021
• Study Completion (Actual): April 26, 2021

Study Registration Dates

• First Submitted: December 15, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir; Reverse Transcriptase Inhibitors
• Other Study ID Numbers: ABI-H0731-211; NCT03780543 (Registry Identifier: ClinicalTrials.gov identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No