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A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ABI-H0731
SOC NUC
Placebo Oral Tablet
Sponsored by
Assembly Biosciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Chronic hepatitis B, HBV, HBeAg-positive, hepatitis B, HBeAg-negative, vebicorvir, VBR

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Male or female between ages 18 and 70 years
  • Virologically-suppressed (defined as HBV DNA ≤limit of quantitation (LOQ) for at least 6 months before screening on SOC NUC therapy
  • HBeAg-positive or HBeAg-negative at screening
  • In good general health except for cHBV

Key Exclusion Criteria:

  • Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV)
  • History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening
  • 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 participant unsuitable for the study
  • Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening
  • History of hepatocellular carcinoma (HCC)
  • Females who are lactating or pregnant or wish to become pregnant are excluded from the study

  • Exclusionary laboratory parameters at screening include:

    • Platelet count <100,000/mm3
    • Albumin <lower limit of normal (LLN)
    • Direct bilirubin >1.2×upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) >5×ULN at screening
    • International Normalized Ratio (INR) >1.5×ULN
    • Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

Sites / Locations

  • Cedars-Sinai Medical Center
  • Southern California Research Center
  • Asia Pacific Liver Center
  • University of California Los Angeles
  • Research and Education
  • Medical Associates Research Group
  • Quest Clinical Research
  • Stanford University Medical Center
  • University of Miami Hospital and Clinics
  • Johns Hopkins University School of Medicine
  • Digestive Disease Associates
  • Infectious Disease Care
  • Sing Chan, MD
  • NYU Langone Health
  • Icahn School of Medicine at Mount Sinai
  • Thomas Jefferson University Hospital
  • Xiaoli Ma, MD
  • Toronto General Hospital
  • Toronto Liver Center
  • GI Research Institute
  • Auckland City Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ABI-H0731 + SOC NUC

Placebo + SOC NUC

Arm Description

Virologically suppressed participants will receive ABI-H0731 along with SOC NUC (ETV, TDF or TAF) tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary.

Virologically suppressed participants will receive matching placebo tablets and continue their SOC NUC (ETV, TDF or TAF) for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary.

Outcomes

Primary Outcome Measures

Change in Mean log10 Serum HBsAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC
Change in Mean log10 Serum HBeAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC

Secondary Outcome Measures

Number of Participants With One or More Adverse Events
Number of Participants With Premature Study Discontinuation
Number of Participants With One or More Abnormal Safety Laboratory Result
Number of Participants With a Clinically-significant Electrocardiogram Abnormality
Number of Participants With a Clinically-significant Change in Vital Signs
Vital signs assessed were body temperature, respiratory rate, and pulse rate
Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + NUC Therapy as Compared With Placebo + NUC Therapy
Abnormal ALT was defined as ≥1.25 x upper limit of normal (34 Units/L for female and 43 Units/L for male participants).
Trough Levels of ABI-H0731 on ABI-H0731 + SOC NUC Therapy
Trough Levels of Entecavir (ETV) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
Trough Levels of Tenofovir Alafenamide (TAF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
Trough Levels of Tenofovir Disoproxil Fumarate (TDF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + SOC NUC Therapy
Trough to Peak Ratios of SOC NUC on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy

Full Information

First Posted
June 6, 2018
Last Updated
January 29, 2021
Sponsor
Assembly Biosciences
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1. Study Identification

Unique Protocol Identification Number
NCT03576066
Brief Title
A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection
Official Title
A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Patients With Chronic Hepatitis B
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
June 11, 2018 (Actual)
Primary Completion Date
July 5, 2019 (Actual)
Study Completion Date
July 5, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assembly Biosciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if ABI-H0731 given in combination with a standard of care (SOC) hepatitis B virus (HBV) nucleos(t)ide reverse transcriptase inhibitor (NUC) medication is safe and effective in participants with chronic hepatitis B virus infection (cHBV).
Detailed Description
This is a Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731 as Adjunctive Therapy in Virally-suppressed Participants with cHBV.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Chronic hepatitis B, HBV, HBeAg-positive, hepatitis B, HBeAg-negative, vebicorvir, VBR

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ABI-H0731 + SOC NUC
Arm Type
Experimental
Arm Description
Virologically suppressed participants will receive ABI-H0731 along with SOC NUC (ETV, TDF or TAF) tablets orally for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to continue open-label ABI-H0731 for up to an additional year if necessary.
Arm Title
Placebo + SOC NUC
Arm Type
Active Comparator
Arm Description
Virologically suppressed participants will receive matching placebo tablets and continue their SOC NUC (ETV, TDF or TAF) for 24 weeks. Eligible participants may enter a separate extension study after Week 24 to start treatment on open-label ABI-H0731 for up to a year if necessary.
Intervention Type
Drug
Intervention Name(s)
ABI-H0731
Intervention Description
Participants will receive ABI-H0731 300 mg tablets orally once daily (QD).
Intervention Type
Drug
Intervention Name(s)
SOC NUC
Other Intervention Name(s)
Entecavir (ETV), Tenofovir disoproxil fumarate (TDF), Tenofovir alafenamide (TAF)
Intervention Description
Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet orally as per approved package insert.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Participants will receive placebo matching ABI-0731 tablets orally QD.
Primary Outcome Measure Information:
Title
Change in Mean log10 Serum HBsAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC
Time Frame
Baseline to Week 24
Title
Change in Mean log10 Serum HBeAg From Baseline (Day 1) to Week 24 on ABI-H0731 + SOC NUC as Compared to Placebo + SOC NUC
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Number of Participants With One or More Adverse Events
Time Frame
Up to Follow-up (maximum up to Week 36)
Title
Number of Participants With Premature Study Discontinuation
Time Frame
Up to Follow-up (maximum up to Week 36)
Title
Number of Participants With One or More Abnormal Safety Laboratory Result
Time Frame
Up to Week 36
Title
Number of Participants With a Clinically-significant Electrocardiogram Abnormality
Time Frame
Up to Week 24
Title
Number of Participants With a Clinically-significant Change in Vital Signs
Description
Vital signs assessed were body temperature, respiratory rate, and pulse rate
Time Frame
Baseline and up to Week 24
Title
Number of Participants With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at Week 24 on ABI-H0731 + NUC Therapy as Compared With Placebo + NUC Therapy
Description
Abnormal ALT was defined as ≥1.25 x upper limit of normal (34 Units/L for female and 43 Units/L for male participants).
Time Frame
Baseline to Week 24
Title
Trough Levels of ABI-H0731 on ABI-H0731 + SOC NUC Therapy
Time Frame
Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Title
Trough Levels of Entecavir (ETV) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
Time Frame
Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Title
Trough Levels of Tenofovir Alafenamide (TAF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
Time Frame
Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Title
Trough Levels of Tenofovir Disoproxil Fumarate (TDF) on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
Time Frame
Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Title
Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + SOC NUC Therapy
Time Frame
Baseline, Weeks 2, 4, 12, and 24
Title
Trough to Peak Ratios of SOC NUC on ABI-H0731 + SOC NUC Therapy as Compared With Placebo + SOC NUC Therapy
Time Frame
Baseline, Weeks 2, 4, 12, and 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Male or female between ages 18 and 70 years Virologically-suppressed (defined as HBV DNA ≤limit of quantitation (LOQ) for at least 6 months before screening on SOC NUC therapy HBeAg-positive or HBeAg-negative at screening In good general health except for cHBV Key Exclusion Criteria: Co-infection with HIV, hepatitis C virus (HCV), hepatitis E virus (HEV) or hepatitis D virus (HDV) History or evidence of hepatic decompensation (including gastrointestinal bleeding or esophageal varices) at any time prior to or at time of screening 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 participant unsuitable for the study Previous treatment with an investigational agent for HBV other than ABI-H0731 in the last 6 months before screening History of hepatocellular carcinoma (HCC) Females who are lactating or pregnant or wish to become pregnant are excluded from the study Exclusionary laboratory parameters at screening include: Platelet count <100,000/mm3 Albumin <lower limit of normal (LLN) Direct bilirubin >1.2×upper limit of normal (ULN) Alanine aminotransferase (ALT) >5×ULN at screening International Normalized Ratio (INR) >1.5×ULN Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Southern California Research Center
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
Facility Name
Asia Pacific Liver Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research and Education
City
San Diego
State/Province
California
ZIP/Postal Code
92105
Country
United States
Facility Name
Medical Associates Research Group
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Miami Hospital and Clinics
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Digestive Disease Associates
City
Catonsville
State/Province
Maryland
ZIP/Postal Code
21228
Country
United States
Facility Name
Infectious Disease Care
City
Hillsborough
State/Province
New Jersey
ZIP/Postal Code
08844
Country
United States
Facility Name
Sing Chan, MD
City
Flushing
State/Province
New York
ZIP/Postal Code
11354
Country
United States
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Xiaoli Ma, MD
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Toronto General Hospital
City
Toronto
Country
Canada
Facility Name
Toronto Liver Center
City
Toronto
Country
Canada
Facility Name
GI Research Institute
City
Vancouver
Country
Canada
Facility Name
Auckland City Hospital
City
Auckland
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35460726
Citation
Yuen MF, Agarwal K, Ma X, Nguyen TT, Schiff ER, Hann HL, Dieterich DT, Nahass RG, Park JS, Chan S, Han SB, Gane EJ, Bennett M, Alves K, Evanchik M, Yan R, Huang Q, Lopatin U, Colonno R, Ma J, Knox SJ, Stamm LM, Bonacini M, Jacobson IM, Ayoub WS, Weilert F, Ravendhran N, Ramji A, Kwo PY, Elkhashab M, Hassanein T, Bae HS, Lalezari JP, Fung SK, Sulkowski MS. Safety and efficacy of vebicorvir in virologically suppressed patients with chronic hepatitis B virus infection. J Hepatol. 2022 Sep;77(3):642-652. doi: 10.1016/j.jhep.2022.04.005. Epub 2022 Apr 20.
Results Reference
derived

Learn more about this trial

A Study Evaluating ABI-H0731 as Adjunctive Therapy in Participants With Chronic Hepatitis B Infection

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