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

Primary Purpose

Chronic Hepatitis B

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ABI-H0731
Placebo
NrtI
Sponsored by
Assembly Biosciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

  • Exclusionary laboratory parameters at Screening:

    • 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
    • Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator.

Sites / Locations

  • Asia Pacific Liver Center
  • California Liver Research Institute
  • Research and Education
  • Quest Clinical Research
  • Schiff Center for Liver Disease
  • Institute of Human Virology
  • Infectious Disease Care
  • Northwell Health
  • Office of X.M., MD
  • Prince of Wales Hospital
  • Queen Mary Hospital
  • Auckland Clinical Studies

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ABI-H0731 + SOC NrtI

Placebo + SOC NrtI

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

Number of Participants With an Adverse Event
Number of Participants With Premature Discontinuation of Treatment
Number of Participants With a Laboratory Abnormality
Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48

Secondary Outcome Measures

Mean Change From Baseline in log10 HBV DNA
Number of Participants With HBV DNA <LLOQ at Each Timepoint
Number of Participants With HBV DNA <Limit of Detection (LOD)
Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)
Number of Participants With HBV pgRNA <LLOQ
Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg)
Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg)
Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg)
Number of Participants With Normalized Alanine Aminotransferase (ALT)
Plasma Concentrations of ABI-H0731
Plasma Concentrations of Entecavir
Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment

Full Information

First Posted
June 18, 2020
Last Updated
September 23, 2022
Sponsor
Assembly Biosciences
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1. Study Identification

Unique Protocol Identification Number
NCT04454567
Brief Title
A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors
Official Title
A Phase 2a, Multi-Center, Single-Blind, Placebo-Controlled Study Evaluating Treatment Intensification With ABI-H0731 in Subjects With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Terminated
Why Stopped
Study stopped due to a change in the Sponsor's overall development strategy from treatment of chronic disease to finite, curative treatments, and is based partially on the advice and feedback from experts and regulators.
Study Start Date
November 11, 2020 (Actual)
Primary Completion Date
April 8, 2021 (Actual)
Study Completion Date
April 8, 2021 (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
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
ABI-H0731 + SOC NrtI
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo + SOC NrtI
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ABI-H0731
Intervention Description
Participants will receive ABI-H0731 tablets orally once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive placebo to ABI-H0731 tablets orally once daily
Intervention Type
Drug
Intervention Name(s)
NrtI
Other Intervention Name(s)
Nucleos(t)ide reverse transcriptase inhibitor
Intervention Description
Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert
Primary Outcome Measure Information:
Title
Number of Participants With an Adverse Event
Time Frame
Baseline and up to 5 months
Title
Number of Participants With Premature Discontinuation of Treatment
Time Frame
Baseline and up to 5 months
Title
Number of Participants With a Laboratory Abnormality
Time Frame
Baseline and up to 5 months
Title
Number of Participants With HBV DNA <Lower Limit of Quantification (LLOQ) at Week 48
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in log10 HBV DNA
Time Frame
Baseline and up to 5 months
Title
Number of Participants With HBV DNA <LLOQ at Each Timepoint
Time Frame
Baseline and up to 5 months
Title
Number of Participants With HBV DNA <Limit of Detection (LOD)
Time Frame
Baseline and up to 5 months
Title
Mean Change From Baseline in log10 HBV Pregenomic RNA (pgRNA)
Time Frame
Baseline and up to 5 months
Title
Number of Participants With HBV pgRNA <LLOQ
Time Frame
Baseline and up to 5 months
Title
Mean Change From Baseline in log10 Serum Hepatitis B 'e' Antigen (HBeAg)
Time Frame
Baseline and up to 5 months
Title
Mean Change From Baseline in log10 Serum Hepatitis B Core-related Antigen (HBcrAg)
Time Frame
Baseline and up to 5 months
Title
Mean Change From Baseline in log10 Serum Hepatitis B Surface Antigen (HBsAg)
Time Frame
Baseline and up to 5 months
Title
Number of Participants With Normalized Alanine Aminotransferase (ALT)
Time Frame
Baseline and up to 5 months
Title
Plasma Concentrations of ABI-H0731
Time Frame
Baseline and up to 5 months
Title
Plasma Concentrations of Entecavir
Time Frame
Baseline and up to 5 months
Title
Incidence of HBV Variants Among Participants With Evidence of Non-response to Treatment
Time Frame
Baseline and up to 5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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) Exclusionary laboratory parameters at Screening: 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 Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Knox
Organizational Affiliation
Assembly Biosciences
Official's Role
Study Director
Facility Information:
Facility Name
Asia Pacific Liver Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Facility Name
California Liver Research Institute
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Research and Education
City
San Diego
State/Province
California
ZIP/Postal Code
92115
Country
United States
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Schiff Center for Liver Disease
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Institute of Human Virology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Infectious Disease Care
City
Hillsborough
State/Province
New Jersey
ZIP/Postal Code
08844
Country
United States
Facility Name
Northwell Health
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Office of X.M., MD
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Prince of Wales Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Auckland Clinical Studies
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1010
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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