Back to resultsA Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ABI-H0731
SOC ETV
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring cHBV, HBV, HBeAg-positive, hepatitis B, vebicorvir, VBR
Eligibility Criteria
Key Inclusion Criteria:
- Male or female between ages 18 and 70 years
- HBeAg-positive at screening
- In good general health except for cHBV
- HBV viral load ≥2×105 IU/mL
- Hepatitis B surface antigen (HBsAg) >1000 IU/mL at screening
Key Exclusion Criteria:
- Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for >4 weeks
- 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:
- Platelet count <100,000/mm3
- Albumin <lower limit of normal (LLN)
- Direct bilirubin >1.2×upper limit of normal (ULN)
- Alanine aminotransferase (ALT) >10×ULN at screening
- Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, participant is eligible if a hepatic imaging study prior to the initiation of study drug reveals no lesions suspicious of possible HCC
- 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
- Southern California Research Center
- Asia Pacific Liver Center
- Research and Education
- Quest Clinical Research
- Johns Hopkins University School of Medicine
- NYU Langone Health
- Xiaoli Ma MD
- GI Research Institute
- Toronto Liver Center
- University of Hong Kong, Queen Mary Hospital
- Waikato Hospital
- King's College London
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ABI-H0731 + SOC ETV
Placebo + SOC ETV
Arm Description
Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV 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.
Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally 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 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV
Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL.
Secondary Outcome Measures
Number of Participants 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 + SOC ETV as Compared to Placebo + SOC ETV
Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
HBV DNA was measured using COBAS TaqMan Version 2.0. The LLOQ was 20 IU/mL and the LOD was 10 IU/mL. The number of participants with HBV DNA below the limit of quantitation (<20 IU/mL) and target detected (≥10 IU/mL) was assessed.
Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV
Median time to viral suppression will be calculated and evaluated between participants on ABI-H0731 + ETV as compared to placebo + ETV.
Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
Emergence of a resistant HBV variant was defined as an increase of ≥1 log10 IU/mL from the nadir in HBV DNA.
Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy
Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy
Trough to Peak Ratios of ABI-H0731 on ABI-H0731 + ETV Therapy
Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03577171
Brief Title
A Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)
Official Title
A Phase 2a, Multi-center, Double-blind, Placebo-controlled Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Patients With Chronic Hepatitis B
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
June 19, 2018 (Actual)
Primary Completion Date
June 21, 2019 (Actual)
Study Completion Date
June 21, 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) entecavir (ETV) is safe and effective in participants with chronic hepatitis B infection (cHBV)
Detailed Description
This is a Phase 2a, multi-center, double-blind, placebo-controlled study evaluating ABI-H0731+ ETV vs ETV alone for the treatment of viremic hepatitis B "e" antigen (HBeAg)-positive 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
cHBV, HBV, HBeAg-positive, hepatitis B, vebicorvir, VBR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABI-H0731 + SOC ETV
Arm Type
Experimental
Arm Description
Participants with cHBV who are currently not being treated will receive ABI-H0731 along with SOC ETV 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 ETV
Arm Type
Experimental
Arm Description
Participants with cHBV who are currently not being treated will receive matching placebo along with SOC ETV tablets orally 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 300mg QD of ABI-H0731 tablets orally.
Intervention Type
Drug
Intervention Name(s)
SOC ETV
Other Intervention Name(s)
Entecavir
Intervention Description
Participants will receive SOC ETV (0.5 mg QD) orally as per approved package insert.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Participants will receive matching QD placebo tablets orally.
Primary Outcome Measure Information:
Title
Change in Mean log10 HBV DNA From Baseline (Day 1) to Week 12 or Week 24 on ABI H0731 + SOC ETV as Compared to Placebo + SOC ETV
Description
Hepatitis B virus (HBV) DNA was measured using COBAS TaqMan Version 2.0. The lower limit of quantitation (LLOQ) was 20 IU/mL and the limit of detection (LOD) was 10 IU/mL.
Time Frame
Baseline, Week 12, and Week 24
Secondary Outcome Measure Information:
Title
Number of Participants 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 + SOC ETV as Compared to Placebo + SOC ETV
Time Frame
Baseline to Week 24
Title
Number of Participants With a Decline in Viral DNA to Below Limit of Quantitation on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
Description
HBV DNA was measured using COBAS TaqMan Version 2.0. The LLOQ was 20 IU/mL and the LOD was 10 IU/mL. The number of participants with HBV DNA below the limit of quantitation (<20 IU/mL) and target detected (≥10 IU/mL) was assessed.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24
Title
Median Time to Viral Suppression, Defined as HBV DNA <20 IU/mL, on ABI-H0731 + ETV as Compared to Placebo + ETV
Description
Median time to viral suppression will be calculated and evaluated between participants on ABI-H0731 + ETV as compared to placebo + ETV.
Time Frame
Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24
Title
Number of Participants With Emergence of Resistant HBV Variants on ABI-H0731 + SOC ETV as Compared to Placebo + SOC ETV
Description
Emergence of a resistant HBV variant was defined as an increase of ≥1 log10 IU/mL from the nadir in HBV DNA.
Time Frame
Up to Week 36
Title
Trough Levels of ABI-H0731 on ABI-H0731 + SOC ETV Therapy
Time Frame
Before dosing at Baseline (Day 1), Weeks 2, 4, 12, and 24
Title
Trough Levels of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV 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 + ETV Therapy
Time Frame
Baseline, Weeks 2, 4, 12, and 24
Title
Trough to Peak Ratios of ETV on ABI-H0731 + ETV Therapy as Compared With Placebo + ETV Therapy
Time Frame
Baseline, Weeks 2, 4, 12, 24, and 28
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
HBeAg-positive at screening
In good general health except for cHBV
HBV viral load ≥2×105 IU/mL
Hepatitis B surface antigen (HBsAg) >1000 IU/mL at screening
Key Exclusion Criteria:
Any prior treatment with lamivudine or telbivudine, previous treatment with an investigational agent for HBV other than ABI-H0731; or any other SOC treatment for >4 weeks
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:
Platelet count <100,000/mm3
Albumin <lower limit of normal (LLN)
Direct bilirubin >1.2×upper limit of normal (ULN)
Alanine aminotransferase (ALT) >10×ULN at screening
Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100 ng/mL, participant is eligible if a hepatic imaging study prior to the initiation of study drug reveals no lesions suspicious of possible HCC
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
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
Research and Education
City
San Diego
State/Province
California
ZIP/Postal Code
92105
Country
United States
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
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
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Xiaoli Ma MD
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
GI Research Institute
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
Facility Name
Toronto Liver Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada
Facility Name
University of Hong Kong, Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Waikato Hospital
City
Hamilton
Country
New Zealand
Facility Name
King's College London
City
London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
35697332
Citation
Sulkowski MS, 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, Yuen MF. Safety and efficacy of vebicorvir administered with entecavir in treatment-naive patients with chronic hepatitis B virus infection. J Hepatol. 2022 Nov;77(5):1265-1275. doi: 10.1016/j.jhep.2022.05.027. Epub 2022 Jun 11.
Results Reference
derived
Learn more about this trial
A Study Evaluating ABI-H0731+ Entecavir vs Entecavir Alone for the Treatment of Viremic HBeAg-positive Participants With Chronic Hepatitis B Virus Infection (cHBV)
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