Back to resultsA Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients
Primary Purpose
Chronic Hepatitis B
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring 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)
Eligibility Criteria
Inclusion Criteria:
- Willing and able to provide informed consent.
- 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.
- 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.
- 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.
- 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.
- In good general health except for chronic HBV infection.
- 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:
- Must not have had evidence of HBV resistance-associated variants (RAVs) or lack of compliance on a previous study of ABI H0731.
- 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.
- 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.
- Females who are lactating or pregnant or wish to become pregnant within the duration of the ABI-H0731-211 study.
Sites / Locations
- Cedars-Sinai Medical Center
- Southern California Research Center
- Coalition of Inclusive Medicine
- 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
- GI Research Institute
- Toronto Liver Center
- Toronto General Hospital
- University of Hong Kong, Queen Mary Hospital
- Auckland Clinical Studies
- Waikato Hospital
- King's College London
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
HBeAg-negative Subjects from Parent Study ABI-H0731-201
HBeAg-positive Subjects from Parent Study ABI-H0731-201
Subjects from Parent Study ABI-H0731-202
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of Subjects With Adverse Events
Incidence of treatment emergent adverse events (AEs)
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03780543
Brief Title
A Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients
Official Title
A Multi-center, Open-label, Long-term Extension Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
December 20, 2018 (Actual)
Primary Completion Date
April 26, 2021 (Actual)
Study Completion Date
April 26, 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
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HBeAg-negative Subjects from Parent Study ABI-H0731-201
Arm Type
Active Comparator
Arm Description
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.
Arm Title
HBeAg-positive Subjects from Parent Study ABI-H0731-201
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Subjects from Parent Study ABI-H0731-202
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)
Other Intervention Name(s)
Entecavir (ETV) - brand name Baraclude, Tenofovir Disoproxil Fumarate (TDF) - brand name: Viread, Tenofovir Alafenamide (TAF) - brand name: Descovy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Sustained Viral Response (SVR) at 24 Weeks Off Treatment
Description
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.
Time Frame
Completing from week 52 until week 76
Secondary Outcome Measure Information:
Title
Number of Subjects With Adverse Events
Description
Incidence of treatment emergent adverse events (AEs)
Time Frame
Up to Week 148
Title
Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS)
Description
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
Time Frame
EOT: up to Week 52 or 148; EOS: up to 3 years off treatment
Title
Number of Subjects With Suppression/Loss of Viral HBeAg Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy
Description
Incidence of subjects with suppression/loss of viral Hepatitis B "e" antigen (HBeAg) antigen/DNA on combination treatment whose viral antigens rebound off therapy
Time Frame
upto Week 148
Title
Number of Subjects With Suppression/Loss of Viral Core-related Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy
Description
Incidence of subjects with suppression/loss of viral core-related antigen (HBcrAg) or DNA on combination treatment whose viral antigens rebound off treatment
Time Frame
Up to Week 148
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
71 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willing and able to provide informed consent.
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.
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.
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.
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.
In good general health except for chronic HBV infection.
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:
Must not have had evidence of HBV resistance-associated variants (RAVs) or lack of compliance on a previous study of ABI H0731.
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.
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.
Females who are lactating or pregnant or wish to become pregnant within the duration of the ABI-H0731-211 study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Anderson
Organizational Affiliation
Assembly Biosciences Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
M. F. Yuen, MD, PhD, DSc
Organizational Affiliation
The University of Hong Kong
Official's Role
Study Chair
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
Coalition of Inclusive Medicine
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
92115
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
11355
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
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
Toronto General Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
University of Hong Kong, Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Auckland Clinical Studies
City
Auckland
Country
New Zealand
Facility Name
Waikato Hospital
City
Hamilton
Country
New Zealand
Facility Name
King's College London
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients
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