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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03780543
Recruitment Status : Active, not recruiting
First Posted : December 19, 2018
Last Update Posted : June 18, 2020
Sponsor:
Information provided by (Responsible Party):
Assembly Biosciences

Tracking Information
First Submitted Date  ICMJE December 15, 2018
First Posted Date  ICMJE December 19, 2018
Last Update Posted Date June 18, 2020
Actual Study Start Date  ICMJE December 20, 2018
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
Proportion of subjects with sustained viral response at 24 weeks off treatment [ Time Frame: Baseline to 24 weeks off treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2018)
  • Sustained HBeAg loss (< 0.11 PEI units/mL) in HBeAg positive subjects [ Time Frame: Baseline to Week 24 ]
  • Sustained viral suppression (below the limits of detection = 20 IU/mL) [ Time Frame: Baseline to Week 24 ]
  • Loss or stable reduction of HBsAg to ≤ 100 IU/mL [ Time Frame: Baseline to Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • Number of subjects with adverse events, premature discontinuations, abnormal safety laboratory results, abnormal electrocardiogram (ECG), or abnormal vital signs [ Time Frame: Up to Week 100 ]
  • Number of subjects with abnormal alanine aminotransferase (ALT) at Baseline who have normal ALT at end of treatment (EOT) and end of study (EOS) [ Time Frame: EOT: up to Week 52 or 100; EOS: up to 3 years off treatment ]
  • Number of subjects with suppression/loss of viral antigen/DNA on combination treatment whose viral antigens rebound off therapy [ Time Frame: Up to 3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2018)
  • Number of subjects with adverse events, premature discontinuations, abnormal safety laboratory results, abnormal electrocardiogram (ECG), or abnormal vital signs [ Time Frame: Up to maximum Week 52 ]
  • Number of subjects with abnormal alanine aminotransferase (ALT) at Baseline who have normal ALT at end of treatment (EOT) and end of study (EOS) [ Time Frame: Non Responders: Baseline to Wk 28 (EOT), Wk 40 (EOS); Early Complete Responders: Baseline to Wk 28 (EOT), Month 36 (EOS); Partial Responders: Baseline to Wk 52 (EOT), Wk 76 (EOS); Late Complete Responders: Baseline to Wk 52 (EOT), Month 36 (EOS) ]
  • Number of subjects with suppression/loss of viral antigen/DNA on combination treatment whose viral antigens rebound off therapy [ Time Frame: Up to 36 months following End of Treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients
Official Title  ICMJE A Multi-center, Open-label, Long-term Extension Study of ABI-H0731 + Nucleos(t)Ide as Finite Treatment for Chronic Hepatitis B Patients
Brief Summary Open-label, extension study to evaluate the safety and efficacy of combination therapy and it's 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis B
Intervention  ICMJE
  • Drug: ABI-H0731
    Participants will receive 300 mg QD of ABI-H0731 tablets orally.
  • Drug: SOC NrtI
    Participants will continue on their SOC NrtI (ETV, TDF or TAF) tablet QD orally as per approved package insert.
    Other Name: Entecavir, tenofovir
Study Arms  ICMJE
  • 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 nucleos(t)ide (SOC NrtI)-suppressed and HBeAg-negative will receive ABI-H0731 + SOC NrtI for at least 52 weeks, after which time they will discontinue both ABI-H0731 and SOC NrtI and be monitored for up to 3 years.
    Interventions:
    • Drug: ABI-H0731
    • Drug: SOC NrtI
  • 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 be monitored for up to 3 years. Subjects with insufficient virologic response will discontinue from ABI-H0731 and continue on SOC NrtI for 12 weeks.
    Interventions:
    • Drug: ABI-H0731
    • Drug: SOC NrtI
  • 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 48 weeks, after which time their viral response will be evaluated at Week 100. Subjects who meet the virologic response criteria at Week 100 will discontinue both ABI-H0731 and SOC NrtI and be monitored for up to 3 years, while those subjects with insufficient virologic response will discontinue from ABI-H0731 and continue on SOC NrtI for 12 weeks.

    Subjects with insufficient virologic response at Week 52 will discontinue from ABI-H0731 and continue on SOC NrtI for 12 weeks.

    Interventions:
    • Drug: ABI-H0731
    • Drug: SOC NrtI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 28, 2019)
92
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2018)
100
Estimated Study Completion Date  ICMJE June 2023
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 71 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Hong Kong,   New Zealand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03780543
Other Study ID Numbers  ICMJE ABI-H0731-211
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Assembly Biosciences
Study Sponsor  ICMJE Assembly Biosciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Assembly Biosciences
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP