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Trial record 1 of 1 for:    ABI-H2158 | Phase 2
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A Study of ABI-H2158-containing Regimens in Participants With Chronic Hepatitis B Virus Infection

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ClinicalTrials.gov Identifier: NCT04398134
Recruitment Status : Terminated (Study stopped due to a safety signal of drug-induced liver injury in subjects receiving 2158)
First Posted : May 21, 2020
Results First Posted : August 26, 2022
Last Update Posted : September 15, 2022
Sponsor:
Information provided by (Responsible Party):
Assembly Biosciences

Brief Summary:
This Phase 2a study will assess the safety, antiviral activity, and pharmacokinetics (PK) of ABI-H2158 administered once daily for up to 72 weeks in combination with entecavir (ETV) in participants with chronic hepatitis B virus (HBV) infection.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: ABI-H2158 Drug: Placebo Drug: Entecavir (ETV) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2a, Multicenter, Single-Blind, Placebo-Controlled, Multiple Cohort Study Evaluating ABI-H2158-Containing Regimens in Chronic Hepatitis B Infection
Actual Study Start Date : August 28, 2020
Actual Primary Completion Date : October 14, 2021
Actual Study Completion Date : December 28, 2021


Arm Intervention/treatment
Experimental: ABI-H2158 plus ETV
ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Drug: ABI-H2158
3 X 100 mg tablets for oral administration

Drug: Entecavir (ETV)
0.5 mg tablet for oral administration

Placebo Comparator: Placebo plus ETV
Placebo matching ABI-2158 300 mg tablet once daily for 72 weeks plus ETV 0.5 mg tablet once daily for 96 weeks
Drug: Placebo
Sugar pill manufactured to mimic the ABI-H2158 tablets

Drug: Entecavir (ETV)
0.5 mg tablet for oral administration




Primary Outcome Measures :
  1. Percentage of Participants With Adverse Events [ Time Frame: Up to 72 weeks ]
    Describes the number of participants with One or More Adverse Events while they were on treatment with the study drug.

  2. Percentage of Participants With Premature Treatment Discontinuation [ Time Frame: Up to 72 weeks ]
    Describes the number of participants who discontinued treatment with ABI-H2158/placebo prematurely.

  3. Change From Baseline in Mean log10 HBV DNA [ Time Frame: Baseline and Week 24 ]
    HBV DNA was measured by Cobas AmpliPrep/ Cobas TaqMan HBV Test v2.0 (LOD 10 IU/mL). The analysis of data was descriptive only.

  4. Percentage of Participants With Abnormal Laboratory Results [ Time Frame: Up to 72 weeks ]
    Severity grades were defined by Grading Scale for Severity of Adverse Events and Laboratory Abnormalities [The DAIDS Version 2.1]. For maximum postbaseline toxicity grade, the most severe graded abnormality from all tests was counted for each participant. For each individual laboratory test, the most severe graded abnormality for that test was counted for a participant. A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last dose of ABI-H2158/Placebo plus 28 days.


Secondary Outcome Measures :
  1. Trough Plasma Concentration of ABI-H2158 [ Time Frame: Predose on Day 1, Week 4, Week 48, and Week 72 ]
  2. Trough-to-Peak Plasma Concentration Ratio of ABI-H2158 [ Time Frame: Predose on Day 1 and Weeks 4, 48, and 72 and at pre-specified intervals after dosing on Day 1 and Weeks 2, 8, 12, 16, 20, 24, and 28 ]
  3. Trough Plasma Concentration of ETV [ Time Frame: Predose on Day 1, Week 4, Week 48, and Week 72 ]
  4. Trough-to-Peak Plasma Concentration Ratio of ETV [ Time Frame: Predose on Day 1 and Weeks 4, 48, and 72 and at pre-specified intervals after dosing on Day 1 and Weeks 2, 8, 12, 16, 20, 24, and 28 ]
  5. Change in Mean log10 HBV pgRNA From Baseline to Week 24 and at Each Timepoint for ABI-H2158+ETV and PBO+ETV [ Time Frame: up to Week 72 ]
  6. Number of Participants With Reduction in HBV DNA Below the Assay Lower Limit of Quantitation [ Time Frame: Up to 72 weeks ]
  7. Number of Participants With Reduction in HBV pgRNA Below the Assay Lower Limit of Quantitation [ Time Frame: Up to 72 weeks ]
  8. Change From Baseline in Serum HBV Surface Antigen (HBsAg) [ Time Frame: Baseline and up to 72 weeks ]
  9. Change From Baseline in Serum HBV "e" Antigen (HBeAg) [ Time Frame: Baseline and up to 72 weeks ]
  10. Change From Baseline in Serum HBV Core-related Antigen (HBcrAg) [ Time Frame: Baseline and up to 72 weeks ]
  11. Proportion of Subjects With Abnormal ALT at Baseline Who Have Normal ALT at Week 24 and at Each Timepoint on ABI-H2158+ETV and PBO+ETV [ Time Frame: Baseline and up to Week 24 ]
  12. Ncidence of HBV Variants With Reduced Susceptibility to ABI-H2158 [ Time Frame: Up to 72 weeks ]
  13. Change in Mean log10 HBV DNA for ABI-H2158+ETV and PBO+ETV at Each Timepoint [ Time Frame: up to 72 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body mass index of 18 - 36 kg/m^2 and body weight ≥45 kg
  • HBeAg ≥500 IU/mL at Screening
  • In good general health except for chronic HBV infection for ≥6 months documented, for example, by at least two measurements of HBsAg positivity and/or detectable HBV DNA ≥6 months apart
  • Lack of cirrhosis or advanced liver disease

Exclusion Criteria:

  • Prior treatment for chronic HBV infection with lamivudine, telbivudine, adefovir, standard of care nucleoside or nucleotide analogue (NrtI), HBV core inhibitors, or an investigational agent for HBV infection
  • History or evidence of advanced liver disease or hepatic decompensation (including jaundice, ascites, portal hypertension, gastrointestinal bleeding, esophageal varices, hepatic encephalopathy)
  • History or presence of clinically significant medical conditions requiring frequent medical management or pharmacologic or surgical treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04398134


Locations
Show Show 44 study locations
Sponsors and Collaborators
Assembly Biosciences
Investigators
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Study Director: Grace Wang Assembly Biosciences
  Study Documents (Full-Text)

Documents provided by Assembly Biosciences:
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Responsible Party: Assembly Biosciences
ClinicalTrials.gov Identifier: NCT04398134    
Other Study ID Numbers: ABI-H2158-201
2019-004902-85 ( EudraCT Number )
First Posted: May 21, 2020    Key Record Dates
Results First Posted: August 26, 2022
Last Update Posted: September 15, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assembly Biosciences:
HBV
hepatitis B
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
DNA Virus Infections
Entecavir
Antiviral Agents
Anti-Infective Agents