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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 : January 6, 2020
Sponsor:
Information provided by (Responsible Party):
Assembly Biosciences

Brief Summary:
Open-label, extension study to evaluate the safety and efficacy of combination therapy and it's effect on sustained viral response biomarkers.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: ABI-H0731 Drug: SOC NUC Phase 2

Detailed Description:
This is an open-label extension protocol which will assess the safety of long-term (up to 24 months in total including the parent study) combination therapy and its effect on serum biomarkers of sustained virologic response (SVR) such as sustained clearance of serum HBV DNA, quantitative and qualitative reduction in the viral antigens hepatitis B "e" antigen (HBeAg), and hepatitis B surface antigen (HBsAg), as well as exploratory biomarkers such as reduction in circulating HBV RNA.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 20, 2018
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Entecavir

Arm Intervention/treatment
Active Comparator: Early Complete Responders

Subjects who on Day 1 have a 'complete response' will undergo a consolidation treatment period with ABI-H0731 + standard of care nucleos(t)ide (SOC NUC) for 28 weeks, after which time they will discontinue both their ABI-H0731 and SOC NUC. Subjects will continue to be intensively monitored for an additional 24 weeks of post-treatment follow-up to assess for a SVR. After post-treatment follow-up, subjects will continue to be monitored for an additional 24 months during a long-term, off-treatment follow-up period for a total of up to 36 months.

If subjects do not meet "complete response" criteria at Day 1, their Week 72 response will be evaluated at Week 76, as either a "late complete responder" or "all other subjects".

Drug: ABI-H0731
Participants will receive 300 mg QD of ABI-H0731 tablets orally.

Drug: SOC NUC
Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet QD orally as per approved package insert.
Other Name: Entecavir, tenofovir

Active Comparator: Late Complete Responders
Subjects who have met 'complete response' criteria by their Week 72 visit will continue combination therapy until Week 76, after which they will stop all HBV treatment (both ABI-H0731 + SOC NUC) and be monitored for an additional 24 weeks post-treatment follow-up to assess SVR at Week 100. Late Complete Responders will continue to be monitored during a long-term, off-treatment, follow-up period for up to 36 months.
Drug: ABI-H0731
Participants will receive 300 mg QD of ABI-H0731 tablets orally.

Drug: SOC NUC
Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet QD orally as per approved package insert.
Other Name: Entecavir, tenofovir

Active Comparator: All Other Subjects
Subjects who have not met "complete response" criteria by Week 72 (evaluated at Week 76) will continue combination therapy until Week 76, and will then stop therapy with ABI-H0731 and continue to be followed on their SOC NUC through Week 100.
Drug: ABI-H0731
Participants will receive 300 mg QD of ABI-H0731 tablets orally.

Drug: SOC NUC
Participants will continue on their SOC NUC (ETV, TDF or TAF) tablet QD orally as per approved package insert.
Other Name: Entecavir, tenofovir




Primary Outcome Measures :
  1. Number of subjects with sustained HBeAg loss (< 0.11 PEI units/mL) in HBeAg positive subjects [ Time Frame: Baseline to Week 76 or 100 ]
  2. Number of subjects with sustained viral suppression (below the limits of detection = 20 IU/mL) [ Time Frame: Baseline to Week 76 or 100 ]
  3. Number of subjects with loss or stable reduction of HBsAg to ≤ 100 IU/mL [ Time Frame: Baseline to Week 76 or 100 ]

Secondary Outcome Measures :
  1. 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 76 ]
  2. 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: Early Complete Responders: Baseline to Wk 28 (EOT), Month 36 (EOS); Late Complete Responders: Baseline to Wk 76 (EOT), Month 36 (EOS); All Other Subjects: Baseline to Wk 76 (EOT), Wk 100 (EOS); ]
  3. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 71 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide informed consent.
  2. Previously enrolled on a study of ABI-H0731 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.

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): NCT03780543


Locations
Show Show 24 study locations
Sponsors and Collaborators
Assembly Biosciences
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Responsible Party: Assembly Biosciences
ClinicalTrials.gov Identifier: NCT03780543    
Other Study ID Numbers: ABI-H0731-211
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: January 6, 2020
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
CHB
HBV
HBeAg positive
HBeAg negative
hepatitis B
hepatitis B virus
SVR
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Entecavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents