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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03780543
• Other study ID #: ABI-H0731-211
• Status: Terminated
• Phase: Phase 2
• Start date: December 20, 2018
• Est. completion date: April 26, 2021

Study information

• Verified date: February 2023
• Source: Assembly Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, extension study to evaluate the safety and efficacy of combination therapy and its effect on sustained viral response biomarkers.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 92
• Est. completion date: April 26, 2021
• Est. primary completion date: April 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 71 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• standard of care (SOC) Nucleoside reverse transcriptase inhibitor (NrtI)
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.

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Liver Center	Toronto	Ontario
Canada	GI Research Institute	Vancouver	British Columbia
Hong Kong	University of Hong Kong, Queen Mary Hospital	Hong Kong
New Zealand	Auckland Clinical Studies	Auckland
New Zealand	Waikato Hospital	Hamilton
United Kingdom	King's College London	London
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Cedars-Sinai Medical Center	Beverly Hills	California
United States	Digestive Disease Associates	Catonsville	Maryland
United States	Southern California Research Center	Coronado	California
United States	Sing Chan, MD	Flushing	New York
United States	Infectious Disease Care	Hillsborough	New Jersey
United States	Coalition of Inclusive Medicine	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	University of Miami Hospital and Clinics	Miami	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Xiaoli Ma, MD	Philadelphia	Pennsylvania
United States	Medical Associates Research Group	San Diego	California
United States	Research and Education	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Assembly Biosciences

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Completing from week 52 until week 76
Secondary	Number of Subjects With Adverse Events	Incidence of treatment emergent adverse events (AEs)	Up to Week 148
Secondary	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	EOT: up to Week 52 or 148; EOS: up to 3 years off treatment
Secondary	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	upto Week 148
Secondary	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	Up to Week 148