Clinical trial NCT03780543: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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)
Lead sponsor: Assembly Biosciences
Sponsor class: INDUSTRY
First posted: 2018-12-19
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 71
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Sustained Viral Response (SVR) at 24 Weeks Off Treatment
timeFrame: Completing from week 52 until week 76
Secondary outcomes:
measure: Number of Subjects With Adverse Events
timeFrame: Up to Week 148
measure: Number of Subjects With Abnormal Alanine Aminotransferase (ALT) at Baseline Who Have Normal ALT at End of Treatment (EOT) and End of Study (EOS)
timeFrame: EOT: up to Week 52 or 148; EOS: up to 3 years off treatment
measure: Number of Subjects With Suppression/Loss of Viral HBeAg Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy
timeFrame: upto Week 148
measure: Number of Subjects With Suppression/Loss of Viral Core-related Antigen/DNA on Combination Treatment Whose Viral Antigens Rebound Off Therapy
timeFrame: Up to Week 148
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Coronado
country: United States
facility: Southern California Research Center
state: California
city: Los Angeles
country: United States
facility: Coalition of Inclusive Medicine
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Diego
country: United States
facility: Research and Education
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Hospital and Clinics
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Catonsville
country: United States
facility: Digestive Disease Associates
state: Maryland
city: Hillsborough
country: United States
facility: Infectious Disease Care
state: New Jersey
city: Flushing
country: United States
facility: Sing Chan, MD
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Xiaoli Ma, MD
state: Pennsylvania
city: Vancouver
country: Canada
facility: GI Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: Toronto Liver Center
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Hong Kong
country: Hong Kong
facility: University of Hong Kong, Queen Mary Hospital
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: London
country: United Kingdom
facility: King's College London
Study officials:
affiliation: Assembly Biosciences Inc.
name: Michele Anderson
role: STUDY_DIRECTOR
affiliation: The University of Hong Kong
name: M. F. Yuen, MD, PhD, DSc
role: STUDY_CHAIR
References: