A Study Evaluating Treatment Regimens Containing Vebicorvir (ABI-H0731) in Participants With Chronic Hepatitis B Infection

NCT ID: NCT04820686

Last Updated: 2023-11-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-07
• Study Completion Date: 2023-03-30

Brief Summary

The purpose of this study is to determine if vebicorvir (VBR, ABI-H0731) in combination with AB-729 is safe and effective in participants with chronic hepatitis B infection (cHBV) receiving a standard of care nucleos(t)ide/reverse transcriptase inhibitor (SOC NrtI).

Detailed Description

The initial cohort of participants will be enrolled in 3 treatment groups receiving 1) VBR + AB-729 + SOC NrtI, 2) VBR + SOC NrtI, or 3) AB-729 + SOC NrtI for up to 48 weeks. At Week 48, all participants will have an assessment of Treatment Stopping Criteria. Any participant who meets the Treatment Stopping Criteria, will discontinue their assigned treatment including NrtI and will remain in follow-up through Week 96. The participants who do not meet the Treatment Stopping Criteria will continue treatment with NrtI alone and will remain in follow-up through Week 96. Up to an additional 2 cohorts may be added to the study in future protocol amendments.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VBR + AB-729 + SOC NrtI

Participants with cHBV received VBR + AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up.

Group Type: EXPERIMENTAL

VBR

Intervention Type: DRUG

VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).

AB-729

Intervention Type: DRUG

AB-729 is a small interfering ribonucleic acid (siRNA) inhibitor of HBV. Participants will receive a 60-mg subcutaneous injection of AB-729 once every 8 weeks.

SOC NrtI

Intervention Type: DRUG

Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.

VBR + SOC NrtI

Participants with cHBV received VBR + SOC NrtI for 48 weeks followed by 48 weeks in follow-up. This treatment was used as a reference regimen.

Group Type: OTHER

VBR

Intervention Type: DRUG

VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).

SOC NrtI

Intervention Type: DRUG

Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.

AB-729 + SOC NrtI

Participants with cHBV received AB-729 + SOC NrtI for 48 weeks followed by 48 weeks in follow-up. This treatment was used as a reference regimen.

Group Type: OTHER

AB-729

Intervention Type: DRUG

AB-729 is a small interfering ribonucleic acid (siRNA) inhibitor of HBV. Participants will receive a 60-mg subcutaneous injection of AB-729 once every 8 weeks.

SOC NrtI

Intervention Type: DRUG

Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.

Interventions

VBR

VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).

Intervention Type: DRUG

AB-729

AB-729 is a small interfering ribonucleic acid (siRNA) inhibitor of HBV. Participants will receive a 60-mg subcutaneous injection of AB-729 once every 8 weeks.

Intervention Type: DRUG

SOC NrtI

Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.

Intervention Type: DRUG

Other Intervention Names

Vebicorvir, ABI-H0731; Entecavir (ETV); Tenofovir disoproxil fumarate (TDF); Tenofovir alafenamide (TAF)

Eligibility Criteria

Inclusion Criteria

• Body mass index (BMI) 18 to 36 kg/m^2 and a minimum body weight of 45 kg (inclusive)
• Female participants must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1
• Chronic Hepatitis B defined as HBV infection documented for ≥6 months prior to Screening
• Hepatitis B 'e' antigen (HBeAg) negative at least 3 months prior to Screening Visit (historical documentation) AND at the Screening Visit
• Virologically suppressed on SOC NrtI therapy with nonquantifiable HBV DNA for at least 6 months prior to Screening
• On a stable SOC NrtI regimen of ETV, TDF, or TAF for >12 months
• HBsAg ≥100 international units/mL at Screening
• Lack of bridging fibrosis or cirrhosis
• Agreement to comply with protocol-specified contraceptive requirements
• In good general health, except for cHBV, in the opinion of the Investigator
• Able to take oral medication and willing to receive subcutaneous injections of AB-729.

Exclusion Criteria

• Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis D virus (HDV), acute hepatitis A virus (HAV), or acute hepatitis E virus (HEV)
• Females who are lactating or wish to become pregnant during the course of the study
• History of liver transplant or evidence of advanced liver disease, cirrhosis, or hepatic decompensation at any time prior to, or at the time of Screening
• History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
• Clinically significant diseases or conditions, such as cardiac disease, including poorly-controlled or unstable hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease; liver disease other than cHBV; endocrine disorder; autoimmune disorder; poorly controlled diabetes mellitus; neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment; ongoing infection 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 study participation
• History of hepatocellular carcinoma (HCC)
• History of malignancy other than HCC unless the subject's malignancy has been in complete remission off chemotherapy and without additional medical or surgical interventions during the 3 years before Screening
• History or presence at Screening of electrocardiogram (ECG) abnormalities deemed clinically significant, in the opinion of the Investigator
• History of hypersensitivity or idiosyncratic reaction to any components or excipients of the investigational drugs
• History of any significant food or drug-related allergic reactions such as anaphylaxis or Stevens-Johnson syndrome
• Exclusionary laboratory results at Screening:

1. Platelet count <100,000/mm^3

2. Albumin <3 g/dL

3. Direct bilirubin >1.2× upper limit of normal (ULN)

4. ALT ≥5× ULN

5. Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is > ULN but <100 ng/mL, the subject is eligible if hepatic imaging prior to initiation of study drug reveals no lesions indicative of possible HCC

6. International Normalized Ratio (INR) >1.5× ULN

7. Estimated creatinine clearance (CrCl) <50 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight at Screening

8. Any other laboratory abnormality deemed clinically significant by the Investigator

• Current or prior use of prohibited (per protocol) concomitant medications from 28 days prior to Day 1.
• Current or prior treatment for cHBV with:

• Lamivudine, telbivudine or adefovir (any duration)
• HBV core inhibitor (any duration)
• siRNA or other oligonucleotide therapeutic (any duration)
• Interferon in the 6 months prior to Screening
• Any investigational agent for cHBV in the 6 months prior to Screening.
• Participation in another clinical study of a drug or device whereby the last investigational drug/device administration is within 60 days or 5 half-lives prior to study start.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arbutus Biopharma Corporation

INDUSTRY

Sponsor Role: collaborator

Assembly Biosciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Saint Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Saint George Hospital - Australia

Kogarah, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Footscray Hospital

Footscray, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Melbourne Health

Parkville, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Diagnostic Consultative Center Aleksandrovska

Sofia, Sofia-Grad, Bulgaria

Acibadem City Clinic Tokuda Hospital

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment St. Ivan Rilski

Sofia, , Bulgaria

Nov Rehabilitatsionen Tsentar EOOD

Stara Zagora, , Bulgaria

Vancouver Infectious Disease Centre

Vancouver, British Columbia, Canada

Pacific Gastroenterology Associates

Vancouver, British Columbia, Canada

University Hospital - London Health Sciences Centre

London, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Toronto Liver Centre

Toronto, Ontario, Canada

Centre Hospitalier Université de Québec - Université Laval

Québec, , Canada

Auckland Clinical Studies

Auckland, , New Zealand

Wellington Regional Hospital

Wellington, , New Zealand

Countries

Australia; Bulgaria; Canada; New Zealand

References

Ligat G, Verrier ER, Nassal M, Baumert TF. Hepatitis B virus-host interactions and novel targets for viral cure. Curr Opin Virol. 2021 Aug;49:41-51. doi: 10.1016/j.coviro.2021.04.009. Epub 2021 May 22.

Reference Type: DERIVED

PMID: 34029994 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ABI-H0731-204

Identifier Type: -

Identifier Source: org_study_id