Clinical trial NCT04820686: A Study Evaluating Treatment Regimens Containing Vebicorvir (ABI-H0731) in Participants With Chronic Hepatitis B Infection
Official title: A Randomized Phase 2a, Multicenter, Open-Label, Multiple-Cohort Study Evaluating Regimens Containing Vebicorvir in Subjects With Chronic Hepatitis B Virus Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: cHBV
HBV
hepatitis B
vebicorvir
VBR
AB-729
Lead sponsor: Assembly Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Arbutus Biopharma Corporation
First posted: 2021-03-29
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With One or More Adverse Events (AEs)
timeFrame: AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.
measure: Number of Participants With Premature Treatment Discontinuation Due to AEs
timeFrame: AEs were collected from the time of signing the informed consent until the final follow-up visit, up to 96 weeks.
measure: Number of Participants With One or More Abnormal Laboratory Result
timeFrame: Laboratory results were collected from the time of signing the informed consent until the study was early terminated, up to 96 weeks.
Secondary outcomes:
measure: Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) On-Treatment
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56.
measure: Number of Participants With Serum HBsAg Below the Lower Limit of Quantitation (<LLOQ)
timeFrame: Pre-specified time points up to 96 weeks
measure: Number of Participants With HBV Deoxyribonucleic Acid (DNA) Not Detected (<5 IU/mL)
timeFrame: Week 48
measure: Number of Participants With HBV Ribonucleic Acid (RNA) <LLOQ
timeFrame: Week 48
measure: Change From Baseline in Mean log10 HBV RNA On-Treatment
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 56.
measure: Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) On-Treatment
timeFrame: Baseline and Week 48
measure: Number of Participants With HBsAg Seroconversion
timeFrame: Week 48
measure: Number of Participants With Normal Alanine Aminotransferase (ALT)
timeFrame: Baseline and at pre-specified time points up to 96 weeks
measure: Plasma Levels of VBR
timeFrame: Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks, and at Week 52
measure: Plasma Levels of AB-729
timeFrame: 2 hours after dosing at pre-specified time points up to 40 weeks
measure: Plasma Levels of SOC NrtI (ETV, TDF, TAF)
timeFrame: Before dosing at Baseline (Day 1) and at pre-specified time points up to 48 weeks
measure: Change From Baseline in Mean log10 Serum Hepatitis B Surface Antigen (HBsAg) Off-Treatment
timeFrame: Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
measure: Change From Baseline in Mean log10 HBV RNA Off-Treatment
timeFrame: Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
measure: Change From Baseline in Mean log10 Hepatitis B Core-related Antigen (HBcrAg) Off-Treatment
timeFrame: Weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92 and 96.
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Saint Vincent's Hospital Sydney
state: New South Wales
city: Kogarah
country: Australia
facility: Saint George Hospital - Australia
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Footscray
country: Australia
facility: Footscray Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Melbourne Health
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center Aleksandrovska
state: Sofia City
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda Hospital
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment St. Ivan Rilski
city: Stara Zagora
country: Bulgaria
facility: Nov Rehabilitatsionen Tsentar EOOD
city: Vancouver
country: Canada
facility: Vancouver Infectious Disease Centre
state: British Columbia
city: Vancouver
country: Canada
facility: Pacific Gastroenterology Associates
state: British Columbia
city: London
country: Canada
facility: University Hospital - London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Québec
country: Canada
facility: Centre Hospitalier Université de Québec - Université Laval
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital
Study officials:
References:
citation: 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.