A Study Evaluating Treatment Regimens Containing Vebicorvir (ABI-H0731) in Participants With Chronic Hepatitis B Infection
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: VBR; AB-729; SOC NrtI
Intervention description: VBR is an HBV core protein inhibitor. Participants will receive VBR 300 mg tablets orally once daily (QD).; 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.; Participants will receive their SOC NrtI (ETV, TDF or TAF) tablet orally as per approved package insert.
Intervention MeSH terms: Tenofovir; Entecavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: cHBV; HBV; hepatitis B; vebicorvir; VBR; AB-729

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).
    

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.