A Study Evaluating Treatment Intensification With ABI-H0731 in Participants With Chronic Hepatitis B Infection on Nucleos(t)Ide Reverse Transcriptase Inhibitors
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: ABI-H0731; Placebo; NrtI
Intervention description: Participants will receive ABI-H0731 tablets orally once daily; Participants will receive placebo to ABI-H0731 tablets orally once daily; Entecavir (ETV), tenofovir alafenamide (TAF), or tenofovir disoproxil fumarate (TDF) SOC according to the respective package insert
Intervention MeSH terms: Reverse Transcriptase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study will explore the safety and antiviral activity of ABI-H0731 when added to a
      nucleos(t)ide reverse transcriptase inhibitor (NrtI) in participants who are partially
      virologically suppressed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body mass index (BMI) 18 to 36 kg/m^2 and a minimum body weight of 45 kg (inclusive)

          -  In good general health except for chronic hepatitis B (CHB)

          -  HBeAg positive or HBeAg negative chronic hepatitis B

          -  HBV DNA >LLOQ using a commercially available assay with LLOQ=20 IU/mL

          -  On a stable NrtI regimen (ETV, TDF or TAF) for more than 12 months

          -  Lack of cirrhosis or advanced liver disease

        Exclusion Criteria:

          -  Current or prior treatment for CHB with lamivudine, telbivudine, adefovir, HBV core
             inhibitor, or previous treatment with an investigational agent for HBV infection

          -  Presence of substitutions in the HBV polymerase coding region which may confer reduced
             susceptibility to NrtIs

          -  Co-infection with human immunodeficiency virus, hepatitis A virus, hepatitis C virus,
             hepatitis E virus, or hepatitis D virus

          -  Females who are lactating or wish to become pregnant during the course of the trial

          -  History or evidence of advanced liver disease or hepatic decompensation

          -  Clinically significant cardiac disease including poorly-controlled or unstable
             hypertension; pulmonary disease; chronic or recurrent renal or urinary tract disease;
             liver disease other than CHB; 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 trial participation

          -  History of hepatocellular carcinoma (HCC)

          -  Exclusionary laboratory parameters at Screening:

               -  Platelet count <100,000/mm^3

               -  Albumin <lower limit of normal

               -  Total bilirubin >1.2 × upper limit of normal (ULN)

               -  Direct bilirubin >1.2 × ULN

               -  ALT >10 × ULN

               -  Serum alpha fetoprotein (AFP) ≥100 ng/mL. If AFP at Screening is >ULN but <100
                  ng/mL, the participant is eligible if a hepatic imaging trial prior to initiation
                  of study drug reveals no lesions indicative of possible HCC.

               -  International Normalized Ratio >1.5 × ULN

               -  Glomerular filtration rate <50 mL/min/1.73 m^2 by Chronic Kidney Disease
                  Epidemiology Collaboration equation

               -  Any other laboratory abnormality deemed clinically significant by the Sponsor or
                  the Investigator.