Efficacy and Safety of Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF)-Containing Regimens in Participants With Chronic Hepatitis B Virus (HBV) Infection and Stage 2 or Greater Chronic Kidney Disease Who Have Received a Liver Transplant
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Kidney Diseases; Renal Insufficiency, Chronic
Intervention: TAF; TDF; Other approved antivirals
Intervention description: Tablet administered orally; Tablet administered orally; Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice
Intervention MeSH terms: Antiviral Agents
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objectives of this study are to evaluate the safety, tolerability, and efficacy
      of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF)-containing regimens
      at Week 24 in participants with chronic hepatitis B virus (HBV) infection and Stage 2 or
      greater chronic kidney disease who have received a liver transplant.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Must have the ability to understand and sign a written informed consent form; consent
             must be obtained prior to initiation of study procedures

          -  Documented evidence of chronic HBV infection prior to transplantation

          -  Primary or secondary (re-transplant), liver alone or liver and kidney transplant
             recipient from deceased or living donor

          -  Liver Transplant ≥ 12 weeks prior to screening

          -  Maintained on TDF alone or in combination with other approved antivirals for HBV
             prophylaxis or treatment

          -  Have been on approved HBV oral antiviral (OAV) treatment for at least 12 weeks
             post-transplant prior to screening, with HBV DNA < lower limit of quantification
             (LLOQ) at screening

          -  Screening estimated glomerular filtration rate using the chronic kidney disease
             epidemiology collaboration (eGFR_CKD-EPI) < 90 ml/min/1.73m^2

          -  Male participants and female participants of childbearing potential who engage in
             heterosexual intercourse must agree to use protocol specified method(s) of
             contraception

          -  Women considered of child bearing potential must have a negative serum pregnancy test
             at Screening and a negative urine test at Baseline before dosing

          -  Must be willing and able to comply with all study requirements

        Key Exclusion Criteria:

          -  Multi-organ transplant that includes heart or lung recipient (participants who have
             their liver transplant as part of a liver-kidney dual transplant are eligible to
             enroll)

          -  Participants with history of de novo or recurrent hepatocellular carcinoma (HCC)
             post-transplant and at screening

          -  Histological evidence of unresolved transplant rejection

          -  Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy,
             hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated
             cirrhosis

          -  Participants meeting any of the following laboratory parameters at screening:

               -  Alanine aminotransferase (ALT) > 10 × the upper limit of normal (ULN)

               -  International normalized ratio (INR) > 1.5 × ULN unless the participant is stable
                  on anticoagulant regimen affecting INR

               -  Albumin < 3.0 g/dL

               -  Direct bilirubin ≥ 4 × ULN

               -  Platelet count < 50,000/mL

          -  Co-infection with HIV or hepatitis C virus (HCV)

          -  Recent (within 4 weeks of Screening) episode or infection requiring systemic
             antibiotics

          -  Use of any prohibited medications listed within 28 days of the Baseline/Day 1 visit

          -  Malignancy within 5 years prior to screening, with the exception of specific cancers
             that are cured by surgical resection (e.g., basal cell skin cancer, etc.) or
             hepatocellular carcinoma. Participants under evaluation for possible malignancy are
             not eligible

          -  Significant cardiovascular, pulmonary, or neurological disease

          -  Use of investigational agents within 3 months of screening, unless allowed by the
             Sponsor

          -  Use of any prohibited medications

          -  Current alcohol or substance abuse judged by the investigator to potentially interfere
             with participant compliance

          -  Known hypersensitivity to study drugs, metabolites or formulation excipients

          -  Lactating females or those who may wish to become pregnant during the course of the
             study

        NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.