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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Randomized, Open Label Study to Evaluate the Efficacy and Safety of Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF)-Containing Regimens in Subjects With Chronic HBV Infection and Stage 2 or Greater Chronic Kidney Disease Who Have Received a Liver Transplant

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: TAF
* Drug: TDF
* Drug: Other approved antivirals


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAF<br>TAF 25 mg once daily for 48 weeks | Drug: TAF<br>* Tablet administered orally<br>* Other names: Vemlidy®;|
| Active Comparator: TDF-Containing Regimens<br>TDF alone or in combination with other approved antivirals per local practice for 48 weeks | Drug: TDF<br>* Tablet administered orally<br>Drug: Other approved antivirals<br>* Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice<br>|
| Experimental: Optional Treatment Extension Phase<br>After Week 48, participants will be eligible to receive TAF 25 mg once daily for an additional 144 weeks. | Drug: TAF<br>* Tablet administered orally<br>* Other names: Vemlidy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) at Week 24 Using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation |  | Baseline, Week 24 | 
| Percentage of Participants With HBV DNA < 20 IU/mL at Week 24 |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 |  | Baseline, Week 24 | 
| Percent Change From Baseline in Hip BMD at Week 48 |  | Baseline, Week 48 | 
| Percent Change From Baseline in Spine BMD at Week 24 |  | Baseline, Week 24 | 
| Percent Change From Baseline in Spine BMD at Week 48 |  | Baseline, Week 48 | 
| Change From Baseline in Serum Creatinine at Week 24 |  | Baseline, Week 24 | 
| Change From Baseline in Serum Creatinine at Week 48 |  | Baseline, Week 48 | 
| Change From Baseline in Serum eGFR_CKD-EPI at Week 48 |  | Baseline, Week 48 | 
| Percentage of Participants With HBV DNA < 20 IU/mL at Week 48 |  | Week 48 |