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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: TAF; Drug: TDF; Drug: Other approved antivirals

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2016
• Primary Completion (Actual): February 8, 2018
• Study Completion (Actual): May 5, 2021

Study Registration Dates

• First Submitted: August 8, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): June 8, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Urologic Diseases; Liver Diseases; Renal Insufficiency; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Kidney Diseases; Renal Insufficiency, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents
• Other Study ID Numbers: GS-US-320-3912; ACTRN12616000898459 (Registry Identifier: ANZCTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes