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

NCT ID: NCT02862548

Last Updated: 2022-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-16
• Study Completion Date: 2021-05-05

Brief 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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TAF

TAF 25 mg once daily for 48 weeks

Group Type: EXPERIMENTAL

TAF

Intervention Type: DRUG

Tablet administered orally

TDF-Containing Regimens

TDF alone or in combination with other approved antivirals per local practice for 48 weeks

Group Type: ACTIVE_COMPARATOR

TDF

Intervention Type: DRUG

Tablet administered orally

Other approved antivirals

Intervention Type: DRUG

Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice

Optional Treatment Extension Phase

After Week 48, participants will be eligible to receive TAF 25 mg once daily for an additional 144 weeks.

Group Type: EXPERIMENTAL

TAF

Intervention Type: DRUG

Tablet administered orally

Interventions

TAF

Tablet administered orally

Intervention Type: DRUG

TDF

Tablet administered orally

Intervention Type: DRUG

Other approved antivirals

Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice

Intervention Type: DRUG

Other Intervention Names

Vemlidy®

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Auckland City Hospital

Auckland, , New Zealand

Countries

New Zealand

Provided Documents

Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Study Protocol: Amendment 3

View Document

Document Type: Statistical Analysis Plan: Week 24 Analysis

View Document

Document Type: Statistical Analysis Plan: Final Analysis

View Document

Other Identifiers

ACTRN12616000898459

Identifier Type: REGISTRY

Identifier Source: secondary_id

GS-US-320-3912

Identifier Type: -

Identifier Source: org_study_id