ActivePhase 2ACTRN12616000898459

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 Hepatitis B (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

Sponsor

Gilead Sciences, Inc.

Enrollment

50 participants

Start Date

Sep 15, 2016

Study Type

Interventional

Conditions

Chronic Kidney Disease Chronic Hepatitis B

Summary

This is a randomized, open-label, single center Phase 2 study to evaluate the safety and efficacy of TAF 25 mg daily versus TDF in adult chronic hepatitis B infection (CHB) subjects with Stage 2 or greater chronic kidney disease and have received a liver transplant. Approximately 60 subjects will be randomized in a 1:1 ratio to either continue current treatment regimen with TDF alone or in combination with other approved antivirals or to receive TAF 25 mg oral daily. At least 50 subjects will be enrolled with renal function < 50 ml/min/1.73m^2. - Treatment Arm A: approximately 30 subjects administered TAF 25 mg oral daily - Treatment Arm B: approximately 30 subjects to continue administration of TDF alone or in combination with other approved antivirals as per local practice. After Week 48, all subjects will be eligible to continue in the optional treatment extension phase, wherein they will receive TAF 25 mg daily and will be followed for an additional 96 weeks. The primary analysis will occur at Week 24 with the primary efficacy endpoint being the maintenance of viral suppression (HBV DNA < 20 IU/mL).

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria13

Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
Adult male or non-pregnant female subjects, over 18 years of age based on the date of the screening visit
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 OAV treatment for at least 12 weeks post-transplant prior to screening, with HBV DNA < LLOQ at screening
Screening renal function < 90 ml/min/1.73m^2
Male subjects and female subjects 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 Criteria20

Multi-organ transplant that includes heart or lung recipient (subjects who have their liver transplant as part of a liver-kidney dual transplant are eligible to enroll)
Subjects 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
Subjects meeting any of the following laboratory parameters at screening:
a) ALT > 10× the upper limit of normal (ULN)
b) INR > 1.5 × ULN unless the subject is stable on anticoagulant regimen affecting INR
c) Albumin < 3.0 g/dL
d) Direct bilirubin => 4 × ULN
e) Platelet count < 50,000/mL
Co-infection with HIV or HCV
Recent (within 4 weeks of Screening) episode or infection requiring systemic antibiotics
Use or planned use of T-cell depleting/masking antibodies, systemic antineoplastic agents, cyclosporine > 300 mg/day, or use of any prohibited medications 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. Subjects 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 concomitant medications
Current alcohol or substance abuse judged by the investigator to potentially interfere with subject 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

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Interventions

Approximately 60 subjects with chronic hepatitis B and Stage 2 or greater chronic kidney disease and have received a liver transplant will be assigned to one of the two treatment arms (A:B) for 48 weeks. Randomization will be stratified by baseline renal function. - Treatment Arm A: approximately 30 subjects administered Tenofovir Alafenamide (TAF) 25 mg oral daily - Treatment Arm B: approximately 30 subjects to continue administration of Tenofovir Disoproxil Fumarate (TDF) alone or in combination with other approved antivirals per local practice; After Week 48, during the optional treatment extension phase, subjects in treatment arms A and B will be eligible to receive TAF 25 mg daily and will be followed for an additional 96 weeks. An accountability check at each visit, Drug tablet return and lab tests are all part of the protocol to manage and monitor adherence.