A Phase 2, Randomized, Open Label Study to Evaluate the Efficacy and Safety of Tenofovir Alafenamide (TAF) versus Tenofovir Disoproxil Fumarate (TDF)–containing Regimens inSubjects with Chronic Hepatitis B (HBV) Infection and Stage 2 or Greater Chronic Kidney Disease Who Have Received a Liver Transplant

Phase 2

Active, not recruiting

• Conditions: Chronic Hepatitis B; Infection - Other infectious diseases; Renal and Urogenital - Kidney disease; Chronic Kidney Disease; Oral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

• Registration Number: ACTRN12616000898459
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-07-07
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1) Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
2) Adult male or non-pregnant female subjects, over 18 years of age based on the date of the screening visit
3) Documented evidence of chronic HBV infection prior to transplantation
4) Primary or secondary (re-transplant), liver alone or liver and kidney transplant recipient from deceased or living donor
5) Liver Transplant =>12 weeks prior to screening
6) Maintained on TDF alone or in combination with other approved antivirals for HBV
prophylaxis or treatment
7) Have been on approved HBV OAV treatment for at least 12 weeks post-transplant prior to screening, with HBV DNA < LLOQ at screening
8) Screening renal function < 90 ml/min/1.73m^2
9) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
10) Women considered of child bearing potential must have a negative serum
pregnancy test at Screening and a negative urine test at Baseline before dosing
11) Must be willing and able to comply with all study requirements

Exclusion Criteria

1) 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)
2) Subjects with history of de novo or recurrent hepatocellular carcinoma (HCC) post-transplant and at screening
3) Histological evidence of unresolved transplant rejection
4) Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, or other signs of decompensated cirrhosis
5) 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
6) Co-infection with HIV or HCV
7) Recent (within 4 weeks of Screening) episode or infection requiring systemic antibiotics
8) 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
9) 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
10) Significant cardiovascular, pulmonary, or neurological disease
11) Use of investigational agents within 3 months of screening, unless allowed by the Sponsor
12) Use of any prohibited concomitant medications
13) Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance
14) Known hypersensitivity to study drugs, metabolites or formulation excipients
15) Lactating females or those who may wish to become pregnant during the course of the study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change from baseline in renal function of TAF 25 mg daily versus TDF-containing regimens at Week 24. <br>eGFR is calculated by assessing Cystatin C and estimated serum creatinine clearance. [Assessment timepoints: <br>Creatinine Clearance: Baseline, Week 4, Week 8, Week 12, Week 20, and Week 24.<br>Cystatin C: Baseline, Week 4, Week 12, and Week 24.];Proportion of subjects with HBV DNA < 20 IU/mL at Week 24.<br>The subject's HBV DNA will be assessed using a plasma assay.<br>[Assessment timepoints: Baseline, Week 4, Week 8, Week 12, Week 20 and Week 24]