None listed
Conditions
Brief 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).
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 combinat
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.
Sponsors
Gilead Sciences, Inc.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
Outcome results
None listed