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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02862548
• Other study ID #: GS-US-320-3912
• Secondary ID: ACTRN12616000898
• Status: Completed
• Phase: Phase 2
• Start date: September 16, 2016
• Est. completion date: May 5, 2021

Study information

• Verified date: June 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: May 5, 2021
• Est. primary completion date: February 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• TAF
Tablet administered orally
• TDF
Tablet administered orally
• Other approved antivirals
Other approved antivirals (such as lamivudine, entecavir, or immunoglobulin antihepatitis B) administered per local practice

Locations

Country	Name	City	State
New Zealand	Auckland City Hospital	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of Participants With HBV DNA < 20 IU/mL at Week 24		Week 24
Secondary	Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in Hip BMD at Week 48		Baseline, Week 48
Secondary	Percent Change From Baseline in Spine BMD at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in Spine BMD at Week 48		Baseline, Week 48
Secondary	Change From Baseline in Serum Creatinine at Week 24		Baseline, Week 24
Secondary	Change From Baseline in Serum Creatinine at Week 48		Baseline, Week 48
Secondary	Change From Baseline in Serum eGFR_CKD-EPI at Week 48		Baseline, Week 48
Secondary	Percentage of Participants With HBV DNA < 20 IU/mL at Week 48		Week 48