A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B
This study has been completed.
The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA < 29 IU/mL at Week 48.
Primary Outcome Measures
The proportion of participants with hepatitis B virus (HBV) DNA < 29 IU/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
The primary efficacy endpoint is determined by the achievement of HBV DNA < 29 IU/mL at Week 48. Secondary Outcome Measures Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ] Change from baseline in serum creatinine at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ] Inclusion Criteria Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures Adult males and non-pregnant, non-lactating females, 18 years of age and older Documented evidence of chronic HBV (CHB) infection Hepatitis e antigen (HBeAg)-negative, chronic hepatitis B with all of the following: HBeAg-negative and hepatitis B e antibody (HBeAb) positive at screening Screening HBV DNA ≥ 2 x 10^4 IU/mL Screening serum alanine aminotransferase (ALT) level > 60 U/L (males) or > 38 U/L (females) and ≤ 10 x the upper limit of the normal range (ULN)
Treatment-naive participants (defined as < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue), OR treatment-experienced participants (defined as participants meeting all entry criteria [including HBV DNA and serum ALT criteria] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue) Previous treatment with interferon (pegylated or non pegylated) must have ended at least 6 months prior to the baseline visit. Adequate renal function Normal ECG Exclusion Criteria Females who are breastfeeding Males and females of reproductive potential who are unwilling to use an “effective”, protocol-specified method(s) of contraception during the study Co-infection with hepatitis C, HIV, or hepatitis D Evidence of hepatocellular carcinoma Any clinical and/or laboratory evidence of hepatic decompensation Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) > 10 x ULN
Received solid organ or bone marrow transplant
History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; participants under evaluation for possible malignancy are not eligible
Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion
Subjects receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or subjects with a known hypersensitivity to study drugs, metabolites, or formulation excipients
Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance
Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements