Double-Blind Study to Evaluate theSafety and Efficacy of Tenofovir Alafenamide (TAF) 25 mgQD versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QDfor the Treatment of HBeAg-Positive, Chronic Hepatitis B
- Conditions
- Chronic hepatitis B virus (HBV) HBeAg-positive infection
- Registration Number
- CTRI/2014/01/004329
- Lead Sponsor
- Gilead Sciences Inc
- Brief Summary
The purpose of this study is to compare the efficacy of tenofoviralafenamide (TAF) 25 mg QD versus tenofovir disoproxil fumarate (TDF) 300mg QD for the treatment of HBeAg-positive, chronic B at Week 48 intreatment naïve and treatment-experienced subjects. The primary efficacyparameter is the proportion of subjects with plasma HBV DNA levels below 29IU/mL. To compare the safety and tolerability of TAF 25 mg QD versus TDF 300 mgQD for the treatment of HBeAg-positive, chronic hepatitis B at Week 48 intreatment-naïve and treatment-experienced subjects. To compare the safety ofTAF 25 mg QD versus TDF 300 mg QD as determined by the percent change frombaseline in hip and spine BMD and in serum creatinine at Week 48.After144 weeks of blinded randomized treatment (96 weeks under Amendment 1 or 2),each subject will switch to open-label TAF 25 mg QD for up to anadditional 240 weeks (Week 144 through Week 384/ED). Subjects alreadyassigned to open-label TAF 25 mg QD at Week 96 per Amendment 1 or 2 willcontinue on open-label TAF 25 mg QD until Week 384/ED. All subjects whocomplete the double-blind period of treatment are eligible for participation inthe open-label TAF 25 mg QD extension period. Subjects who permanentlydiscontinue study drug(either prematurely [ED] or at the end of study [Week384]) for reasons other than HBsAg loss with confirmed seroconversion toanti-HBs, will be followed every 4 weeks for 24 weeks off treatment or untilinitiation of alternative, commercially available HBV therapy, whichever occursfirst.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 864
1 Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2 Adult males and non pregnant, non lactating females, 18 years of age and older 3 Documented evidence of chronic HBV Chronic Hepatitis B infection 4 HBeAg positive, chronic hepatitis B with all of the following 1 HBeAg positive at screening 2 Screening HBV DNA more than or equal to 2 x 10 raise to 4 IU per mL 3 Screening serum alanine aminotransferase ALT level more than 60 U per L for males or more 38 U per L for females and less than or equal to 10 x the upper limit of the normal range ULN 5 Treatment naive participants defined as less than 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue OR treatment experienced participants defined as participants meeting all entry criteria i.e. including HBV DNA and serum ALT criteria and with more than or equal 12 weeks of previous treatment with any nucleoside or nucleotide analogue 6 Previous treatment with interferon pegylated or non pegylated must have ended at least 6 months prior to the baseline visit 7 Adequate renal function 8 Normal ECG.
- 1 Females who are breastfeeding 2 Males and females of reproductive potential who are unwilling to use an effective, protocol specified methods of contraception during the study 3 Co infection with hepatitis C, HIV or hepatitis D 4 Evidence of hepatocellular carcinoma 5 Any clinical and or laboratory evidence of hepatic decompensation 6 Abnormal hematological and biochemical parameters, including aspartate aminotransferase AST more than 10 x ULN 7 Received solid organ or bone marrow transplant 8 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 9 Currently receiving therapy with immunomodulators eg.
- corticosteroids, investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion 10 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 11 Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance 12 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The proportion of participants with hepatitis B virus HBV DNA less than 29 IU per mL .The primary efficacy endpoint is determined by the achievement of HBV DNA less than 29 IU per mL at Week 48.The proportion of subjects with plasma HBV DNA 29 IU/mL at Weeks 96,144, and 240,and 384.The proportion of subjects with HBsAg seroconversion to anti-HBs at Weeks 48, 96, 144,240, and 384 Week 48 | Week 96 | Week 120 | Week 144 | Week 240 | Week 384
- Secondary Outcome Measures
Name Time Method The proportion of participants with hepatitis B e antigen HBeAg loss with seroconversion to antibody against HBeAb anti HBe at Week 48.
Trial Locations
- Locations (18)
All India Institute of Medical Sciences
🇮🇳Delhi, DELHI, India
Centre for Liver Research & Diagnostics ,Deccan College of Medical Sciences and Allied Hospitals
🇮🇳Hyderabad, ANDHRA PRADESH, India
Department of Hepatology, Postgraduate Institute of Medical Education and Research
🇮🇳Chandigarh, CHANDIGARH, India
Dr.Pravin Rathi
🇮🇳Mumbai, MAHARASHTRA, India
Global Hospitals
🇮🇳Hyderabad, ANDHRA PRADESH, India
Govt. Medical College & Super Speciality Hospital
🇮🇳Nagpur, MAHARASHTRA, India
Institute of Liver and Biliary Sciences
🇮🇳Delhi, DELHI, India
Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospitals
🇮🇳Mumbai, MAHARASHTRA, India
Institute of Post Graduate Medical Education And Research
🇮🇳Kolkata, WEST BENGAL, India
Midas Multispeciality Hospital
🇮🇳Nagpur, MAHARASHTRA, India
Scroll for more (8 remaining)All India Institute of Medical Sciences🇮🇳Delhi, DELHI, IndiaDr ShalimarPrincipal investigator11-26596643drshalimar@yahoo.com