CTRI/2014/01/004329 [Registered on: 20/01/2014] Trial Registered Prospectively
Last Modified On:
12/01/2021
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
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-Positive, Chronic Hepatitis B
Scientific Title of Study
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-Positive, Chronic Hepatitis B
Klinera Corporation India, 401, Hill View Industrial Estate LBS Marg, Ghatkopar West Mumbai MAHARASHTRA 400086 India
Phone
2225091470
Fax
02225004588
Email
sunil.verma@klinera.com
Source of Monetary or Material Support
Gilead Sciences, Inc.
Primary Sponsor
Name
Gilead Sciences Inc
Address
Gilead Sciences, Inc. 333 Lakeside Drive Foster City, CA 94404 USA
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
KlinEra Corporation India
401, Hill View Industrial Estate
Ghatkopar West, Mumbai-400086
Countries of Recruitment
Australia Bulgaria Canada China Democratic People's Republic of Korea France Germany Hong Kong India Italy Japan New Zealand Poland Romania Russian Federation Singapore Spain Taiwan Turkey United Kingdom United States of America Viet Nam
Department of
Gastroenterology and
Human Nutrition, Room
number: 3105, 3rd
Floor, Teaching Block,
All India Institute of
Medical Sciences, Ansari Nagar, New Delhi, Delhi -110029 New Delhi DELHI
Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospitals
Department of Hepatology, Institute of Liver Diseases, HPB Surgery and Transplant, Global Hospitals Dr. E. Borges Road, Hospital Avenue, Opp. Shirodkar High School, Parel, Mumbai- 400012, Maharashtra, India Mumbai MAHARASHTRA
Peerless Hospital & BK Roy Medical Research Center
Department of Gastroenterology,
Peerless Hospital & BK Roy Medical Research Center,
Mail 360, Panchasayar
Kolkata 700094
West Bengal INDIA
Kolkata WEST BENGAL
Chronic hepatitis B virus (HBV) HBeAg-positive infection ,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Drug: Placebo to match tenofovir alafenamide
Placebo to match tenofovir alafenamide administered as a tablet orally once daily
Drug: Placebo to match tenofovir DF
Placebo to match tenofovir DF administered as a tablet orally once daily
Treatment Arm B: 288 subjects TDF 300 mg QD and matched
placebo of TAF 25 mg QD
Total duration of therapy per trial subject is 144 weeks.
Intervention
Drug: Tenofovir alafenamide
Tenofovir alafenamide 25 mg tablet administered orally once daily
Drug: Tenofovir disoproxil fumarate
Tenofovir disoproxil fumarate 300 mg tablet administered orally once daily
Other Name: Viread®
Approximately 864 subjects will be randomized in a
2:1 ratio (A:B) to the treatment arms and will be stratified by
plasma HBV DNA level (≥ 8 log10 IU/mL vs. 8 log10 IU/mL) and oral antiviral treatment status (treatment-naïve vs.
treatment-experienced).
Treatment Arm A: 576 subjects TAF 25 mg QD and matched placebo of TDF 300 mg QD
Total duration of therapy per trial subject is 144 weeks.
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
ExclusionCriteria
Details
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
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
The proportion of participants with hepatitis B e antigen HBeAg loss with seroconversion to antibody
against HBeAb anti HBe at Week 48.
Percent change from baseline at Week 48 in hip and spine bone mineral density BMD
Change from baseline at Week 48 in serum creatinine
The proportion of subjects with ALT normalization (by central laboratory and AASLD criteria)at Weeks 48, 96, 144, and 240, and 384
The proportion of subjects with HBsAg & HBeAg loss at Weeks 48, 96, 144, 240, and 384.
Week 24, 48, 72, 96, 120, and 144, and every 48 weeks until Week 384/ED.
Target Sample Size
Total Sample Size="864" Sample Size from India="410" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
The purpose of this study is to compare the efficacy of tenofovir
alafenamide (TAF) 25 mg QD versus tenofovir disoproxil fumarate (TDF) 300
mg QD for the treatment of HBeAg-positive, chronic B at Week 48 in
treatment naïve and treatment-experienced subjects. The primary efficacy
parameter is the proportion of subjects with plasma HBV DNA levels below 29
IU/mL. To compare the safety and tolerability of TAF 25 mg QD versus TDF 300 mg
QD for the treatment of HBeAg-positive, chronic hepatitis B at Week 48 in
treatment-naïve and treatment-experienced subjects. To compare the safety of
TAF 25 mg QD versus TDF 300 mg QD as determined by the percent change from
baseline in hip and spine BMD and in serum creatinine at Week 48.After
144 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 an
additional 240 weeks (Week 144 through Week 384/ED). Subjects already
assigned to open-label TAF 25 mg QD at Week 96 per Amendment 1 or 2 will
continue on open-label TAF 25 mg QD until Week 384/ED. All subjects who
complete the double-blind period of treatment are eligible for participation in
the open-label TAF 25 mg QD extension period. Subjects who permanently
discontinue study drug(either prematurely [ED] or at the end of study [Week
384]) for reasons other than HBsAg loss with confirmed seroconversion to
anti-HBs, will be followed every 4 weeks for 24 weeks off treatment or until
initiation of alternative, commercially available HBV therapy, whichever occurs
first.