Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Positive for Hepatitis B e Antigen
- Conditions
- HBeAg-positive Chronic Hepatitis B
- Interventions
- Drug: TAFDrug: TDFDrug: TDF PlaceboDrug: TAF Placebo
- Registration Number
- NCT01940471
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection.
- Detailed Description
This study GS-US-320-0110 is a multi-center clinical trial planned to enroll participants in multiple countries, including China. However, due to the review timeline difference in China, full enrollment was reached in the main study before China was able to participate. Therefore, details for the China cohort are registered separately (NCT02836249) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 875
-
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.
-
Documented evidence of chronic HBV infection.
-
HBeAg-positive, chronic hepatitis B with all of the following:
- HBeAg-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 electrocardiogram (ECG).
Key
- 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 virus, human immunodeficiency virus (HIV), or hepatitis D virus.
- Evidence of hepatocellular carcinoma .
- Any history of, or current evidence of, clinical 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; individuals 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.
- Individuals receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or individuals 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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TAF 25 mg TAF TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3). TAF 25 mg TDF Placebo TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3). TDF 300 mg TDF TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3). TDF 300 mg TAF Placebo TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3). Open-label TAF TAF All participants who complete the double-blind period (96 weeks or 144 weeks) will be eligible to receive open-label TAF until Week 384 of the study. After the end of study treatment, participants can either switch to commercially available anti-HBV treatments in their country or will be followed every 4 weeks, for up to 24 weeks off treatment (treatment-free follow-up (TFFU)) for safety assessment.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48 Week 48
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48 Week 48 Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 Baseline, Week 48 Change From Baseline at Week 48 in Serum Creatinine Baseline, Week 48 Percent Change From Baseline in Spine BMD at Week 48 Baseline, Week 48
Trial Locations
- Locations (158)
Gleneagles Global Hospital
🇮🇳Hyderabad, India
Gordon and Leslie Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
MHAT Alexandrovska Medical University, Sofia
🇧🇬Sofia, Bulgaria
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Tokuda Hospital - Sofia
🇧🇬Sofia, Bulgaria
MHAT Sofia Med
🇧🇬Sofia, Bulgaria
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Zeidler Ledcor Centre Division of Gastroenterology / Department of Medicine
🇨🇦Edmonton, Alberta, Canada
Liver and Intestinal Research Centre
🇨🇦Vancouver, British Columbia, Canada
Vancouver Infectious Disease Research and Care Centre
🇨🇦Vancouver, British Columbia, Canada
Hopital Pitie Salpetriere
🇫🇷Paris, France
University of Manitoba, Health Sciences Center
🇨🇦Winnipeg, Manitoba, Canada
Ankara Üniversitesi Gastroenteroloji Bilim Dalı Cebeci
🇹🇷Ankara, Turkey
Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika
🇵🇱Bialystok, Poland
Dicle University Medical Faculty Department of Infectious Diseases
🇹🇷Diyarbakir, Turkey
Istanbul Universitesi Cerrahpassa Tip Fakultesi Enfeksiyon
🇹🇷Istanbul, Turkey
Research Institute of Influenza
🇷🇺Saint-Petersburg, Russian Federation
Institute of Clinical Immunology RAMS, Clinic of Immunopathology
🇷🇺Novosibirsk, Russian Federation
Scientific Research Institute of Clinical Immunology
🇷🇺Novosibirsk, Russian Federation
Gastromedica SRL
🇷🇴Iasi, Romania
Changi General Hospital Pte Ltd.
🇸🇬Singapore, Singapore
Hualien Tzu Chi Medical Center
🇨🇳Hualien, Taiwan
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Ege Universitesi Tip Fakultesi Hastanesi
🇹🇷Izmir, Turkey
People's Friendship University of Russia
🇷🇺Moscow, Russian Federation
SPZOZ, Wojewódzki Specjalistyczny Szpital
🇵🇱Lodz, Poland
1st Moscow State Medical University University Clinical Hospital #3
🇷🇺Moscow, Russian Federation
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Policlinico Universitario G. Martino via Consolare
🇮🇹Messina, Italy
SP ZOZ Wojewódzki Szpital Zakazny
🇵🇱Warszawa, Poland
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Korea, Republic of
Royal Free Hospital
🇬🇧London, United Kingdom
Auckland Clinical Studies Limited
🇳🇿Auckland, New Zealand
Singapore General Hospital
🇸🇬Singapore, Singapore
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Yonsei Unversity Wonju
🇰🇷Wŏnju, Korea, Republic of
Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases
🇷🇺Lipetsk, Russian Federation
Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"
🇷🇴Bucharest, Romania
Spitatul Clinic de Boli Infectioase Constanta
🇷🇴Constanţa, Romania
Spitalul Clinic Judetean de Urgenta Timisoara
🇷🇴Timişoara, Romania
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Cathay General Hospital
🇨🇳Taipei, Taiwan
Waikato Hospital (District Health Board)
🇳🇿Hamilton, New Zealand
Kaohsiung Med. College Hosp. Dept. of Internal Medicine
🇨🇳Kaohsiung, Taiwan
Szpital Specjalistyczny
🇵🇱Chorzow, Poland
University of Uludag
🇹🇷Bursa, Turkey
National University Hospital Singapore
🇸🇬Singapore, Singapore
Chiayi Christian Hospital
🇨🇳Chiayi, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
King's College Hospital
🇬🇧London, United Kingdom
Far-Eastern Memorial Hospital
🇨🇳Taipei, Taiwan
University of Miami
🇺🇸Miami, Florida, United States
Coalition of Inclusive Medicine
🇺🇸Los Angeles, California, United States
Research and Education, Inc.
🇺🇸San Diego, California, United States
Tufts Medical Center, Inc
🇺🇸Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Jefferson Medical College
🇺🇸Philadelphia, Pennsylvania, United States
Xiaoli Ma, PC
🇺🇸Philadelphia, Pennsylvania, United States
Texas Clinical Research Institute, LLC
🇺🇸Arlington, Texas, United States
Kelsey Research Foundation
🇺🇸Houston, Texas, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
St. Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
Inspiration Research Limited
🇨🇦Toronto, Ontario, Canada
BYL Nair Hospital & T N Medical College
🇮🇳Mumbai, Maharashtra, India
SMS Medical College & Hospital
🇮🇳Jaipur, Rajasthan, India
Barts & The London NHS Trust
🇬🇧London, United Kingdom
Limited Liability Company "Modern Medicine Clinic"
🇷🇺Moscow, Russian Federation
Medical Company Hepatology
🇷🇺Samara, Russian Federation
Sverdlovsk Regional Clinical Hospital #1
🇷🇺Yekaterinburg, Russian Federation
Municipal Clinical Hospital n.a. S.P. Botkin
🇷🇺Saint-Petersburg, Russian Federation
Digestive Disease Associates, PA
🇺🇸Catonsville, Maryland, United States
Huntington Medical Research Institutes
🇺🇸Pasadena, California, United States
Silicon Valley Research Institute
🇺🇸San Jose, California, United States
Sing Chan Private Practice
🇺🇸Flushing, New York, United States
New Discovery, LLC
🇺🇸Flushing, New York, United States
Westmead Hospital Westmead
🇦🇺Westmead, New South Wales, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Footscray Hospital
🇦🇺Footscray, Victoria, Australia
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
MMA Hospital of Active Treatment
🇧🇬Sofia, Bulgaria
University of Calgary
🇨🇦Calgary, Alberta, Canada
Gastrointestinal Research Institute (GIRI)
🇨🇦Vancouver, British Columbia, Canada
University Health Network / Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Toronto Liver Centre
🇨🇦Toronto, Ontario, Canada
Hopital Beaujon
🇫🇷Clichy, France
Hopital Civil de Strasbourg
🇫🇷Strasbourg, France
Princess Margaret Hospital
🇭🇰Lai Chi Kok, Hong Kong
Hopital Paul Brousse
🇫🇷Villejuif, France
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Government Medical College and Superspecialty Hospital
🇮🇳Nagpur, Maharashtra, India
Postgraduate Institute of Medical Education & Research
🇮🇳Kolkata, India
YR Gaitonde Centre for AIDS Research and Education
🇮🇳Chennai, India
Midas Multispecialty Hospital
🇮🇳Nagpur, Maharashtra, India
VGM Hospital
🇮🇳Coimbatore, India
S. R Kalla Memorial Gastro & General Hospital
🇮🇳Jaipur, India
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals
🇮🇳Hyderabad, India
Peerless Hospital & B.K.Roy Research Center
🇮🇳Kolkata, India
Seth GS Medical College and KEM Hospital
🇮🇳Mumbai, India
All India Institute of Medical Sciences
🇮🇳New Delhi, India
Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
🇮🇹Bologna, Italy
Istituto Europeo di Oncologia
🇮🇹Bologna, Italy
Global Hospital Super Specialty & Transplant Centre
🇮🇳Parel, India
Nirmal Hospital
🇮🇳Surat, India
Azienda Ospedaliero Universitaria Ospedali Riuniti di
🇮🇹Foggia, Italy
Azienda Ospedale San Paolo
🇮🇹Milano, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Kyushu University Hospital
🇯🇵Fukuoka, Fukuoka-shi, Japan
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Shin-Kokura Hospital
🇯🇵Fukuoka, Japan
Kagawa Prefectural Central Hospital
🇯🇵Kagawa, Japan
Yamanashi Prefectural Central Hospital
🇯🇵Kofu, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Japan
Kurume University Hospital
🇯🇵Kurume, Japan
Hyogo College of Medicine
🇯🇵Nishinomiya, Japan
Japan Red Cross Musashino Hospital
🇯🇵Musashino, Japan
Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Osaka Red Cross Hospital
🇯🇵Osaka, Japan
National Hospital Organization Nagasaki Medical Center
🇯🇵Omura, Japan
Medical Hospital of Tokyo Medical and Dental University
🇯🇵Tokyo, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Kosin University College of Medicine
🇰🇷Busan, Seo-gu, Korea, Republic of
Hokkaido University Hospital
🇯🇵Sapporo, Japan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
SoonChunHyang University Hospital Cheonan
🇰🇷Cheonan, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Konyang University Hospital
🇰🇷Daejeon, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Inje University Ilsan Paik Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Ajou University Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-Do, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Seoul Saint Mary Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Chung-Ang University Hospital
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Centrum Badan Klinicznych
🇵🇱Wroclaw, Poland
Scientific Research Institute of Nutrition
🇷🇺Moscow, Russian Federation
Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
🇷🇴Bucuresti, Romania
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
National Hospital Organization Kyushu Medical Center
🇯🇵Fukuoka, Japan
Sir Ganga Ram Hospital
🇮🇳New Delhi, India
Dr. John Farley, Inc.
🇨🇦Vancouver, British Columbia, Canada
Institute of Liver and Biliary Sciences
🇮🇳New Delhi, India
Prince of Wales Hospital
🇭🇰Sha Tin, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
🇭🇰Tai Po, Hong Kong
Tuen Mun Hospital
🇭🇰Tuen Mun, Hong Kong