Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Negative for Hepatitis B e Antigen
- Conditions
- HBeAg-negative Chronic Hepatitis B
- Interventions
- Drug: TAFDrug: TDFDrug: TDF PlaceboDrug: TAF Placebo
- Registration Number
- NCT01940341
- 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)-negative chronic hepatitis B virus (HBV) infection.
- Detailed Description
Study GS-US-320-0108 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 was registered separately (NCT02836236) on ClinicalTrials.gov as the China cohort will not be part of the main study analysis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 426
-
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.
-
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 Baseline.
-
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 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. TDF 300 mg TDF TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
- Primary Outcome Measures
Name Time Method Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL Week 48 The primary efficacy endpoint was determined by the achievement of HBV DNA \< 29 IU/mL at Week 48.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 Baseline, Week 48 Change From Baseline in Serum Creatinine at Week 48 Baseline, Week 48 Percent Change From Baseline in Spine BMD at Week 48 Baseline, Week 48
Trial Locations
- Locations (105)
University of Miami
🇺🇸Miami, Florida, United States
Spitatul Clinic de Boli Infectioase Constanta
🇷🇴Constanta, Romania
Barts and The London NHS Trust Royal London Hospital
🇬🇧London, United Kingdom
All India Institute of Medical Sciences
🇮🇳New Delhi, Delhi, India
Postgraduate Institute of Medical Education and Research
🇮🇳Chandigarh, India
Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
🇷🇴Bucharest, Bucuresti, Romania
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Global Hospitals
🇮🇳Hyderabad, Andhra Pradesh, India
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals
🇮🇳Hyderabad, Andhra Pradesh, India
SPZOZ, Wojewódzki Specjalistyczny Szpital
🇵🇱Lodz, Poland
IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Foggia, Italy
Clinical Infectious Hospital named after S.P.Botkin
🇷🇺Saint-Petersburg, Russian Federation
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
Japan Red Cross Musashino Hospital
🇯🇵Musashino, Japan
Osaka Red Cross Hospital
🇯🇵Osaka, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Japan
Medical Hospital of Tokyo Medical and Dental University
🇯🇵Tokyo, Japan
Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika
🇵🇱Bialystok, Poland
Infectious Clinical Hospital #1 of Moscow Healthcare Department
🇷🇺Moscow, Russian Federation
Research Institute of Influenza
🇷🇺Saint-Petersburg, Russian Federation
Research and Education, Inc.
🇺🇸San Diego, California, United States
Azienda Ospedaliero Universitaria Ospedali
🇮🇹Foggia, Italy
New Discovery, LLC
🇺🇸Flushing, New York, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
St. Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Sing Chan Private Practice
🇺🇸Flushing, New York, United States
Zeidler Ledcor Centre Division of Gastroenterology
🇨🇦Edmonton, Alberta, Canada
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Xiaoli Ma, PC
🇺🇸Philadelphia, Pennsylvania, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Gordon and Leslie Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
Hôpital de la Croix Rousse
🇫🇷Lyon cedex 04, France
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Hunter Holmes McGuire VA DVMC
🇺🇸Richmond, Virginia, United States
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Seth GS Medical College and KEM Hospital
🇮🇳Mumbai, Maharastra, India
Global Hospital Super Specialty & Transplant Centre
🇮🇳Parel, Mumbai, India
Hopital Civil de Strasbourg- CHU Service
🇫🇷Strasbourg, France
S. R Kalla Memorial Gastro & General Hospital
🇮🇳Jaipur, Rajasthan, India
Liver and Intestinal Research Centre
🇨🇦Vancouver, British Columbia, Canada
Gastrointestinal Research Institute (GIRI)
🇨🇦Vancouver, British Columbia, Canada
Nirmal Hospital
🇮🇳Surat, Gujarat, India
Dr. John Farley Inc.
🇨🇦Vancouver, British Columbia, Canada
Vancouver Infectious Disease Research and Care Centre
🇨🇦Vancouver, British Columbia, Canada
ID Care
🇺🇸Hillsborough, New Jersey, United States
Inspiration Research Limited
🇨🇦Toronto, Ontario, Canada
Kurume University Hospital
🇯🇵Kurume-shi, Fukuoka-ken, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Japan
Azienda Ospedaliera S. Orsola - Malpighi
🇮🇹Bologna, Italy
Kyushu University Hospital Fukuoka
🇯🇵Fukuoka, Fukuoka-shi, Japan
National Hospital Organization Nagasaki Medical Center
🇯🇵Omura-shi, Nagasaki, Japan
Novosibirsk State Medical University
🇷🇺Novosibirsk, Russian Federation
State Novosibirsk Regional Clinical Hospital
🇷🇺Novosibirsk, Russian Federation
Scientific Research Institute of Clinical Immunology
🇷🇺Novosibirsk, Russian Federation
1st Moscow State Medical University University Clinical Hospital #3
🇷🇺Moscow, Russian Federation
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Ankara Üniversitesi Gastroenteroloji Bilim Dalı Cebeci
🇹🇷Ankara, Turkey
Toronto Liver Centre
🇨🇦Toronto, Ontario, Canada
Asian Pacific Liver Center
🇺🇸Los Angeles, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
University California San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Silicon Valley Research Institute
🇺🇸San Jose, California, United States
Huntington Medical Research Institutes
🇺🇸Pasadena, California, United States
Digestive Disease Associates, PA
🇺🇸Catonsville, Maryland, United States
Institute of Post Graduate Medical Education And Research
🇮🇳Kolkata, West Bengal, India
Azienda Ospedaliero- Universitaria Pisana
🇮🇹Pisa, Italy
Shin-Kokura Hospital
🇯🇵Kitakyushu, Japan
The Hospital of Hyogo College of Medicine
🇯🇵Nishinomiya, Japan
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Gyeongsangnam-do, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Yonsei University, Severance Hospital
🇰🇷Seoul, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Auckland Clinical Studies Limited
🇳🇿Auckland, New Zealand
Szpital Specjalistyczny w Chorzowie Oddział
🇵🇱Chorzow, Poland
Centrum Badan Klinicznych - Przychodnia Badan
🇵🇱Wroclaw, Poland
Institutul National de Boli Infectioase Prof.Dr. Matei Bals
🇷🇴Bucuresti, Romania
Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"
🇷🇴Bucuresti, Romania
Gastromedica SRL
🇷🇴Iasi, Romania
Infection Center LLC Building 20, MSH #163 Territory Koltsovo
🇷🇺Koltsovo, Novosibirsk, Russian Federation
Limited Liability Company "Modern Medicine Clinic"
🇷🇺Moscow, Russian Federation
Kirov Medical Military Academy
🇷🇺Saint-Petersburg, Russian Federation
Hualien Tzu Chi Hospital
🇨🇳Hualien City, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Dicle University Medical Faculty Department of Infectious Diseases
🇹🇷Diyarbakir, Diyarbakri, Turkey
Ege Universitesi Tip Fakultesi Hastanesi
🇹🇷Izmir, Turkey
Istanbul Universitesi Cerrahpassa Tip Fakultesi Hastanesi
🇹🇷Istanbul, Turkey
Uludag Üniversitesi Tıp Fakültesi Gastroenteroloji
🇹🇷Bursa, Turkey
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, Nottinghamshire, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul Saint Mary Hospital
🇰🇷Seoul, Korea, Republic of
Chung-Ang University Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Institute of Liver and Biliary Sciences
🇮🇳New Delhi, India
Princess Margaret Hospital
🇭🇰Kwai Chung, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong SAR, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
🇭🇰Tai Po, Hong Kong
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong