Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Positive Hepatitis B

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01940471
First received: August 20, 2013
Last updated: April 25, 2016
Last verified: April 2016
  Purpose
This study will compare the safety and efficacy of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with chronic hepatitis B virus (HBV) infection.

Condition Intervention Phase
HBV
Chronic HBV Infections
Drug: TAF
Drug: TDF
Drug: TAF Placebo
Drug: TDF Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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:
  • Proportion of participants with hepatitis B e antigen (HBeAg) loss with seroconversion to antibody against HBeAb (anti-HBe) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Percent change from baseline in hip bone mineral density (BMD) at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
  • Percent change from baseline in spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
  • Change from baseline at Week 48 in serum creatinine [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]

Enrollment: 1022
Study Start Date: September 2013
Estimated Study Completion Date: November 2023
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAF
TAF + TDF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Drug: TAF
TAF 25 mg tablet administered orally once daily
Drug: TDF Placebo
TDF placebo tablet administered orally once daily
Active Comparator: TDF
TDF + TAF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Drug: TDF
TDF 300 mg tablet administered orally once daily
Other Name: Viread®
Drug: TAF Placebo
TAF placebo tablet administered orally once daily
Experimental: Open-label 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.
Drug: TAF
TAF 25 mg tablet administered orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • 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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01940471

  Hide Study Locations
Locations
United States, California
Asian Pacific Liver Center
Los Angeles, California, United States, 90057
Stanford University Medical Center
Palo Alto, California, United States, 94304
Huntington Medical Research Institutes
Pasadena, California, United States, 91105
Research and Education, Inc.
San Diego, California, United States, 92105
Silicon Valley Research Institute
San Jose, California, United States, 95128
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Maryland
Digestive Disease Associates, PA
Baltimore, Maryland, United States, 21229
United States, Massachusetts
Tufts Medical Center, Inc
Boston, Massachusetts, United States, 02111
United States, Michigan
Orlando Clinical
Detroit, Michigan, United States, 48202
United States, New York
Medical Procare, PLLC
Flushing, New York, United States, 11355
Sing Chan Private Practice
Flushing, New York, United States, 11355
United States, Pennsylvania
Jefferson Medical College of Thomas Jefferson
Philadelphia, Pennsylvania, United States, 19107
Xiaoli Ma, PC
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
The North Texas Research Institute
Arlington, Texas, United States, 76012
Kelsey Research Foundation
Houston, Texas, United States, 77005
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
St. Vincent's Hospital
Fitzroy, Victoria, Australia, 3065
Western Hospital- Footscray Hospital
Footscray, Victoria, Australia, 3011
Austin Health
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Australia
Royal Prince Alfred Hospital
Camperdown, Australia, 2050
Concord Repatriation General Hospital
Concord, Australia, 2137
Westmead Hospital Westmead
NSW, Australia, 2145
Bulgaria
Tokuda Hospital - Sofia
Sofia, Bulgaria, 1407
MHAT Alexandrovska Medical University, Sofia
Sofia, Bulgaria, 1431
MMA Hospital of Active Treatment
Sofia, Bulgaria, 1606
MHAT Sofia Med
Sofia, Bulgaria, 1797
Canada, Alberta
Heritage Medical Research Clinic
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta
Edmonton, Alberta, Canada, T6G 2X8
Canada, British Columbia
Liver and Intestinal Research Centre
Vancouver, British Columbia, Canada, V5Z 1H2
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
Dr.John Farley Inc.
Vancouver, British Columbia, Canada, V6A 4B6
Vancouver Infectious Disease Research and Care Centre
Vancouver, British Columbia, Canada, V6Z 2C7
Gastrointestinal Research Institute (GIRI)
Vancouver, British Columbia, Canada, V6Z 2K5
Canada, Manitoba
University of Manitoba, Health Sciences Center
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Ontario
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
University Health Network / Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8
Toronto Liver Centre
Toronto, Ontario, Canada, M6H 3M1
China, Guangdong
Guangzhou No.8 People's Hospital
Guangzhou, Guangdong, China, 510060
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China, 510515
The Third Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, China, 510630
China, Guangxi
The 1st Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, China, 530021
China, Guizhou
The Affiliated Hospital of Guiyang Medical College
Guiyang, Guizhou, China, 500000
China, Hainan
The People's Hospital of Hainan Province
Haikou, Hainan, China, 570311
China, Hebei
The 3rd Hospital of Hebei Medical University
Shijiazhuang, Hebei, China, 050051
China, Hong Kong
Princess Margaret Hospital
Kowloon, Hong Kong, China
Tuen Mun Hospital
Tuen Mun, Hong Kong, China
China, Hubei
Tongji Hospital, Tongji Medical college HuaZhong University of Science&Technology
Wuhan, Hubei, China, 430030
China, Hunan
XiangYa Hospital Central South University
Changsha, Hunan, China, 410008
The 2nd Xiangya Hospital Central South University
Changsha, Hunan, China, 410011
China, Jiangsu
Nanjing No. 2 Hospital
Nanjing, Jiangsu, China, 210003
Jiangsu Provincial People' Hospital
Nanjing, Jiangsu, China, 210029
China, Jiangxi
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China, 330000
China, Jilin
The First Hospital of Jilin University
Changchun, Jilin, China, 130021
China, Liaoning
The sixth People's Hospital of Shenyang
Shenyang, Liaoning, China, 110006
Shengjing Hospital of China Medical University
Shenyang, Liaoning, China, 110022
China, Shandong
Jinan Infectious Disease Hospital
Jinan, Shandong, China, 250021
China, Shanxi
First Affiliated Hospital of Xi'an Jiaotong
Xi'an, Shanxi, China, 710061
China, Sichuan
West China Hospital, Sichuan University
Chengdu, Sichuan, China, 610041
China, Yunnan
No.1 Hospital Affiliated to Kunming Medical College
Kunming, Yunnan, China, 650032
China
Beijing Ditan Hospital
Beijing, China, 100011
Peking University First Hospital
Beijing, China, 100034
PLA 302 Hospital
Beijing, China, 100039
Peking University People's Hospital
Beijing, China, 100044
Beijing Friendship Hospital, Capital Medical University
Beijing, China, 100050
Beijing You An Hospital,Capital Medical University
Beijing, China, 100069
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, China, 200025
Huashan Hospital, Fudan University
Shanghai, China, 200040
85 Hospital of People's Liberation Army
Shanghai, China, 200052
Renji Hospital Shanghai Jiaotong University School of Medicine
Shanghai, China, 200127
Shanghai Public Health Clinical Center
Shanghai, China, 201508
France
Hopital Beaujon
Clichy Cedex, France, 92110
Hopital Pitie Salpetriere
Paris, France, 75013
Hopital Civil de Strasbourg
Strasbourg, France, 67091
Service d'Hepatogastroenterologie
Vandoeuvre Les Nancy, France, 54511
Hopital Paul Brousse
Villejuif, France, 94800
Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Prince of Wales Hospital
Sha Tin, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
Tai Po, Hong Kong
India
Medanta-The Medicity
Gurgaon, Haryana, India, 122001
BYL Nair Hospital & T N Medical College
Mumbai, Maharashtra, India, 400008
Government Medical College and Superspecialty Hospital
Nagpur, Maharashtra, India, 440003
Midas Multispecialty Hospital
Nagpur, Maharashtra, India, 440010
Institute of Liver Diseases, HPB Surgery and Transplant Global Hospitals
Parel, Mumbai, India, 400 012
SMS Medical College & Hospital
Jaipur, Rajasthan, India, 302004
Postgraduate Institute of Medical Education & Research
Chandigarh, India, 160012
VGM Hospital
Coimbatore, India, 641005
Global Hospitals
Hyderabad, India, 500004
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals
Hyderabad, India, 500058
S.R. Kalla Hospital
Jaipur, India, 302001
Peerless Hospital & B.K.Roy Research Center
Kolkata, India, 700 094
Institute of Post Graduate Medical Education And Research
Kolkata, India, 700020
Seth GS Medical College and KEM Hospital
Mumbai, India, 400012
All India Institute of Medical Sciences
New Delhi, India, 110029
Sir Ganga Ram Hospital
New Delhi, India, 110060
Institute of Liver and Biliary Sciences
New Delhi, India, 110070
Nirmal Hospital
Surat, India, 395002
YR Gaitonde Centre for AIDS Research and Education Chennai
Taramani, India, 600113
Italy
Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
Bologna, Italy, 40138
Ospedali Riuniti Azienda Ospedaliera Universitaria di Foggia
Foggia, Italy, 71122
Azienda Ospedaliera Universitaria G. Martino
Messina, Italy, 98100
Azienda Ospedale San Paolo
Milano, Italy, 20142
Azienda Ospedaliera di Padova
Padova, Italy, 35100
Azienda Ospedaliera di Padova
Padova, Italy, 35128
Azienda Ospedaliero Universitaria Pisana
Pisa, Italy, 56124
Japan
Kyushu University Hospital
Fukuoka, Fukuoka-shi, Japan, 812-8582
Shin-Kokura Hospital
Fukuoka, Japan, 803-8505
National Hospital Organization Kyushu Medical Center
Fukuoka, Japan, 810-8563
Kobe City Medical Center General Hospital
Hyogo, Japan, 650-0047
Kagawa Prefectural Central Hospital
Kagawa, Japan, 760-0017
Yamanashi Prefectural Central Hospital
Kofu, Japan, 400-8506
Kurume University Hospital
Kurume, Japan, 830-0011
Kyoto Prefectural University of Medicine
Kyoto, Japan, 602-8566
Japan Red Cross Musashino Hospital
Musashino, Japan, 180-8610
Hyogo College of Medicine
Nishinomiya, Japan, 663-8501
Okayama University Hospital
Okayama, Japan, 700-8558
National Hospital Organization Nagasaki Medical Center
Omura, Japan, 856-8562
Osaka Red Cross Hospital
Osaka, Japan, 543-8555
Osaka University Hospital
Osaka, Japan, 545-8586
Hokkaido University Hospital
Sapporo, Japan, 060-8648
Medical Hospital of Tokyo Medical and Dental University
Tokyo, Japan, 113-8519
Korea, Republic of
Kosin University College of Medicine
Busan, Seo-gu, Korea, Republic of, 602702
Seoul National University Hospital
Seoul, South Korea, Korea, Republic of, 110-744
Pusan National University Hospital
Busan, Korea, Republic of, 602-739
SoonChunHyang University Hospital Cheonan
Cheonan, Korea, Republic of, 330-721
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of, 700-712
Kyungpook National University Hospital
Daegu, Korea, Republic of, 700-721
Konyang University Hospital
Daejeon, Korea, Republic of, 302-718
Inje University Ilsan Paik Hospital
Goyang-si, Korea, Republic of, 411-706
Seoul National University Bundang Hospital
Gyeonggi-Do, Korea, Republic of, 463-707
Yonsei University, Severance Hospital
Seoul, Korea, Republic of, 120-752
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Gangnam Severance Hospital
Seoul, Korea, Republic of, 135720
Seoul Saint Mary Hospital
Seoul, Korea, Republic of, 137-701
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Konkuk University Medical Center
Seoul, Korea, Republic of, 143-729
Korea University Guro Hospital
Seoul, Korea, Republic of, 152-703
Ajou University Hospital
Suwon, Korea, Republic of, 443-380
Ulsan University Hospital
Ulsan, Korea, Republic of, 682-714
Pusan National University Yangsan Hospital
Yangsan, Korea, Republic of, 626-770
New Zealand
Auckland Clinical Studies Limited
Grafton, Auckland, New Zealand, 1142
Waikato Hospital (District Health Board)
Hamilton, New Zealand, 2001
Poland
Wojewodzki Szpital Specjalistyczny im Dluskeigo
Bialystok, Poland, 15-540
Szpital Specjalistyczny
Chorzow, Poland, 41-500
Oddziak Obserwacyjno-Zakazny
Lodz, Poland, 91-347
SP ZOZ Wojewodzki Szpital Zakazny w Warszawie
Warszawa, Poland, 01-201
Klinika Chorob Zakaznych AM
Wroclaw, Poland, 50-349
Romania
Institutul National de Boli Infectioase Prof.Dr. Matei Bals
Bucharest, Bucuresti, Romania, 21105
Dr. Victor Babes Hospital for Infectious Diseases
Bucharest, Romania, 30303
Constanta Clinical Hosp. for Infectious Diseases (attn: Halikidis Stela, MD)
Constanta, Romania, 900708
Institutul de Gastroenterologie si Hepatologie lasi
Iasi, Romania, 700506
Russian Federation
Karaganda State Medical Institute
Koltsovo, Novosibirsk, Russian Federation, 630559
Sverdlovsk Regional Clinical Hospital #1
Ekaterinburg, Russian Federation, 620102
Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases
Lipetsk, Russian Federation, 398043
Research Institute of Nutrition (RAMS), Department of Gastroenterology and Hepatology
Moscow, Russian Federation, 109240
People's Friendship University of Russia
Moscow, Russian Federation, 117198
University Clinical Hospital #1
Moscow, Russian Federation, 119991
Limited Liability Company "Modern Medicine Clinic"
Moscow, Russian Federation, 121293
Novosobirsk State Medical University
Novosibirsk, Russian Federation, 630091
Institute of Clinical Immunology RAMS, Clinic of Immunopathology
Novosibirsk, Russian Federation, 630099
Municipal Clinical Hospital n.a. S.P. Botkin
Saint-Petersburg, Russian Federation, 191167
Research Institute of Influenza
Saint-Petersburg, Russian Federation, 197376
Medical Company Hepatology
Samara, Russian Federation, 443063
Singapore
National University Hospital Singapore
Singapore, Singapore, 119074
Singapore General Hospital
Singapore, Singapore, 169608
Changi General Hospital Pte Ltd.
Singapore, Singapore, 529889
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 8035
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 4103
Taiwan
Chiayi Christian Hospital
Chia-Yi, Taiwan, 60002
Hualien Tzu Chi Medical Center
Hualien, Taiwan, 970
Kaohsiung Med. College Hosp. Dept. of Internal Medicine
Kaohsiung, Taiwan, 80756
Far-Eastern Memorial Hospital
New Taipei City, Taiwan, 220
China Medical University Hospital
Taichung, Taiwan, 40447
National Cheng Kung University Hospital
Tainan, Taiwan, 70428
National Taiwan University Hospital
Taipei, Taiwan, 10002
Cathay General Hospital
Taipei, Taiwan, 11008
Turkey
Ankara University Medical Faculty Hospital
Ankara, Turkey, 6590
Dicle University Medical Faculty Department of Infectious Diseases
Diyarbakir, Turkey, 21280
University of Uludag
Gorukle-Bursa, Turkey, 16059
Istanbul Universitesi Cerrahpassa Tip Fakultesi Hastanesi
Istanbul, Turkey, 34098
Ege Universitesi Tip Fakultesi Hastanesi
Izmir, Turkey, 35040
United Kingdom
Barts & The London NHS Trust
London, United Kingdom, E1 1BB
Royal Free Hospital
London, United Kingdom, NW3 2QG
King's College Hospital
London, United Kingdom, SE5 9RS
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John Flaherty, PharmD Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01940471     History of Changes
Other Study ID Numbers: GS-US-320-0110 
Study First Received: August 20, 2013
Last Updated: April 25, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee
Canada: Ethics Review Committee
Canada: Health Canada
China: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
India: Drugs Controller General of India
Italy: The Italian Medicines Agency
Japan: Ministry of Health, Labor and Welfare
New Zealand: Medsafe
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Russia: Ministry of Health of the Russian Federation
Singapore: Ministry of Health
South Korea: Ministry of Food and Drug Safety
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Vietnam: Ministry of Health

Keywords provided by Gilead Sciences:
Hepatitis
Tenofovir
Viread

Additional relevant MeSH terms:
Hepatitis
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 22, 2016