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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01940471
First received: August 20, 2013
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA < 29 IU/mL at Week 48.


Condition Intervention Phase
HBV
Chronic HBV Infections
Drug: Tenofovir alafenamide
Drug: Tenofovir disoproxil fumarate
Drug: Placebo to match tenofovir alafenamide
Drug: Placebo to match tenofovir DF
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:
  • The 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:
  • The 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 at Week 48 in hip and spine bone mineral density (BMD) [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
  • Change from baseline at Week 48 in serum creatinine [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 864
Study Start Date: September 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tenofovir alafenamide
Tenofovir alafenamide plus placebo to match tenofovir DF for 96 weeks, followed by open-label tenofovir alafenamide through Week 144.
Drug: Tenofovir alafenamide
Tenofovir alafenamide 25 mg tablet administered orally once daily
Drug: Placebo to match tenofovir DF
Placebo to match tenofovir DF administered as a tablet orally once daily
Active Comparator: Tenofovir disoproxil fumarate
Tenofovir DF plus placebo to match tenofovir alafenamide for 96 weeks, followed by open-label tenofovir alafenamide through Week 144.
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®
Drug: Placebo to match tenofovir alafenamide
Placebo to match tenofovir alafenamide administered as a tablet orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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 (CHB) infection
  4. 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)
  5. 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)
  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

Exclusion Criteria

  1. Females who are breastfeeding
  2. Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study
  3. Co-infection with hepatitis C, HIV or hepatitis D virus (HDV)
  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) > 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
  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

Contacts
Contact: Charlene Kranz TAF4HBV@gilead.com

  Hide Study Locations
Locations
United States, California
Asian Pacific Liver Center Recruiting
Los Angeles, California, United States, 90057
Peter J Ruane MD Inc Recruiting
Los Angeles, California, United States, 90036
Stanford University Medical Center Recruiting
Palo Alto, California, United States, 94304
Huntington Medical Research Institutes Recruiting
Pasadena, California, United States, 91105
Research and Education, Inc. Recruiting
San Diego, California, United States, 92105
Kaiser Permanente Recruiting
San Francisco, California, United States, 94118
Silicon Valley Research Institute Recruiting
San Jose, California, United States, 95128
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
United States, Maryland
Institute of Human Virology Recruiting
Baltimore, Maryland, United States, 21201
Digestive Disease Associates, PA Recruiting
Baltimore, Maryland, United States, 21229
United States, Michigan
Orlando Clinical Recruiting
Detroit, Michigan, United States, 48202
United States, New Jersey
ID Care Recruiting
Hillsborough, New Jersey, United States, 08844
United States, New York
Medical Procare, PLLC Recruiting
Flushing, New York, United States, 11355
Sing Chan Private Practice Recruiting
Flushing, New York, United States, 11355
United States, Pennsylvania
Xiaoli Ma, PC Recruiting
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
The North Texas Research Institute Recruiting
Arlington, Texas, United States, 76012
Kelsey Research Foundation Recruiting
Houston, Texas, United States, 77005
Research Specialists of Texas Recruiting
Houston, Texas, United States, 77030
United States, Virginia
Hunter Holmes McGuire VA DVAMC Recruiting
Richmond, Virginia, United States, 23298
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
St. Vincent's Hospital Recruiting
Fitzroy, Victoria, Australia, 3065
Western Hospital- Footscray Hospital Recruiting
Footscray, Victoria, Australia, 3011
Not yet recruiting
Footscray, Victoria, Australia, 3011
Austin Health Recruiting
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital Recruiting
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Sir Charles Gairdner Hospital Recruiting
Nedlands, Western Australia, Australia, 6009
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Australia
Royal Prince Alfred Hospital Recruiting
Camperdown, Australia, 2050
Concord Repatriation General Hospital Recruiting
Concord, Australia, 2137
Westmead Hospital Westmead Recruiting
NSW, Australia, 2145
Bulgaria
MHAT Sofia Med Recruiting
Sofia, Bulgaria, 1797
MHAT Alexandrovska Medical University, Sofia Recruiting
Sofia, Bulgaria, 1431
MMA Hospital of Active Treatment Recruiting
Sofia, Bulgaria, 1606
Canada, Alberta
Heritage Medical Research Clinic Recruiting
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2X8
Canada, British Columbia
Vancouver Infectious Disease Research and Care Centre Recruiting
Vancouver, British Columbia, Canada, V6Z 2C7
University of British Columbia Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Gastrointestinal Research Institute (GIRI) Recruiting
Vancouver, British Columbia, Canada, V6Z 2K5
Liver and Intestinal Research Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 1H2
Dr.John Farley Inc. Recruiting
Vancouver, British Columbia, Canada, V6A 4B6
Canada, Manitoba
University of Manitoba, Health Sciences Center Recruiting
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Ontario
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
University Health Network / Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Toronto Liver Centre Recruiting
Toronto, Ontario, Canada, M6H 3M1
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
China, Hong Kong
Princess Margaret Hospital Recruiting
Kowloon, Hong Kong, China
Tuen Mun Hospital Recruiting
Tuen Mun, Hong Kong, China
France
Hopital Beaujon Recruiting
Clichy Cedex, France, 92110
Hopital Henri Mondor Recruiting
Creteil Cedex, France, 94010
Hôpital de la Croix Rousse Recruiting
Lyon cedex, France, 04 69317
Hopital Pitie Salpetriere Recruiting
Paris, France, 75013
Hopital Civil de Strasbourg Recruiting
Strasbourg, France, 67091
Service d'Hepatogastroenterologie Recruiting
Vandoeuvre Les Nancy, France, 54511
Hopital Paul Brousse Recruiting
Villejuif, France, 94800
Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Prince of Wales Hospital Recruiting
Sha Tin, Hong Kong
Alice Ho Miu Ling Nethersole Hospital Recruiting
Tai Po, Hong Kong
India
Midas Multispecialty Hospital Recruiting
Nagpur, Maharashtra, India, 440010
PD Hinduja Hospital & Medical Research Center Recruiting
Mahim, Mumbai, India, 400016
Institute of Liver Diseases, HPB Surgery and Transplant Global Hospitals Recruiting
Parel, Mumbai, India, 400 012
MS Ramaiah Medical College and Hospital Recruiting
Bangalore, India, 560054
Not yet recruiting
Bangalore, India, 560017
Postgraduate Institute of Medical Education & Research Recruiting
Chandigarh, India, 160012
VGM Hospital Recruiting
Coimbatore, India, 641005
Not yet recruiting
Gurgaon, India, 122002
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals Recruiting
Hyderabad, India, 500058
Not yet recruiting
Hyderabad, India, 500082
Global Hospitals Recruiting
Hyderabad, India, 500004
Not yet recruiting
Jaipur, India, 302004
S.R. Kalla Hospital Recruiting
Jaipur, India, 302001
Lakeshore Hospital Recruiting
Kochi, India, 682040
Institute of Post Graduate Medical Education And Research Recruiting
Kolkata, India, 700020
Not yet recruiting
Lucknow, India, 226014
Not yet recruiting
Ludhiana, India, 141001
Seth GS Medical College and KEM Hospital Recruiting
Mumbai, India, 400012
Not yet recruiting
Mumbai, India, 400008
All India Institute of Medical Sciences Recruiting
New Delhi, India, 110029
Institute of Liver and Biliary Sciences Recruiting
New Delhi, India, 110070
Sir Ganga Ram Hospital Recruiting
New Delhi, India, 110060
Nirmal Hospital Recruiting
Surat, India, 395002
YR Gaitonde Centre for AIDS Research and Education Chennai Recruiting
Taramani, India, 600113
Italy
Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi Recruiting
Bologna, Italy, 40138
Ospedali Riuniti Azienda Ospedaliera Universitaria di Foggia Recruiting
Foggia, Italy, 71122
Azienda Ospedale San Paolo Recruiting
Milano, Italy, 20142
IRCCS Ospedale Maggiore Policlinico di Milano Recruiting
Milano, Italy, 20122
Azienda Ospedaliera di Padova Recruiting
Padova, Italy, 35128
Azienda Ospedaliero Universitaria Pisana Recruiting
Pisa, Italy, 56124
Casa Sollievodella Soferrenza IRCCS Recruiting
San Giovanni Rotondo, Italy, 71013
Japan
Shin-Kokura Hospital Recruiting
Fukuoka, Japan, 803-8505
National Hospital Organization Kyushu Medical Center Recruiting
Fukuoka, Japan, 810-8563
Kyushu University Hospital Fukuoka Recruiting
Fukuoka-shi, Japan, 812-8582
Kobe City Medical Center General Hospital Recruiting
Hyogo, Japan, 650-0047
Kohnodai Hospital, National Center for Global Health and Medicine Recruiting
Ichikawa, Japan, 272-0827
Kagawa Prefectural Central Hospital Recruiting
Kagawa, Japan, 760-0017
Yamanashi Prefectural Central Hospital Recruiting
Kofu, Japan, 400-8506
Kurume University Hospital Recruiting
Kurume, Japan, 830-0011
Kyoto Prefectural University of Medicine Recruiting
Kyoto, Japan, 602-8566
Japan Red Cross Musashino Hospital Recruiting
Musashino, Japan, 180-8610
Hyogo College of Medicine Recruiting
Nishinomiya, Japan, 663-8501
Okayama University Hospital Recruiting
Okayama, Japan, 700-8558
National Hospital Organization Nagasaki Medical Center Recruiting
Omura, Japan, 856-8562
Osaka University Hospital Recruiting
Osaka, Japan, 545-8586
Osaka Red Cross Hospital Recruiting
Osaka, Japan, 543-8555
Kinki University Hospital Recruiting
Osaka, Japan, 589-8511
Hokkaido University Hospital Recruiting
Sapporo, Japan, 060-8648
Osaka University Hospital Recruiting
Suita, Japan, 565-0871
Medical Hospital of Tokyo Medical and Dental University Recruiting
Tokyo, Japan, 113-8519
Yamagata University Hospital Recruiting
Yamagata, Japan, 990-9585
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, South Korea, Korea, Republic of, 110-744
Pusan National University Hospital Recruiting
Busan, Korea, Republic of, 602-739
SoonChunHyang University Hospital Cheonan Recruiting
Cheonan, Korea, Republic of, 330-721
Keimyung University Dongsan Medical Center Recruiting
Daegu, Korea, Republic of, 700-712
Kyungpook National University Hospital Recruiting
Daegu, Korea, Republic of, 700-721
Inje University Ilsan Paik Hospital Recruiting
Goyang-si, Korea, Republic of, 411-706
Seoul National University Bundang Hospital Recruiting
Gyeonggi-Do, Korea, Republic of, 463-707
Seoul Saint Mary Hospital Recruiting
Seoul, Korea, Republic of, 137-701
Korea University Guro Hospital Recruiting
Seoul, Korea, Republic of, 152-703
Yonsei University, Severance Hospital Recruiting
Seoul, Korea, Republic of, 120-752
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 135-710
Konkuk University Medical Center Recruiting
Seoul, Korea, Republic of, 143-729
Gangnam Severance Hospital Recruiting
Seoul, Korea, Republic of, 135720
Ajou University Hospital Recruiting
Suwon, Korea, Republic of, 443-380
Pusan National University Yangsan Hospital Recruiting
Yangsan, Korea, Republic of, 626-770
New Zealand
Auckland Clinical Studies Limited Recruiting
Grafton, Auckland, New Zealand, 1142
Waikato Hospital (District Health Board) Recruiting
Hamilton, New Zealand, 2001
The Hepatitis Foundation of New Zealand Recruiting
Whakatane, New Zealand, 3120
Poland
Wojewodzki Szpital Specjalistyczny im Dluskeigo Recruiting
Bialystok, Poland, 15-540
Szpital Specjalistyczny Recruiting
Chorzow, Poland, 41-500
Oddziak Obserwacyjno-Zakazny Recruiting
Lodz, Poland, 91-347
Klinika Chorob Zakaznych AM Recruiting
Wroclaw, Poland, 50-349
Romania
Institutul National de Boli Infectioase Prof.Dr. Matei Bals Recruiting
Bucharest, Bucuresti, Romania, 21105
Dr. Victor Babes Hospital for Infectious Diseases Recruiting
Bucharest, Romania, 30303
Gastromond SRL Recruiting
Constanta, Romania, 900635
Constanta Clinical Hosp. for Infectious Diseases (attn: Halikidis Stela, MD) Recruiting
Constanta, Romania, 900708
Institutul de Gastroenterologie si Hepatologie lasi Recruiting
Iasi, Romania, 700506
Spitalul Clinic Judetean de Urgenta Timisoara Recruiting
Timisoara, Romania, 300736
Russian Federation
Karaganda State Medical Institute Recruiting
Koltsovo, Novosibirsk, Russian Federation, 630559
Chita State Medical Academy, Curative-Diagnostic Clinic Recruiting
Chita, Russian Federation, 672039
Research Institute of Nutrition (RAMS), Department of Gastroenterology and Hepatology Recruiting
Moscow, Russian Federation, 109240
University Clinical Hospital #1 Recruiting
Moscow, Russian Federation, 119991
Limited Liability Company "Modern Medicine Clinic" Recruiting
Moscow, Russian Federation, 121293
Institute of Clinical Immunology RAMS, Clinic of Immunopathology Recruiting
Novosibirsk, Russian Federation, 630099
Novosobirsk State Medical University Recruiting
Novosibirsk, Russian Federation, 630091
Municipal Clinical Hospital n.a. S.P. Botkin Recruiting
Saint-Petersburg, Russian Federation, 191167
Research Institute of Influenza Recruiting
Saint-Petersburg, Russian Federation, 197376
Singapore
Singapore General Hospital Recruiting
Singapore, Singapore, 169608
Spain
Hospital Alcorcón Recruiting
Alcorcon, Spain, 28922
Hospital Germans Trias i Pujol Recruiting
Badalona, Spain, 8916
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 8035
Hospital Universitario Puerta de Hierro Recruiting
Majadahonda, Spain, 28020
Hospital Universitario Virgen del Rocio Recruiting
Sevilla, Spain, 4103
Hospital Universitario de Valme Recruiting
Sevilla, Spain, 41014
Hospital La Fe Recruiting
Valencia, Spain, 46026
Taiwan
Chiayi Christian Hospital Recruiting
Chia-Yi, Taiwan, 60002
Hualien Tzu Chi Medical Center Recruiting
Hualien, Taiwan, 970
Kaohsiung Med. College Hosp. Dept. of Internal Medicine Recruiting
Kaohsiung, Taiwan, 80756
Far-Eastern Memorial Hospital Recruiting
New Taipei City, Taiwan, 220
China Medical University Hospital Recruiting
Taichung, Taiwan, 40447
National Cheng Kung University Hospital Recruiting
Tainan, Taiwan, 70428
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 10002
Cathay General Hospital Recruiting
Taipei, Taiwan, 11008
Turkey
Ankara University Medical Faculty Hospital Recruiting
Ankara, Turkey, 6590
Dicle University Medical Faculty Department of Infectious Diseases Recruiting
Diyarbakir, Turkey, 21280
University of Uludag Recruiting
Gorukle-Bursa, Turkey, 16059
Istanbul Universitesi Cerrahpassa Tip Fakultesi Hastanesi Recruiting
Istanbul, Turkey, 34098
Ege Universitesi Tip Fakultesi Hastanesi Recruiting
Izmir, Turkey, 35040
United Kingdom
Royal Free Hospital Recruiting
London, United Kingdom, NW3 2QG
King's College Hospital Recruiting
London, United Kingdom, SE5 9RS
Barts & The London NHS Trust Recruiting
London, United Kingdom, E1 1BB
Nottingham University Hospitals NHS Trust Recruiting
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John Flaherty, PharmD Gilead Sciences
  More Information

No publications provided

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: August 20, 2014
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 A
Hepatitis B
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 14, 2014