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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01940341
First received: August 20, 2013
Last updated: September 25, 2014
Last verified: September 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 DF
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-Negative, 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:
  • Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
  • Change from baseline in serum creatinine at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 390
Study Start Date: September 2013
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: August 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 DF
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 DF
Tenofovir DF 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. 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)
  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
  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: NCT01940341

  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
University California San Francisco (UCSF)
San Francisco, California, United States, 94110
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, Michigan
Orlando Clinical
Detroit, Michigan, United States, 48202
United States, New Jersey
ID Care
Hillsborough, New Jersey, United States, 08844
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
Xiaoli Ma, PC
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
The North Texas Research Institute
Arlington, Texas, United States, 76012
United States, Virginia
Hunter Holmes McGuire VA DVMC
Richmond, Virginia, United States, 23249
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Monash Medical Centre
Clayton, Victoria, Australia, 3168
Western Hospital- Footscray Hospital
Footscray, Victoria, Australia, 3011
Austin Health
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Australia
St. Vincent's Hospital
Fitzroy, Australia, 3065
Sir Charles Gairdner Hospital
Nedlands, Australia, 6009
Canada, Alberta
Heritage Medical Research Clinic
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta
Edmonton, Alberta, Canada, T6G 2X8
Canada, British Columbia
Vancouver Infectious Disease Research and Care Centre
Vancouver, British Columbia, Canada, V6Z 2C7
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
Gastrointestinal Research Institute (GIRI)
Vancouver, British Columbia, Canada, V6Z 2K5
Liver and Intestinal Research Centre
Vancouver, British Columbia, Canada, V5Z 1H2
Dr. John Farley Inc.
Vancouver, British Columbia, Canada, V6A 4B6
Canada, Manitoba
University of Manitoba, Health Science Center
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Ontario
University Health Network / Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Toronto Liver Centre
Toronto, Ontario, Canada, M6H 3M1
Toronto Western Hospital
Toronto, Ontario, Canada, M5T 2S8
China, Hong Kong
Princess Margaret Hospital
Kowloon, Hong Kong, China
France
Hopital Civil de Strasbourg
Strasbourg, Alsace, France, 67091
Hôpital de la Croix Rousse
Lyon, Rhône-Alpes, France, 69317
Hopital Beaujon
Clichy Cedex, France, 92110
Hopital Pitie Salpetriere
Paris, France, 75013
Hopital Paul Brousse
Villejuif, France, 94800
Hopital Henri Mondor
Créteil Cedex, Île-de-France, France, 94010
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
Hyderabad, Andhra Pradesh, India, 500082
Global Hospitals
Hyderabad, Andhra Pradesh, India, 500004
Sir Ganga Ram Hospital
Rajinder Nagar, Delhi, India, 110060
Medanta-The Medicity
Gurgaon, Haryana, India, 122001
MS Ramaiah Medical College and Hospital
Bangalore, Karnataka, India, 560054
Institute of Liver Diseases, HPB Surgery and Transplant Global Hospitals
Parel, Maharashtra, India, 400012
Seth GS Medical College and KEM Hospital
Mumbai, Maharastra, India, 400012
Dayanand Medical College & Hospital
Ludhiana, Punjab, India, 141001
Institute of Post Graduate Medical Education And Research
Kolkata, West Bengal, India, 700020
Postgraduate Institute of Medical Education and Research
Chandigarh, India, 160012
Coimbatore, India, 641005
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals
Hyderabad, India, 500058
S.R. Kalla Hospital
Jaipur, India, 302001
Lucknow, India, 226014
Midas Multispecialty Hospital
Nagpur, India, 440010
Institute of Liver and Biliary Sciences
New Delhi, India, 110070
All India Institute of Medical Sciences
New Delhi, India, 110029
Nirmal Hospital
Surat, India, 395002
Italy
Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria Pisana
Cisanello Pisa, Italy, 56124
Ospedali Riuniti Azienda Ospedaliera Universitaria di Foggia
Foggia, Italy, 71122
Azienda Ospedale San Paolo
Milano, Italy, 20142
IRCCS Ospedale Maggiore Policlinico di Milano
Milano, Italy, 20122
Casa Sollievodella Soferrenza IRCCS
San Giovanni Rotondo, Italy, 71013
Japan
Shin-Kokura Hospital
Fukuoka, Japan, 803-8505
National Hospital Organization Kyushu Medical Center
Fukuoka, Japan, 810-8563
Kyushu University Hospital Fukuoka
Fukuoka-shi, Japan, 812-8582
Kobe City Medical Center General Hospital
Hyogo, Japan, 650-0047
Kohnodai Hospital, National Center for Global Health and Medicine
Ichikawa, Japan, 272-0827
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
Kinki University Hospital
Osaka, Japan, 589-8511
Osaka University Hospital
Osaka, Japan, 545-8586
Hokkaido University Hospital
Sapporo, Japan, 060-8648
Osaka University Hospital
Suita, Japan, 565-0871
Medical Hospital of Tokyo Medical and Dental University
Tokyo, Japan, 113-8519
Yamagata University Hospital
Yamagata, Japan, 990-9585
Korea, Republic of
SoonChunHyang University Hospital Cheonan
Cheonan, Chungcheongnam-Do, Korea, Republic of, 330-721
Pusan National University Yangsan Hospital
Yangsan, Gyeongsangnam-do, Korea, Republic of
Pusan National University Hospital
Busan, Korea, Republic of, 602-739
Kyungpook National University Hospital
Daegu, Korea, Republic of, 700-721
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of, 700-712
Gangnam-gu, Korea, Republic of, 135-720
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Seoul Saint Mary Hospital
Seoul, Korea, Republic of, 137-701
Korea University Guro Hospital
Seoul, Korea, Republic of, 152-703
Yonsei University, Severance Hospital
Seoul, Korea, Republic of, 120-752
Asan Medical Center
Seoul, Korea, Republic of, 138-736
New Zealand
Auckland Clinical Studies Limited
Grafton, Auckland, New Zealand, 1142
Poland
Wojewodzki Szpital Specjalistyczny im Dluskeigo
Bialystok, Poland, 15-540
Wojewodzki Szpital Obserwacyjno-Zakazny im. T. Browicza
Bydgoszcz, Poland, 85-030
Szpital Specjalistyczny
Chorzow, Poland, 41-500
Oddziak Obserwacyjno-Zakazny
Lodz, Poland, 91-347
Klinika Chorob Zakaznych AM
Wroclaw, Poland, 50-349
Romania
Institutul National de Boli Infectioase Prof.Dr. Matei Bals
Bucharest, Bucuresti, Romania, 21105
Gastromond SRL
Constanta, Romania, 900635
Constanta Clinical Hosp. for Infectious Diseases (attn: Halikidis Stela, MD)
Constanta, Romania, 900708
Institutul de Gastroenterologie si Hepatologie lasi
Iasi, Romania, 700506
Spitalul Clinic Judetean de Urgenta Timisoara
Timisoara, Romania, 300736
Russian Federation
Karaganda State Medical Institute
Koltsovo, Novosibirsk, Russian Federation, 630559
Research Institute of Nutrition (RAMS), Department of Gastroenterology and Hepatology
Moscow, Russian Federation, 109240
University Clinical Hospital #1
Moscow, Russian Federation, 119991
Limited Liability Company "Modern Medicine Clinic"
Moscow, Russian Federation, 121293
State fiscal health agency of Moscow "Infectious Clinical Hospital 1 Moscow Health Department"
Moscow, Russian Federation, 125367
Novosobirsk State Medical University
Novosibirsk, Russian Federation, 630091
Institute of Clinical Immunology RAMS, Clinic of Immunopathology
Novosibirsk, Russian Federation, 630099
State Budgetary Healthcare Institution "State Novosibirsk Regional Clinical Hospital"
Novosibirsk, Russian Federation, 630087
Research Institute of Influenza
Saint-Petersburg, Russian Federation, 197376
Federal State Budget Military Educational Institution Medical Military Academy n. a. S. M. Kirov
Saint-Petersburg, Russian Federation, 194044
Municipal Clinical Hospital n.a. S.P. Botkin
Saint-Petersburg, Russian Federation, 191167
Singapore
National University Hospital Singapore
Singapore, Singapore, 119074
Changi General Hospital Pte Ltd.
Singapore, Singapore, 529889
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 8035
Hospital Universitario Puerta de Hierro
Majadahonda, Spain, 28020
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 4103
Taiwan
Hualien Tzu Chi Medical Center
Hualien, Taiwan, 970
Kaohsiung Med. College Hosp. Dept. of Internal Medicine
Kaohsiung, Taiwan, 80756
Taichung Veterans General Hospital
Taichung, Taiwan, 40705
National Cheng Kung University Hospital
Tainan, Taiwan, 70428
National Taiwan University Hospital
Taipei, Taiwan, 10002
Turkey
Dicle University Medical Faculty Department of Infectious Diseases
Diyarbakir, Diyarbakri, Turkey, 21280
Ankara University Medical Faculty Hospital
Ankara, Turkey, 6590
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
Royal Free Hospital
London, United Kingdom, NW3 2QG
King's College Hospital
London, United Kingdom, SE5 9RS
Barts & The London NHS Trust
London, United Kingdom, E1 1BB
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

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01940341     History of Changes
Other Study ID Numbers: GS-US-320-0108
Study First Received: August 20, 2013
Last Updated: September 25, 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
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
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 October 01, 2014