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

This study is currently recruiting participants.
Verified April 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01940341
First received: August 20, 2013
Last updated: April 7, 2014
Last verified: April 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01940341

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
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
University California San Francisco (UCSF) Recruiting
San Francisco, California, United States, 94110
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
Withdrawn
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
Not yet recruiting
Houston, Texas, United States, 77005
United States, Virginia
Hunter Holmes McGuire VA DVAMC Recruiting
Richmond, Virginia, United States, 23298
Not yet recruiting
Richmond, Virginia, United States, 23249
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Austin Health Recruiting
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital Recruiting
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Australia
St. Vincent's Hospital Recruiting
Fitzroy, Australia, 3065
Sir Charles Gairdner Hospital Recruiting
Nedlands, Australia, 6009
Canada, Alberta
Heritage Medical Research Clinic Recruiting
Calgary, Alberta, Canada, T2N 4Z6
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2X8
Canada, British Columbia
Gastrointestinal Research Institute (GIRI) Recruiting
Vancouver, British Columbia, Canada, V6Z 2K5
University of British Columbia Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Vancouver Infectious Disease Research and Care Centre Recruiting
Vancouver, British Columbia, Canada, V6Z 2C7
Liver and Intestinal Research Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 1H2
Canada, Manitoba
University of Manitoba, Health Science Center Recruiting
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Ontario
Not yet 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
France
Not yet recruiting
Strasbourg, Alsace, France, 67091
Not yet recruiting
Lyon, Rhône-Alpes, France, 69317
Hopital Beaujon Recruiting
Clichy Cedex, France, 92110
Hopital Pitie Salpetriere Recruiting
Paris, France, 75013
Hopital Paul Brousse Recruiting
Villejuif, France, 94800
Hopital Henri Mondor Recruiting
Créteil Cedex, Île-de-France, France, 94010
Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Prince of Wales Hospital Recruiting
Sha Tin, Hong Kong
India
Not yet recruiting
Hyderabad, Andhra Pradesh, India, 500082
Not yet recruiting
Mumbai, Maharashtra, India, 400012
Not yet recruiting
Ludhiana, Punjab, India, 141001
Institute of Post Graduate Medical Education And Research Recruiting
Kolkata, West Bengal, India, 700020
Not yet recruiting
Chandigath, India, 160012
Not yet recruiting
Coimbatore, India, 641005
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals Recruiting
Hyderabad, India, 500058
Not yet recruiting
Lucknow, India, 226014
Not yet recruiting
Mumbai, India, 400012
Midas Multispecialty Hospital Recruiting
Nagpur, India, 440010
Not yet recruiting
New Delhi, India, 110070
Not yet recruiting
New Delhi, India, 110029
Nirmal Hospital Recruiting
Surat, India, 395002
Italy
Not yet recruiting
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria Pisana Recruiting
Cisanello Pisa, Italy, 56124
IRCCS Ospedale Maggiore Policlinico di Milano Recruiting
Milano, Italy, 20122
Casa Sollievodella Soferrenza IRCCS Recruiting
San Giovanni Rotondo, Italy, 71013
Japan
National Hospital Organization Nagasaki Medical Center Recruiting
Omura, Japan, 856-8562
Hokkaido University Hospital Recruiting
Sapporo, Japan, 060-8648
Korea, Republic of
Not yet recruiting
Gangnam-gu, Korea, Republic of, 135-720
Seoul Saint Mary Hospital Recruiting
Seoul, Korea, Republic of, 137-701
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
New Zealand
Auckland Clinical Studies Limited Recruiting
Grafton, Auckland, New Zealand, 1142
Romania
Gastromond SRL Recruiting
Constanta, Romania, 900635
Russian Federation
Karaganda State Medical Institute Recruiting
Koltsovo, Novosibirsk, Russian Federation, 630559
State fiscal health agency of Moscow "Infectious Clinical Hospital 1 Moscow Health Department" Recruiting
Moscow, Russian Federation, 125367
Limited Liability Company "Modern Medicine Clinic" Recruiting
Moscow, Russian Federation, 121293
Novosobirsk State Medical University Recruiting
Novosibirsk, Russian Federation, 630091
Institute of Clinical Immunology RAMS, Clinic of Immunopathology Recruiting
Novosibirsk, Russian Federation, 630099
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 8035
Hospital Universitario Puerta de Hierro Recruiting
Majadahonda, Spain, 28020
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 10002
Turkey
Ankara University Medical Faculty Hospital Recruiting
Ankara, Turkey, 6590
University of Uludag Recruiting
Gorukle-Bursa, Turkey, 16059
United Kingdom
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: NCT01940341     History of Changes
Other Study ID Numbers: GS-US-320-0108
Study First Received: August 20, 2013
Last Updated: April 7, 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 April 15, 2014