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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:
ClinicalTrials.gov Identifier:
NCT01940471
First Posted: September 12, 2013
Last Update Posted: September 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Gilead Sciences
  Purpose
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)-positive chronic hepatitis B virus (HBV) infection.

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
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:
  • Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL [ Time Frame: Week 48 ]

Secondary Outcome Measures:
  • Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48 [ Time Frame: Week 48 ]
  • Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 [ Time Frame: Baseline; Week 48 ]
  • Percent Change From Baseline in Spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ]
  • Change From Baseline at Week 48 in Serum Creatinine [ Time Frame: Baseline; Week 48 ]

Other Outcome Measures:
  • Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48 [ Time Frame: Up to 48 weeks ]
    Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method.


Enrollment: 875
Actual Study Start Date: August 2013
Estimated Study Completion Date: November 2023
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAF 25 mg
TAF + TDF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Drug: TAF
25 mg tablet administered orally once daily
Other Names:
  • Vemlidy®
  • GS-7340
Drug: TDF Placebo
Tablet administered orally once daily
Active Comparator: TDF 300 mg
TDF + TAF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Drug: TDF
300 mg tablet administered orally once daily
Other Name: Viread®
Drug: 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
25 mg tablet administered orally once daily
Other Names:
  • Vemlidy®
  • GS-7340

Detailed Description:
This study GS-US-320-0110 is an international study planned to enroll participants in global 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 cohorts were registered separately (NCT02836249) on ClinicalTrials.gov as these cohorts will not be part of the main study analysis.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Key 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

Key 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01940471


  Hide Study Locations
Locations
United States, California
Saint Vincent Medical Center Asia 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
Catonsville, Maryland, United States, 21228
United States, Massachusetts
Tufts Medical Center, Inc
Boston, Massachusetts, United States, 02111
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New York
New Discovery, LLC
Flushing, New York, United States, 11355
Sing Chan Private Practice
Flushing, New York, United States, 11355
United States, Pennsylvania
Jefferson Medical College
Philadelphia, Pennsylvania, United States, 19107
Xiaoli Ma, PC
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Texas Clinical Research Institute, LLC
Arlington, Texas, United States, 76012
Kelsey Research Foundation
Houston, Texas, United States, 77005
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Concord Repatriation General Hospital
Concord, New South Wales, Australia, 2137
Westmead Hospital Westmead
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Monash Medical Centre
Clayton, Victoria, Australia, 3168
St. Vincent's Hospital
Fitzroy, Victoria, Australia, 3065
Sunshine Hospital
Footscray, Victoria, Australia, 3011
Austin Health
Heidelberg, Victoria, Australia, 3084
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
The Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
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
University of Calgary
Calgary, Alberta, Canada, T2N 4Z6
Zeidler Ledcor Centre Division of Gastroenterology / Department of Medicine
Edmonton, Alberta, Canada, T6G 2X8
Canada, British Columbia
Liver and Intestinal Research Centre
Vancouver, British Columbia, Canada, V5Z 1H2
Gordon and Leslie Diamond Health Care Centre
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
Inspiration Research Limited
Toronto, Ontario, Canada, M5T 2S8
Toronto Liver Centre
Toronto, Ontario, Canada, M6H 3M1
France
Hopital Beaujon
Clichy Cedex, France, 92110
Hopital Pitie Salpetriere
Paris, France, 75651
Hopital Civil de Strasbourg
Strasbourg, France, 67091
Hopital Paul Brousse
Villejuif, France, 94804
Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Princess Margaret Hospital
Lai Chi Kok, Hong Kong
Prince of Wales Hospital
Sha Tin, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
Tai Po, Hong Kong
Tuen Mun Hospital
Tuen Mun, Hong Kong
India
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
SMS Medical College & Hospital
Jaipur, Rajasthan, India, 302004
Postgraduate Institute of Medical Education & Research
Chandigarh, India, 160012
YR Gaitonde Centre for AIDS Research and Education
Chennai, India, 600113
VGM Hospital
Coimbatore, India, 641005
Global Hospital
Hyderabad, India, 500004
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals
Hyderabad, India, 500058
S. R Kalla Memorial Gastro & General Hospital
Jaipur, India, 302001
Peerless Hospital & B.K.Roy Research Center
Kolkata, India, 700 094
Postgraduate Institute of Medical Education & 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
Global Hospital Super Specialty & Transplant Centre
Parel, India, 400 012
Nirmal Hospital
Surat, India, 395002
Italy
Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria Ospedali Riuniti di
Foggia, Italy, 71100
Policlinico Universitario G. Martino via Consolare
Messina, Italy, 98124
Azienda Ospedale San Paolo
Milano, Italy, 20142
Azienda Ospedaliera di Padova
Padova, Italy, 35100
Azienda Ospedaliera di Padova
Padova, Italy, 35121
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, 760-8557
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
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
Gyeonggi-do, Korea, Republic of, 411-706
Ajou University Hospital
Gyeonggi-do, Korea, Republic of, 443-380
Seoul National University Bundang Hospital
Gyeonggi-Do, Korea, Republic of, 463-707
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Severance Hospital Yonsei University Health System
Seoul, Korea, Republic of, 120-752
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Gangnam Severance Hospital
Seoul, Korea, Republic of, 135-720
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
SMG-SNU Boramae Medical Center
Seoul, Korea, Republic of, 156-707
Chung-Ang University Hospital
Seoul, Korea, Republic of, 156-755
Ulsan University Hospital
Ulsan, Korea, Republic of, 682-714
Yonsei Unversity Wonju
Wŏnju, Korea, Republic of, 220-701
Pusan National University Yangsan Hospital
Yangsan, Korea, Republic of, 626-770
New Zealand
Auckland Clinical Studies Limited
Auckland, New Zealand, 1142
Waikato Hospital (District Health Board)
Hamilton, New Zealand, 2001
Poland
Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika
Bialystok, Poland, 15-540
Szpital Specjalistyczny
Chorzow, Poland, 41-500
SPZOZ, Wojewódzki Specjalistyczny Szpital
Lodz, Poland, 91-347
SP ZOZ Wojewódzki Szpital Zakazny
Warszawa, Poland, 01-201
Centrum Badan Klinicznych
Wroclaw, Poland, 50-349
Romania
Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"
Bucharest, Romania, 030303
Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
Bucuresti, Romania, 021105
Spitatul Clinic de Boli Infectioase Constanta
Constanţa, Romania, 900709
Gastromedica SRL
Iasi, Romania, 700506
Spitalul Clinic Judetean de Urgenta Timisoara
Timişoara, Romania, 300736
Russian Federation
Lipetsk Regional Center for Prevention and Control of AIDS and Infectious Diseases
Lipetsk, Russian Federation, 398043
Scientific Research Institute of Nutrition
Moscow, Russian Federation, 115446
People's Friendship University of Russia
Moscow, Russian Federation, 117198
1st Moscow State Medical University University Clinical Hospital #3
Moscow, Russian Federation, 119435
Limited Liability Company "Modern Medicine Clinic"
Moscow, Russian Federation, 121170
Infectious Clinical Hospital #1 of Moscow Healthcare Department
Moscow, Russian Federation, 125367
Institute of Clinical Immunology RAMS, Clinic of Immunopathology
Novosibirsk, Russian Federation, 630084
Scientific Research Institute of Clinical Immunology
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
Sverdlovsk Regional Clinical Hospital #1
Yekaterinburg, Russian Federation, 620102
Singapore
National University Hospital Singapore
Singapore, Singapore, 119228
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
Chiayi, Taiwan, 60002
Hualien Tzu Chi Medical Center
Hualien, Taiwan, 970
Kaohsiung Med. College Hosp. Dept. of Internal Medicine
Kaohsiung, Taiwan, 80756
China Medical University Hospital
Taichung, Taiwan, 404
National Cheng Kung University Hospital
Tainan, Taiwan, 70403
National Taiwan University Hospital
Taipei, Taiwan, 10002
Cathay General Hospital
Taipei, Taiwan, 10630
Far-Eastern Memorial Hospital
Taipei, Taiwan, 220
Turkey
Ankara Üniversitesi Gastroenteroloji Bilim Dalı Cebeci
Ankara, Turkey, 06100
University of Uludag
Bursa, Turkey, 16059
Dicle University Medical Faculty Department of Infectious Diseases
Diyarbakir, Turkey, 21280
Istanbul Universitesi Cerrahpassa Tip Fakultesi Enfeksiyon
Istanbul, Turkey, 34098
Ege Universitesi Tip Fakultesi Hastanesi
Izmir, Turkey, 35100
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: Gilead Study Director Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01940471     History of Changes
Other Study ID Numbers: GS-US-320-0110
2013-000636-10 ( EudraCT Number )
First Submitted: August 20, 2013
First Posted: September 12, 2013
Results First Submitted: December 9, 2016
Results First Posted: March 30, 2017
Last Update Posted: September 15, 2017
Last Verified: September 2017

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