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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:
ClinicalTrials.gov Identifier:
NCT01940341
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)-negative chronic hepatitis B virus (HBV) infection.

Condition Intervention Phase
HBV Chronic HIV 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-Negative, 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 ]
    The primary efficacy endpoint was determined by the achievement of HBV DNA < 29 IU/mL at Week 48.


Secondary Outcome Measures:
  • 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 in Serum Creatinine at Week 48 [ 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: 426
Actual Study Start Date: September 2013
Estimated Study Completion Date: January 2024
Primary Completion Date: September 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-320-0108 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 (NCT02836236) 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
  • 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)
  • 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): 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, 21228
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New Jersey
ID Care
Hillsborough, New Jersey, United States, 08844
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
Xiaoli Ma, PC
Philadelphia, Pennsylvania, United States, 19107
United States, Virginia
Hunter Holmes McGuire VA DVMC
Richmond, Virginia, United States, 23249
Australia, Victoria
Monash Medical Centre
Clayton, Victoria, Australia, 3168
St. Vincent's Hospital
Fitzroy, Victoria, Australia, 3065
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
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 4Z6
Zeidler Ledcor Centre Division of Gastroenterology
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
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, Ontario
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
Hôpital de la Croix Rousse
Lyon, France, 69004
Hopital Civil de Strasbourg- CHU Service
Strasbourg, France, 67091
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
India
Global Hospitals
Hyderabad, Andhra Pradesh, India, 500004
Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals
Hyderabad, Andhra Pradesh, India, 500058
Nirmal Hospital
Surat, Gujarat, India, 395002
Seth GS Medical College and KEM Hospital
Parel, Maharashtra, India, 400012
Global Hospital Super Specialty & Transplant Centre
Mumbai, Maharshtra, India, 400012
Postgraduate Institute of Medical Education and Research
Chandigarh, Punjab, India, 160012
S. R Kalla Memorial Gastro & General Hospital
Jaipur, Rajasthan, India, 302001
Institute of Post Graduate Medical Education And Research
Kolkata, West Bengal, India, 700020
All India Institute of Medical Sciences
New Delhi, India, 110029
Institute of Liver and Biliary Sciences
New Delhi, India, 110070
Italy
Azienda Ospedaliera S. Orsola − Malpighi
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria Ospedali
Foggia, Italy, 71122
Azienda Ospedaliero- Universitaria Pisana
Pisa, Italy, 56124
IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Italy, 71013
Japan
Kyushu University Hospital Fukuoka
Fukuoka, Japan, 812-8582
Shin-Kokura Hospital
Kitakyushu, Japan, 803-8505
Kobe City Medical Center General Hospital
Kobe, Japan, 650-0047
Kurume University Hospital
Kurume, Japan, 830-0011
Japan Red Cross Musashino Hospital
Musashino, Japan, 180-8610
The Hospital of Hyogo College of Medicine
Nishinomiya, Japan, 663-8501
National Hospital Organization Nagasaki Medical Center
Omura, Japan, 856-8562
Osaka Red Cross Hospital
Osaka, Japan, 543-8555
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
Korea, Republic of
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of, 700-712
Kyungpook National University Hospital
Daegu, Korea, Republic of, 700-721
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, 135-720
Seoul Saint Mary Hospital
Seoul, Korea, Republic of, 137-701
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Korea University Guro Hospital
Seoul, Korea, Republic of, 152-703
Chung-Ang University Hospital
Seoul, Korea, Republic of, 156-755
Pusan National University Yangsan Hospital
Yangsan, Korea, Republic of, 626-770
New Zealand
Auckland Clinical Studies Limited
Grafton, Auckland, New Zealand, 1142
Poland
Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika
Bialystok, Poland, 15-540
Szpital Specjalistyczny w Chorzowie Oddział
Chorzow, Poland, 41-500
SPZOZ, Wojewódzki Specjalistyczny Szpital
Lodz, Poland, 91-347
Centrum Badan Klinicznych - Przychodnia Badan
Wroclaw, Poland, 50-349
Romania
Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"
Bucuresti, Romania, 021105
Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"
Bucuresti, Romania, 030303
Institutul National de Boli Infectioase Prof.Dr. Matei Bals
Bucuresti, Romania, 21105
Spitatul Clinic de Boli Infectioase Constanta
Constanta, Romania, 900709
Gastromedica SRL
Iasi, Romania, 700506
Russian Federation
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
Novosibirsk State Medical University
Novosibirsk, Russian Federation, 630084
State Novosibirsk Regional Clinical Hospital
Novosibirsk, Russian Federation, 630087
Scientific Research Institute of Clinical Immunology
Novosibirsk, Russian Federation, 630099
Infection Center LLC Building 20, MSH #163 Territory Koltsovo
Novosibirsk, Russian Federation, 630559
Kirov Medical Military Academy
Saint-Petersburg, Russian Federation, 191124
Clinical Infectious Hospital named after S.P.Botkin
Saint-Petersburg, Russian Federation, 191167
Research Institute of Influenza
Saint-Petersburg, Russian Federation, 197376
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Taiwan
Hualien Tzu Chi Hospital
Hualien City, Taiwan, 970
Kaohsiung Medical University Hospital
Kaohsiung, Taiwan, 807
Taichung Veterans General Hospital
Taichung, Taiwan, 40705
National Cheng Kung University Hospital
Tainan, Taiwan, 70403
National Taiwan University Hospital
Taipei, Taiwan, 10002
Turkey
Dicle University Medical Faculty Department of Infectious Diseases
Diyarbakir, Diyarbakri, Turkey, 21280
Ankara Üniversitesi Gastroenteroloji Bilim Dalı Cebeci
Ankara, Turkey, 06100
Uludag Üniversitesi Tıp Fakültesi Gastroenteroloji
Bursa, Turkey, 16059
Istanbul Universitesi Cerrahpassa Tip Fakultesi Hastanesi
Istanbul, Turkey, 34098
Ege Universitesi Tip Fakultesi Hastanesi
Izmir, Turkey, 35100
United Kingdom
Barts and The London NHS Trust Royal London Hospital
London, United Kingdom, E1 1BB
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: NCT01940341     History of Changes
Other Study ID Numbers: GS-US-320-0108
2013-000626-63 ( 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
HIV Infections
Hepatitis B
Liver Diseases
Digestive System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Hepadnaviridae Infections
DNA Virus Infections
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