Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT01940471
Recruitment Status : Active, not recruiting
First Posted : September 12, 2013
Results First Posted : March 30, 2017
Last Update Posted : August 18, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE August 20, 2013
First Posted Date  ICMJE September 12, 2013
Results First Submitted Date  ICMJE December 9, 2016
Results First Posted Date  ICMJE March 30, 2017
Last Update Posted Date August 18, 2020
Actual Study Start Date  ICMJE September 2013
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL [ Time Frame: Week 48 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 9, 2013)
The proportion of participants with hepatitis B virus (HBV) DNA < 29 IU/mL [ Time Frame: Week 48 ]
The primary efficacy endpoint is determined by the achievement of HBV DNA < 29 IU/mL at Week 48.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2013)
  • 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 ]
  • Percent change from baseline at Week 48 in hip and spine bone mineral density (BMD) [ Time Frame: Baseline to Week 48 ]
  • Change From Baseline at Week 48 in Serum Creatinine [ Time Frame: Baseline to Week 48 ]
Current Other Pre-specified Outcome Measures
 (submitted: February 10, 2017)
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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Positive Hepatitis B
Official Title  ICMJE 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
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • HBV
  • Chronic HBV Infection
Intervention  ICMJE
  • Drug: TAF
    25 mg tablet administered orally once daily
    Other Names:
    • Vemlidy®
    • GS-7340
  • Drug: TDF
    300 mg tablet administered orally once daily
    Other Name: Viread®
  • Drug: TAF Placebo
    Tablet administered orally once daily
  • Drug: TDF Placebo
    Tablet administered orally once daily
Study Arms  ICMJE
  • Experimental: TAF 25 mg
    TAF + TDF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
    Interventions:
    • Drug: TAF
    • Drug: TDF Placebo
  • Active Comparator: TDF 300 mg
    TDF + TAF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
    Interventions:
    • Drug: TDF
    • Drug: TAF Placebo
  • 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.
    Intervention: Drug: TAF
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 23, 2016)
875
Original Estimated Enrollment  ICMJE
 (submitted: September 9, 2013)
864
Estimated Study Completion Date  ICMJE November 2023
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   France,   Hong Kong,   India,   Italy,   Japan,   Korea, Republic of,   New Zealand,   Poland,   Romania,   Russian Federation,   Singapore,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries China
 
Administrative Information
NCT Number  ICMJE NCT01940471
Other Study ID Numbers  ICMJE GS-US-320-0110
2013-000636-10 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP