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Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed

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ClinicalTrials.gov Identifier: NCT02979613
Recruitment Status : Active, not recruiting
First Posted : December 1, 2016
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching to tenofovir alafenamide (TAF) versus continuing tenofovir disoproxil fumarate (TDF) in virologically suppressed adults with chronic hepatitis B virus (HBV) infection.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: TAF Drug: TDF Drug: TAF Placebo Drug: TDF Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 490 participants
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 Efficacy and Safety of Switching From Tenofovir Disoproxil Fumarate (TDF) 300 mg QD to Tenofovir Alafenamide (TAF) 25mg QD in Subjects With Chronic Hepatitis B Who Are Virologically Suppressed
Actual Study Start Date : December 29, 2016
Actual Primary Completion Date : September 10, 2018
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TAF
TAF + TDF placebo for 48 weeks
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
TDF + TAF placebo for 48 weeks
Drug: TDF
300 mg tablet administered orally once daily
Other Name: Viread®

Drug: TAF Placebo
Tablet administered orally once daily

Experimental: Open-Label Extension
Participants who complete 48 weeks of treatment are eligible for participation in the open-label extension period to receive TAF for an additional 48 weeks.
Drug: TAF
25 mg tablet administered orally once daily
Other Names:
  • Vemlidy®
  • GS-7340




Primary Outcome Measures :
  1. Proportion of Participants with HBV DNA ≥ 20 IU/mL at Week 48, as Determined by the Modified US FDA-Defined Snapshot Algorithm [ Time Frame: Week 48 ]

Secondary Outcome Measures :
  1. Proportion of Participants with HBV DNA ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm [ Time Frame: Week 96 ]
  2. Proportion of Participants with HBV DNA < 20 IU/mL (Target Detected/Not Detected) at Week 48, as Determined by the Modified US FDA-Defined Snapshot Algorithm [ Time Frame: Weeks 48 ]
  3. Proportion of Participants with HBV DNA < 20 IU/mL (Target Detected/Not Detected) at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm [ Time Frame: Week 96 ]
  4. Proportion of Participants with Hepatitis B e Antigen (HBeAg) Loss at Week 48 [ Time Frame: Week 48 ]
  5. Proportion of Participants with Seroconversion to Anti-Hepatitis B e-Antigen (Anti-HBe) at Week 48 [ Time Frame: Week 48 ]
  6. Proportion of Participants with HBeAg Loss at Week 96 [ Time Frame: Week 96 ]
  7. Proportion of Participants with Seroconversion to Anti-HBe at Week 96 [ Time Frame: Week 96 ]
  8. Proportion of Participants with Hepatitis B s Antigen (HBsAg) Loss at Week 48 [ Time Frame: Week 48 ]
  9. Proportion of Participants with Seroconversion to Anti-Hepatitis B s-Antigen (Anti-HBs) at Week 48 [ Time Frame: Week 48 ]
  10. Proportion of Participants with HBsAg Loss at Week 96 [ Time Frame: Week 96 ]
  11. Proportion of Participants with Seroconversion to Anti-HBs at Week 96 [ Time Frame: Week 96 ]
  12. Proportion of Participants with Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria) [ Time Frame: Week 48 ]
  13. Proportion of Participants with Normalized ALT at Week 48 (by Central Laboratory and AASLD criteria) [ Time Frame: Week 48 ]
  14. Proportion of Participants with Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria) [ Time Frame: Week 96 ]
  15. Proportion of Participants with Normalized ALT at Week 96 (by Central Laboratory and AASLD criteria) [ Time Frame: Week 96 ]
  16. Change from Baseline in Fibrosis as Assessed by FibroTest® at Week 48 [ Time Frame: Week 48 ]
  17. Change from Baseline in Fibrosis as Assessed by FibroTest® at Week 96 [ Time Frame: Week 96 ]
  18. Percent Change from Baseline in Hip Bone Mineral Density (BMD) at Week 48 [ Time Frame: Week 48 ]
  19. Percent Change from Baseline in Hip BMD at Week 96 [ Time Frame: Week 96 ]
  20. Percent Change from Baseline in Spine BMD at Week 48 [ Time Frame: Week 48 ]
  21. Percent Change from Baseline in Spine BMD at Week 96 [ Time Frame: Week 96 ]
  22. Change from Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at Week 48 [ Time Frame: Week 48 ]
  23. Change from Baseline in eGFR-CG at Week 96 [ Time Frame: Week 96 ]


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

Key Inclusion Criteria:

  • Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
  • Adult male and non-pregnant, non-lactating females
  • Documented evidence of chronic HBV infection previously
  • Maintained on TDF 300 mg QD for at least 48 weeks, and as monotherapy for chronic hepatitis B for at least 24 weeks with viral suppression (HBV DNA < LLOQ) for a minimum of 12 weeks prior to screening
  • Adequate renal function
  • Normal ECG

Key Exclusion Criteria:

  • Pregnant women or women 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 (HCV), hepatitis D virus (HDV), or HIV
  • Evidence of hepatocellular carcinoma
  • Current evidence of, or recent (≤ 5 year) history of clinical hepatic decompensation
  • Abnormal hematological and biochemical parameters, including:

    • Hemoglobin < 10 g/dL
    • Absolute neutrophil count < 750/mm^3
    • Platelets ≤ 50,000/mm^3
    • Aspartate aminotransferase (AST) or ALT > 5 × upper limit of the normal range (ULN)
    • Albumin < 3.0 mg/ dL
    • International normalized ratio (INR) > 1.5 × ULN (unless stable on anticoagulant regimen)
    • Total bilirubin > 2.5 × ULN
  • Received solid organ or bone marrow transplant
  • Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (eg, basal cell skin cancer). Individuals under evaluation for possible malignancy are not eligible.
  • Currently receiving therapy with immunomodulators (eg, corticosteroids), 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 compliance
  • Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.
  • Use of investigational agents within 3 months of screening, unless allowed by the sponsor

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


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): NCT02979613


  Show 39 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02979613     History of Changes
Other Study ID Numbers: GS-US-320-4018
2016-003632-20 ( EudraCT Number )
First Posted: December 1, 2016    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
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