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

August 24, 2020 updated by: Gilead Sciences

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) 25 mg QD in Subjects With Chronic Hepatitis B Who Are Virologically Suppressed

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

490

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Edmonton, Canada
      • Toronto, Canada
      • Vancouver, Canada
  • Hong Kong
      • Hong Kong, Hong Kong
      • Kowloon, Hong Kong
  • Italy
      • Milan, Italy, 20122
  • Korea, Republic of
      • Daegu, Korea, Republic of, 700-721
      • Seoul, Korea, Republic of
      • Seoul, Korea, Republic of, 135-710
      • Seoul, Korea, Republic of, 05505
      • Seoul, Korea, Republic of, 03722
      • Seoul, Korea, Republic of, 152-703
      • Seoul, Korea, Republic of, 06973
      • Seoul, Korea, Republic of, 03830
    • Gyeonggi-d
      • Goyang, Gyeonggi-d, Korea, Republic of
  • Spain
      • Barcelona, Spain
      • Majadahonda, Spain
  • Taiwan
      • Chiayi City, Taiwan, 60002
      • Kaohsiung, Taiwan
      • Taipei City, Taiwan, 10002
  • United Kingdom
      • London, United Kingdom
      • London, United Kingdom, E1 1BB
  • United States
    • California
      • Los Angeles, California, United States
      • Palo Alto, California, United States
      • Pasadena, California, United States
      • San Diego, California, United States
      • San Francisco, California, United States
      • San Jose, California, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Michigan
      • Novi, Michigan, United States
    • New York
      • Flushing, New York, United States
      • Flushing, New York, United States, 11355
      • New York, New York, United States
      • New York, New York, United States, 10029
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
      • Philadelphia, Pennsylvania, United States, 19107
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Sugar Land, Texas, United States, 77478

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 hepatitis B virus (HBV) infection previously
  • Maintained on tenofovir disoproxil fumarate (TDF) 300 mg once daily for at least 48 weeks, and as monotherapy for chronic hepatitis B for at least 24 weeks with viral suppression (HBV DNA < lower limit of quantitation) for a minimum of 12 weeks prior to screening
  • Adequate renal function
  • Normal Electrocardiogram

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 human immunodeficiency virus (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 alanine aminotransferase (ALT) > 5 × upper limit of the normal (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 TAF or TDF 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TAF 25 mg
Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 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 300 mg
DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.
Drug: TAF
25 mg tablet administered orally once daily
Other Names:
  • Vemlidy®
  • GS-7340
Drug: TDF
300 mg tablet administered orally once daily
Other Names:
  • Viread®
Drug: TAF Placebo
Tablet administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
Time Frame: Week 48

The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who:

  1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or

  2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and

    • Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or
    • Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
Time Frame: Week 96

The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 96 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who:

  1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 96 analysis window (from Day 589 to Day 840, inclusive), or

  2. Did not have on-treatment HBV DNA data available in the Week 96 analysis window and

    • Discontinued study drug prior to or in the Week 96 analysis window due to lack of efficacy, or
    • Discontinued study drug prior to or in the Week 96 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
Week 96
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48
Time Frame: Weeks 48
The percentage of participants with HBV DNA < 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. Missing=Failure (M = F) approach was used for analysis.
Weeks 48
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48
Time Frame: Week 48
The percentage of participants with HBV DNA < 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. The method of determining percentage of participants with HBV DNA levels <20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 48, was handled by M = F, and Missing=Excluded (M = E) approaches.
Week 48
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96
Time Frame: Week 96
The percentage of participants with HBV DNA < 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. M = F approach was used for analysis.
Week 96
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96
Time Frame: Week 96
The percentage of participants with HBV DNA < 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. The method of determining percentage of participants with HBV DNA levels <20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 96, was handled by Missing=Failure (M = F), and Missing=Excluded (M = E) approaches.
Week 96
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48
Time Frame: Week 48
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBeAg Seroconversion at Week 48
Time Frame: Week 48
HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBeAg Loss at Week 96
Time Frame: Week 96
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis.
Week 96
Percentage of Participants With HBeAg Seroconversion at Week 96
Time Frame: Week 96
HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 96
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Time Frame: Week 48
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBsAg Seroconversion at Week 48
Time Frame: Week 48
HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBsAg Loss at Week 96
Time Frame: Week 96
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis.
Week 96
Percentage of Participants With HBsAg Seroconversion at Week 96
Time Frame: Week 96
HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 96
Percentage 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
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 48
Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)
Time Frame: Week 48
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 48
Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)
Time Frame: Week 96
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 96
Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)
Time Frame: Week 96
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 96
Change From Baseline in FibroTest® Score at Week 48
Time Frame: Baseline; Week 48
The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Baseline; Week 48
Change From Baseline in FibroTest® Score at Week 96
Time Frame: Baseline; Week 96
The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Baseline; Week 96
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Time Frame: Baseline; Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 48
Percent Change From Baseline in Hip BMD at Week 96
Time Frame: Baseline; Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 96
Percent Change From Baseline in Spine BMD at Week 48
Time Frame: Baseline; Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 48
Percent Change From Baseline in Spine BMD at Week 96
Time Frame: Baseline; Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 96
Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48
Time Frame: Baseline; Week 48

Cockcroft-Gault formula is as follows:

  • For men: Glomerular filtration rate (GFR) = (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL)
  • For women: GFR = 0.85 * (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL).

Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Baseline; Week 48
Change From Baseline in eGFR-CG at Week 96
Time Frame: Baseline; Week 96

Cockcroft-Gault formula is as follows:

  • For men: Glomerular filtration rate (GFR) = (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL)
  • For women: GFR = 0.85 * (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL).

Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Baseline; Week 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 29, 2016

Primary Completion (Actual)

September 10, 2018

Study Completion (Actual)

January 30, 2020

Study Registration Dates

First Submitted

November 29, 2016

First Submitted That Met QC Criteria

November 29, 2016

First Posted (Estimate)

December 1, 2016

Study Record Updates

Last Update Posted (Actual)

September 14, 2020

Last Update Submitted That Met QC Criteria

August 24, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-320-4018
  • 2016-003632-20 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

IPD Sharing Time Frame

18 months after study completion

IPD Sharing Access Criteria

A secured external environment with username, password, and RSA code.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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