Back to resultsStudy to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
TAF
TDF
TAF Placebo
TDF Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B
Eligibility 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 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
TAF 25 mg
TDF 300 mg
Arm Description
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.
DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.
Outcomes
Primary Outcome Measures
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
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:
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
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
Secondary Outcome Measures
Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
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:
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
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
Percentage of Participants With HBV DNA Levels < 20 IU/mL at 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. Missing=Failure (M = F) approach was used for analysis.
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at 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.
Percentage of Participants With HBV DNA Levels < 20 IU/mL at 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.
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at 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.
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at 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.
Percentage of Participants With HBeAg Seroconversion at 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.
Percentage of Participants With HBeAg Loss at 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.
Percentage of Participants With HBeAg Seroconversion at 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.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 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.
Percentage of Participants With HBsAg Seroconversion at 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.
Percentage of Participants With HBsAg Loss at 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.
Percentage of Participants With HBsAg Seroconversion at 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.
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)
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.
Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)
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.
Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)
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.
Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)
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.
Change From Baseline in FibroTest® Score at 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.
Change From Baseline in FibroTest® Score at 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.
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Percent Change From Baseline in Hip BMD at Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Percent Change From Baseline in Spine BMD at Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Percent Change From Baseline in Spine BMD at Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at 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.
Change From Baseline in eGFR-CG at 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02979613
Brief Title
Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed
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) 25 mg QD in Subjects With Chronic Hepatitis B Who Are Virologically Suppressed
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
December 29, 2016 (Actual)
Primary Completion Date
September 10, 2018 (Actual)
Study Completion Date
January 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
490 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TAF 25 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
TDF 300 mg
Arm Type
Active Comparator
Arm Description
DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.
Intervention Type
Drug
Intervention Name(s)
TAF
Other Intervention Name(s)
Vemlidy®, GS-7340
Intervention Description
25 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
TDF
Other Intervention Name(s)
Viread®
Intervention Description
300 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
TAF Placebo
Intervention Description
Tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
TDF Placebo
Intervention Description
Tablet administered orally once daily
Primary Outcome Measure Information:
Title
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
Description
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:
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
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
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
Description
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:
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
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
Time Frame
Week 96
Title
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48
Description
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.
Time Frame
Weeks 48
Title
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96
Description
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.
Time Frame
Week 96
Title
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96
Description
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.
Time Frame
Week 96
Title
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With HBeAg Seroconversion at Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With HBeAg Loss at Week 96
Description
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.
Time Frame
Week 96
Title
Percentage of Participants With HBeAg Seroconversion at Week 96
Description
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.
Time Frame
Week 96
Title
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With HBsAg Seroconversion at Week 48
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With HBsAg Loss at Week 96
Description
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.
Time Frame
Week 96
Title
Percentage of Participants With HBsAg Seroconversion at Week 96
Description
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.
Time Frame
Week 96
Title
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)
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)
Description
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.
Time Frame
Week 96
Title
Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)
Description
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.
Time Frame
Week 96
Title
Change From Baseline in FibroTest® Score at Week 48
Description
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.
Time Frame
Baseline; Week 48
Title
Change From Baseline in FibroTest® Score at Week 96
Description
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.
Time Frame
Baseline; Week 96
Title
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Description
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Time Frame
Baseline; Week 48
Title
Percent Change From Baseline in Hip BMD at Week 96
Description
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Time Frame
Baseline; Week 96
Title
Percent Change From Baseline in Spine BMD at Week 48
Description
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Time Frame
Baseline; Week 48
Title
Percent Change From Baseline in Spine BMD at Week 96
Description
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Time Frame
Baseline; Week 96
Title
Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48
Description
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.
Time Frame
Baseline; Week 48
Title
Change From Baseline in eGFR-CG at Week 96
Description
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.
Time Frame
Baseline; Week 96
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Palo Alto
State/Province
California
Country
United States
City
Pasadena
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
San Jose
State/Province
California
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Novi
State/Province
Michigan
Country
United States
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
City
Flushing
State/Province
New York
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
New York
State/Province
New York
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Nashville
State/Province
Tennessee
Country
United States
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77478
Country
United States
City
Edmonton
Country
Canada
City
Toronto
Country
Canada
City
Vancouver
Country
Canada
City
Hong Kong
Country
Hong Kong
City
Kowloon
Country
Hong Kong
City
Milan
ZIP/Postal Code
20122
Country
Italy
City
Goyang
State/Province
Gyeonggi-d
Country
Korea, Republic of
City
Daegu
ZIP/Postal Code
700-721
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
03830
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
06973
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
152-703
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Barcelona
Country
Spain
City
Majadahonda
Country
Spain
City
Chiayi City
ZIP/Postal Code
60002
Country
Taiwan
City
Kaohsiung
Country
Taiwan
City
Taipei City
ZIP/Postal Code
10002
Country
Taiwan
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
Citations:
PubMed Identifier
32087795
Citation
Lampertico P, Buti M, Fung S, Ahn SH, Chuang WL, Tak WY, Ramji A, Chen CY, Tam E, Bae H, Ma X, Flaherty JF, Gaggar A, Lau A, Liu Y, Wu G, Suri V, Tan SK, Subramanian GM, Trinh H, Yoon SK, Agarwal K, Lim YS, Chan HLY. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patients with chronic hepatitis B: a randomised, double-blind, phase 3, multicentre non-inferiority study. Lancet Gastroenterol Hepatol. 2020 May;5(5):441-453. doi: 10.1016/S2468-1253(19)30421-2. Epub 2020 Feb 20.
Results Reference
result
Learn more about this trial
Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed
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