Brief Summary
The primary objective of this study is to evaluate the non-inferiority of switching to a tenofovir alafenamide (TAF)-containing fixed dose combination (FDC) relative to maintaining tenofovir disoproxil fumarate (TDF)-containing combination regimens in virologically suppressed HIV-infected participants as determined by having HIV-1 RNA \< 50 copies/mL at Week 48.
Brief Title
Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Fixed Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Positive Participants
Categories
Completion Date
Completion Date Type
Actual
Conditions
HIV
HIV Infections
Eligibility Criteria
Key Inclusion Criteria:
* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study
* Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105
* Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA \< 50 copies/mL at the screening visit
* Normal echocardiograph (ECG)
* Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
* Hepatic transaminases (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) ≤ 5 × upper limit of the normal range (ULN)
* Direct bilirubin ≤ 1.5 x ULN
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
* Female participants who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
* Female participants who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
Key Exclusion Criteria:
* A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
* Hepatitis B surface antigen position
* Hepatitis C antibody positive
* Participants experiencing decompensated cirrhosis
* Females who are breastfeeding
* Positive serum pregnancy test
* Have an implanted defibrillator or pacemaker
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements
* Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial
* Participants receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), COBI, FTC, TDF, ATV, RTV, EFV, and TAF or participants with any known allergies to the excipients of E/C/F/TDF, E/C/F/TAF, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study
* Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105
* Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA \< 50 copies/mL at the screening visit
* Normal echocardiograph (ECG)
* Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
* Hepatic transaminases (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) ≤ 5 × upper limit of the normal range (ULN)
* Direct bilirubin ≤ 1.5 x ULN
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
* Female participants who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
* Female participants who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
Key Exclusion Criteria:
* A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
* Hepatitis B surface antigen position
* Hepatitis C antibody positive
* Participants experiencing decompensated cirrhosis
* Females who are breastfeeding
* Positive serum pregnancy test
* Have an implanted defibrillator or pacemaker
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements
* Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial
* Participants receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), COBI, FTC, TDF, ATV, RTV, EFV, and TAF or participants with any known allergies to the excipients of E/C/F/TDF, E/C/F/TAF, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study
* Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105
* Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA \< 50 copies/mL at the screening visit
* Normal echocardiograph (ECG)
* Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
* Hepatic transaminases (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) ≤ 5 × upper limit of the normal range (ULN)
* Direct bilirubin ≤ 1.5 x ULN
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
* Female participants who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
* Female participants who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
Inclusion/
* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving antiretroviral therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study
* Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105
* Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA \< 50 copies/mL at the screening visit
* Normal echocardiograph (ECG)
* Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
* Hepatic transaminases (aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) ≤ 5 × upper limit of the normal range (ULN)
* Direct bilirubin ≤ 1.5 x ULN
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens.
* Female participants who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
* Female participants who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
Inclusion/
Gender
All
Gender Based
false
Keywords
HIV
HIV 1 Infected
Virologically-Suppressed
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01815736
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-292-0109
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Open-Label Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Combination Single Tablet Regimen (STR) in Virologically-Suppressed, HIV-1 Positive Subjects
Primary Outcomes
Outcome Description
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Outcome Time Frame
Week 48
Secondary Ids
Secondary Id
2012-005114-20
Secondary Outcomes
Outcome Description
Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan. BMD is calculated as grams per square centimeter (g/cm\^2); the mean (SD) percentage change is presented.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Outcome Description
Spine BMD was assessed by DXA scan. BMD is calculated as g/cm\^2; the mean (SD) percentage change is presented.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Spine BMD at Week 48
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Change From Baseline in Serum Creatinine at Week 48
Outcome Description
The mean (SD) change of the overall EFV-related symptom assessment score is presented. The overall symptom score (ranging from 0 to 20) is the sum of the individual symptom scores ranging from 0 (no symptoms) to 4 (most severe symptoms) from the 5 EFV-related symptom assessments (dizziness, trouble sleeping, impaired concentration, sleepiness, and abnormal or vivid dream). A negative change from baseline indicates improvement.
EFV-Related Symptom Analysis Set: participants who received EFV/FTC/TDF as prior treatment, received at least 1 dose of study drug, and completed EFV-related symptom assessments at the baseline visit and at least 1 postbaseline visit.
EFV-Related Symptom Analysis Set: participants who received EFV/FTC/TDF as prior treatment, received at least 1 dose of study drug, and completed EFV-related symptom assessments at the baseline visit and at least 1 postbaseline visit.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Change From Baseline in the Overall EFV-related Symptom Assessment Score at Week 48
Outcome Description
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Outcome Time Frame
Week 96
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
Outcome Description
The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48
Outcome Description
The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Outcome Time Frame
Week 96
Outcome Measure
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96
Outcome Description
The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 48
Outcome Description
The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Change From Baseline in CD4 Cell Count at Weeks 96
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Grossberg
Investigator Email
rgrossbe@montefiore.org
Investigator Phone
718-920-5276