Study to Evaluate the Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Positive, Antiretroviral Treatment-Naive Adults

Brief Summary
The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) FDC in HIV-1 positive, antiretroviral treatment-naive adults.
Brief Title
Study to Evaluate the Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Positive, Antiretroviral Treatment-Naive Adults
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
* Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
* No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PREP) or post-exposure prophylaxis (PEP), up to 6 months prior to screening
* Screening genotype report must show sensitivity to elvitegravir, emtricitabine, tenofovir disoproxil fumarate (tenofovir DF)
* Normal electrocardiogram (ECG)
* Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Males and 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 30 days following the last dose of study drug
* Females 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
* Females 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 (HBsAg) positive
* Hepatitis C antibody positive
* Individuals 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 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 individual unsuitable for the study or unable to comply with dosing requirements
* Participation in any other clinical trial (including observational trials) without prior approval
* Individuals receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or individuals with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF single-tablet regimen tablets

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
* Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
* No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PREP) or post-exposure prophylaxis (PEP), up to 6 months prior to screening
* Screening genotype report must show sensitivity to elvitegravir, emtricitabine, tenofovir disoproxil fumarate (tenofovir DF)
* Normal electrocardiogram (ECG)
* Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Males and 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 30 days following the last dose of study drug
* Females 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
* Females 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
Treatment Naive
HIV 1 Infected
Female
Women
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01780506
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-292-0104
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults
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
2012-004458-27
Secondary Outcomes
Outcome Description
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Weeks 96 and 144 were 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
Weeks 96 and 144
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 and 144
Outcome Description
The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Weeks 48, 96, and 144 were 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
Weeks 48, 96. and 144
Outcome Measure
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48, 96, and 144
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Change From Baseline in CD4+ Cell Count at Week 48
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Change From Baseline in CD4+ Cell Count at Week 96
Outcome Time Frame
Baseline; Week 144
Outcome Measure
Change From Baseline in CD4+ Cell Count at Week 144
Outcome Description
Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Outcome Description
Hip BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Percent Change From Baseline in Hip BMD at Week 96
Outcome Description
Hip BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 144
Outcome Measure
Percent Change From Baseline in Hip BMD at Week 144
Outcome Description
Spine BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Spine BMD at Week 48
Outcome Description
Spine BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Percent Change From Baseline in Spine BMD at Week 96
Outcome Description
Spine BMD was assessed by DXA scan.
Outcome Time Frame
Baseline; Week 144
Outcome Measure
Percent Change From Baseline in Spine BMD at Week 144
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Change From Baseline in Serum Creatinine at Week 48
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Change From Baseline in Serum Creatinine at Week 96
Outcome Time Frame
Baseline; Week 144
Outcome Measure
Change From Baseline in Serum Creatinine at Week 144
Outcome Description
Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Outcome Time Frame
Up to 48 weeks
Outcome Measure
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 48
Outcome Description
Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Outcome Time Frame
Up to 96 weeks
Outcome Measure
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 96
Outcome Description
Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Outcome Time Frame
Up to 144 weeks
Outcome Measure
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 144
Outcome Description
Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48
Outcome Description
Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96
Outcome Description
Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Outcome Time Frame
Baseline; Week 144
Outcome Measure
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 144
Outcome Description
Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Outcome Time Frame
Baseline; Week 48
Outcome Measure
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48
Outcome Description
Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Outcome Time Frame
Baseline; Week 96
Outcome Measure
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96
Outcome Description
Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Outcome Time Frame
Baseline; Week 144
Outcome Measure
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 144
Start Date
Start Date Type
Actual
Status Verified Date
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