Study to Evaluate the Safety and Efficacy of E/C/F/TAF Versus E/C/F/TDF in HIV-1 Positive, Antiretroviral Treatment-Naive Adults
- Conditions
- HIVHIV Infections
- Interventions
- Registration Number
- NCT01797445
- Lead Sponsor
- Gilead Sciences
- 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) in HIV-1 positive, antiretroviral treatment-naive adults.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 872
- 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 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
- Age ≥ 18 years
Key
- A new 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
- Receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or participants with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description E/C/F/TAF (Double-Blind) E/C/F/TDF Placebo E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. E/C/F/TDF (Double-Blind) E/C/F/TDF E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. E/C/F/TDF (Double-Blind) E/C/F/TAF Placebo E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. E/C/F/TAF (Double-Blind) E/C/F/TAF E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. Open-Label E/C/F/TAF E/C/F/TAF After the unblinding visit, in countries where E/C/F/TAF is not commercially available, participants (except in UK) who complete 144 weeks of study will be given the option to receive open-label E/C/F/TAF and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 Week 48 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.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Spine BMD at Week 48 Baseline; Week 48 Spine BMD was assessed by DXA scan.
Percent Change From Baseline in Spine BMD at Week 96 Baseline; Week 96 Spine BMD was assessed by DXA scan.
Change From Baseline in Serum Creatinine at Week 96 Baseline; Week 96 Percentage of Participants With Treatment-emergent Proteinuria Through Week 48 Baseline to Week 48 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.
Percentage of Participants With Treatment-emergent Proteinuria Through Week 96 Baseline to Week 96 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.
Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 Baseline; Week 48 Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 Baseline; Week 96 Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48 Baseline; Week 48 Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96 Baseline; Week 96 Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Week 96 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.
Change From Baseline in CD4+ Cell Count at Week 48 Baseline; Week 48 Change From Baseline in CD4+ Cell Count at Week 96 Baseline; Week 96 Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48 and 96 Weeks 48 and 96 The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Weeks 48 and 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.
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 Baseline; Week 48 Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Percent Change From Baseline in Hip BMD at Week 96 Baseline; Week 96 Hip BMD was assessed by DXA scan.
Change From Baseline in Serum Creatinine at Week 48 Baseline; Week 48
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (116)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
Kaiser Permanente - Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
University of Southern California AIDS Clinical Trials Group
🇺🇸Los Angeles, California, United States
Peter J. Ruane, Inc.
🇺🇸Los Angeles, California, United States
Anthony Mills MD Inc
🇺🇸Los Angeles, California, United States
Alameda County Medical Center
🇺🇸Oakland, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of California, Davis Medical Center
🇺🇸Sacramento, California, United States
Kaiser Permanente Medical Group
🇺🇸Sacramento, California, United States
Scroll for more (106 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States