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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

Phase 3
Completed
Conditions
HIV
HIV Infections
Interventions
Drug: E/C/F/TDF Placebo
Drug: E/C/F/TAF Placebo
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
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 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

Exclusion Criteria
  • 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
GroupInterventionDescription
E/C/F/TAF (Double-Blind)E/C/F/TDF PlaceboE/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/TDFE/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 PlaceboE/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/TAFE/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/TAFE/C/F/TAFAfter 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
NameTimeMethod
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48Week 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
NameTimeMethod
Percent Change From Baseline in Spine BMD at Week 48Baseline; Week 48

Spine BMD was assessed by DXA scan.

Percent Change From Baseline in Spine BMD at Week 96Baseline; Week 96

Spine BMD was assessed by DXA scan.

Change From Baseline in Serum Creatinine at Week 96Baseline; Week 96
Percentage of Participants With Treatment-emergent Proteinuria Through Week 48Baseline 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 96Baseline 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 48Baseline; 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 96Baseline; 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 48Baseline; 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 96Baseline; 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 96Week 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 48Baseline; Week 48
Change From Baseline in CD4+ Cell Count at Week 96Baseline; Week 96
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48 and 96Weeks 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 48Baseline; Week 48

Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.

Percent Change From Baseline in Hip BMD at Week 96Baseline; Week 96

Hip BMD was assessed by DXA scan.

Change From Baseline in Serum Creatinine at Week 48Baseline; Week 48

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

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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States

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