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; Drug: E/C/F/TAF; 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

Study Timeline

• Study First Submitted: 2013-02-20
• Study First Submitted QC: 2013-02-20
• Study First Posted: 2013-02-22
• Study Start: 2013-03-12
• Primary Completion: 2014-09-19
• Disposition First Submitted: 2015-07-28
• Disposition First Submitted QC: 2015-07-28
• Disposition First Posted: 2015-08-18
• Results First Submitted: 2015-12-04
• Results First Submitted QC: 2015-12-04
• Results First Posted: 2016-01-08
• Study Completion: 2018-10-03
• Status Verified: 2019-10
• Last Update Submitted: 2020-02-18
• Last Update Posted: 2020-03-02

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

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

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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