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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV, HIV Infections

Intervention / Treatment
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* Drug: E/C/F/TAF
* Drug: E/C/F/TDF
* Drug: E/C/F/TDF Placebo
* Drug: E/C/F/TAF Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E/C/F/TAF (Double-Blind Phase)<br>E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks | Drug: E/C/F/TAF<br>* 150/150/200/10 mg FDC tablet administered orally once daily<br>* Other names: Genvoya®;Drug: E/C/F/TDF Placebo<br>* Tablet administered orally once daily<br>|
| Active Comparator: E/C/F/TDF (Double-Blind Phase)<br>E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks | Drug: E/C/F/TDF<br>* 150/150/200/300 mg FDC tablet administered orally once daily<br>* Other names: Stribild®;Drug: E/C/F/TAF Placebo<br>* Tablet administered orally once daily<br>|
| Experimental: Open-Label Extension Phase<br>After study unblinding, participants who complete 144 weeks of the study had the option to receive open-label E/C/F/TAF until commercially available, or until Gilead Sciences terminated the study in that country. | Drug: E/C/F/TAF<br>* 150/150/200/10 mg FDC tablet administered orally once daily<br>* Other names: Genvoya®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 and 144 | 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. | Weeks 96 and 144 | 
| Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48, 96, and 144 | 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. | Weeks 48, 96. and 144 | 
| 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 | 
| Change From Baseline in CD4+ Cell Count at Week 144 |  | Baseline; Week 144 | 
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan. | Baseline; Week 48 | 
| Percent Change From Baseline in Hip BMD at Week 96 | Hip BMD was assessed by DXA scan. | Baseline; Week 96 | 
| Percent Change From Baseline in Hip BMD at Week 144 | Hip BMD was assessed by DXA scan. | Baseline; Week 144 | 
| Percent Change From Baseline in Spine BMD at Week 48 | Spine BMD was assessed by DXA scan. | Baseline; Week 48 | 
| Percent Change From Baseline in Spine BMD at Week 96 | Spine BMD was assessed by DXA scan. | Baseline; Week 96 | 
| Percent Change From Baseline in Spine BMD at Week 144 | Spine BMD was assessed by DXA scan. | Baseline; Week 144 | 
| Change From Baseline in Serum Creatinine at Week 48 |  | Baseline; Week 48 | 
| Change From Baseline in Serum Creatinine at Week 96 |  | Baseline; Week 96 | 
| Change From Baseline in Serum Creatinine at Week 144 |  | Baseline; Week 144 | 
| Percentage of Participants Experiencing Treatment-emergent Proteinuria Through 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. | Up to 48 weeks | 
| Percentage of Participants Experiencing Treatment-emergent Proteinuria Through 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. | Up to 96 weeks | 
| Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 144 | 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. | Up to 144 weeks | 
| Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 | Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 48 | 
| Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 | Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 96 | 
| Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 144 | Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 144 | 
| Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48 | Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 48 | 
| Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96 | Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 96 | 
| Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 144 | Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury. | Baseline; Week 144 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Treatment Naive, HIV 1 Infected, Female, Women