Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI [GS-9350])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir-boosted atazanavir (ATV/r) plus the standard of care nucleoside reverse transcriptase inhibitor (NRTI) backbone FTC/TDF (Truvada®). ATV/r + FTC/TDF was selected as the active comparator for this study as it is a preferred protease inhibitor-based regimen in guidelines for the treatment of HIV-1 infected, 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/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Conditions
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HIV, HIV Infections

Intervention / Treatment
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* Drug: Stribild
* Drug: ATV
* Drug: Ritonavir
* Drug: FTC/TDF
* Drug: Stribild Placebo
* Drug: ATV Placebo
* Drug: RTV Placebo
* Drug: FTC/TDF Placebo


Participation Criteria
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Eligibility Criteria
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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 ≥ 5,000 copies/mL at screening No prior use of any approved or investigational antiretroviral drug for any length of time Screening genotype report must show sensitivity to FTC, TDF, and ATV Normal electrocardiogram (ECG) Adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula) Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x the upper limit of the normal range (ULN) Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin Adequate hematologic function Serum amylase ≤ 5 x ULN Males and Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug Age ≥ 18 years Life expectancy ≥ 1 year Exclusion Criteria: A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening Receiving drug treatment for hepatitis C, or anticipated to receive treatment for hepatitis C Subjects experiencing decompensated cirrhosis Females who are breastfeeding Positive serum pregnancy test (female of childbearing potential) Implanted defibrillator or pacemaker Current alcohol or substance use judged by the Investigator to potentially interfere with subject 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 Medications contraindicated for use with EVG, COBI, FTC, TDF, ATV, or ritonavir or subjects with any known allergies to the excipients of Stribild tablets, Truvada tablets, ATV capsules or ritonavir tablets Participation in any other clinical trial without prior approval Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stribild<br> | Drug: Stribild<br>* Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR administered orally once daily<br>Drug: ATV Placebo<br>* Placebo to match ATV administered orally once daily<br>Drug: RTV Placebo<br>* Placebo to match RTV administered orally once daily<br>Drug: FTC/TDF Placebo<br>* Placebo to match FTC/TDF administered orally once daily<br>|
| Active Comparator: ATV/r + FTC/TDF<br> | Drug: ATV<br>* Atazanavir 300 mg capsule administered orally once daily<br>Drug: Ritonavir<br>* Ritonavir (RTV; /r) 100 mg tablet administered orally once daily<br>* Other names: Norvir®;Drug: FTC/TDF<br>* FTC/TDF 200/300 mg tablet administered orally once daily<br>* Other names: Truvada;Drug: Stribild Placebo<br>* Placebo to match Stribild administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48 |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96 |  | Week 96 | 
| The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144 |  | Week 144 | 
| The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192 |  | Week 192 | 
| The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm |  | Week 48 | 
| The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192 | Change = value of the relevant time point minus the baseline value | Baseline; Weeks 48, 96, 144, and 192 | 
| The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 |  | Week 48 | 

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