Safety and Efficacy of COBI-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and efficacy of a regimen containing cobicistat-boosted atazanavir (ATV+COBI) plus emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) fixed-dose combination (FDC) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF FDC in HIV-1 infected, antiretroviral treatment-naive adults. Participants will be randomized in a 1:1 ratio. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.

Official Title
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A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9350-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With 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: COBI
* Drug: RTV
* Drug: ATV
* Drug: FTC/TDF
* Drug: COBI placebo
* Drug: RTV 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 ECG Adequate renal function (eGFR calculated using the Cockcroft-Gault equation ≥ 70 mL/min) Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (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 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) Have an implanted defibrillator or pacemaker Have an ECG PR interval ≥ 220 msec Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance. A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive 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 COBI, emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), atazanavir (ATV), ritonavir (RTV) or subjects with any known allergies to the excipients of COBI tablets, Truvada tablets, atazanavir capsules or ritonavir tablets. Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial. 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATV+COBI+FTC/TDF<br>COBI + RTV placebo + ATV + FTC/TDF once daily | Drug: COBI<br>* Cobicistat (COBI) 150 mg tablet administered orally once daily<br>* Other names: GS-9350;Drug: ATV<br>* Atazanavir (ATV) 300 mg capsule administered orally once daily<br>* Other names: Reyataz®;Drug: FTC/TDF<br>* Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily<br>* Other names: Truvada®;Drug: RTV placebo<br>* Placebo to match RTV administered orally once daily<br>|
| Active Comparator: ATV+RTV+FTC/TDF<br>RTV + COBI placebo + ATV + FTC/TDF once daily | Drug: RTV<br>* Ritonavir (RTV) 100 mg tablet administered orally once daily<br>* Other names: Norvir®;Drug: ATV<br>* Atazanavir (ATV) 300 mg capsule administered orally once daily<br>* Other names: Reyataz®;Drug: FTC/TDF<br>* Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily<br>* Other names: Truvada®;Drug: COBI placebo<br>* Placebo to match COBI administered orally once daily<br>|

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 with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the prespecified 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 Week 96 | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm. | Week 96 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 144 was analyzed using the snapshot algorithm. | Week 144 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192 | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 192 was analyzed using the snapshot algorithm. | Week 192 | 
| Change From Baseline in CD4 Cell Count at Week 48 |  | Baseline to Week 48 | 
| Change From Baseline in CD4 Cell Count at Week 96 |  | Baseline to Week 96 | 
| Change From Baseline in CD4 Cell Count at Week 144 |  | Baseline to Week 144 | 
| Change From Baseline in CD4 Cell Count at Week 192 |  | Baseline to Week 192 | 

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