Safety and Efficacy of E/C/F/TDF Versus RTV-Boosted ATV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment-Naive Women

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to evaluate the efficacy of a regimen containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) versus ritonavir (RTV)-boosted atazanavir (ATV/r) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in HIV-1 infected, antiretroviral treatment-naive adult women.

Official Title
-----------------
A Randomized, Double-blind Phase 3B Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Women

Conditions
-----------------
Acquired Immunodeficiency Syndrome, HIV Infections

Intervention / Treatment
-----------------
* Drug: E/C/F/TDF
* Drug: ATV
* Drug: RTV
* Drug: FTC/TDF
* Drug: E/C/F/TDF Placebo
* Drug: ATV Placebo
* Drug: RTV Placebo
* Drug: FTC/TDF Placebo
* Drug: E/C/F/TAF


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Female (at birth), age ≥ 18 years Ability to understand and sign a written informed consent form Plasma HIV-1 RNA levels ≥ 500 copies/mL No prior use of any approved or investigational antiretroviral drug for any length of time Screening genotype report must show sensitivity to emtricitabine (FTC), tenofovir disoproxil fumarate (TDF) and atazanavir (ATV) boosted with ritonavir (RTV) Normal ECG Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula Hepatic transaminases ≤ 5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dL Adequate hematologic function Serum amylase ≤ 5 x ULN Women of childbearing potential must agree to utilize protocol recommended contraception methods or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug Women 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. Key Exclusion Criteria: A new AIDS defining condition diagnosed within the 30 days Females receiving drug treatment for Hepatitis C, or females who are anticipated to receive treatment for Hepatitis C during the course of the study Females experiencing decompensated cirrhosis Females who are breastfeeding Positive serum pregnancy test (female of childbearing potential) Have an implanted defibrillator or pacemaker Have an ECG pulse rate interval ≥ 220 msec Current alcohol or substance use which may potentially interfere with the female's study compliance 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 requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline Participation in any other clinical trial without prior approval Any other clinical condition or prior therapy that would make the female unsuitable for the study or unable to comply with the dosing requirements Females receiving ongoing therapy with any disallowed medications, including drugs not to be used with elvitegravir, cobicistat, FTC, TDF, ATV, RTV; or females with any known allergies to the excipients of Stribild® tablets, Truvada® tablets, atazanavir capsules or ritonavir tablets Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E/C/F/TDF<br>E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo | Drug: E/C/F/TDF<br>* 150/150/200/300 mg FDC tablet administered orally with food once daily<br>* Other names: Stribild®;Drug: ATV Placebo<br>* Tablet administered orally with food once daily<br>Drug: RTV Placebo<br>* Capsule administered orally with food once daily<br>Drug: FTC/TDF Placebo<br>* Tablet administered orally with food once daily<br>|
| Active Comparator: ATV + RTV+ FTC/TDF<br>ATV + RTV + FTC/TDF + E/C/F/TDF placebo | Drug: ATV<br>* 300 mg capsule administered orally with food once daily<br>* Other names: Reyataz®;Drug: RTV<br>* 100 mg tablet administered orally with food once daily<br>* Other names: Norvir®;Drug: FTC/TDF<br>* 200/300 mg tablet administered orally with food once daily<br>* Other names: Truvada®;Drug: E/C/F/TDF Placebo<br>* Tablet administered orally with food once daily<br>|
| Experimental: Open-Label Extension Phase<br>After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF. | Drug: E/C/F/TDF<br>* 150/150/200/300 mg FDC tablet administered orally with food once daily<br>* Other names: Stribild®;Drug: ATV<br>* 300 mg capsule administered orally with food once daily<br>* Other names: Reyataz®;Drug: RTV<br>* 100 mg tablet administered orally with food once daily<br>* Other names: Norvir®;Drug: FTC/TDF<br>* 200/300 mg tablet administered orally with food once daily<br>* Other names: Truvada®;Drug: E/C/F/TAF<br>* 150/150/200/10 mg FDC tablet administered orally with food once daily<br>* Other names: Genvoya®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase as Determined by the US FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 of the double-blind phase was analyzed using the snapshot algorithm, which defines a participant'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 |
| --- | --- | --- |
| Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase |  | Baseline; Week 48 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 for the STB Group as Determined by the US FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant'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 96 | 
| Percentage of Participants Receiving STB or ATV+RTV+TVD With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open-Label Extension Phase | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 of the open-label phase was analyzed using the snapshot algorithm, which defines a participant'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. | Open-Label Extension Week 48 | 
| Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase |  | Baseline; Open-Label Extension Week 48 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Treatment-Naive, Women, WAVES, HIV-1