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

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: HIV Infections; Acquired Immunodeficiency Syndrome

Treatments: Drug: E/C/F/TDF Placebo; Drug: ATV Placebo; Drug: RTV Placebo; Drug: ATV; Drug: E/C/F/TDF; Drug: FTC/TDF Placebo; Drug: FTC/TDF; Drug: RTV; Drug: E/C/F/TAF

Study type: Interventional

Funder types: Industry

Identifiers

NCT01705574

GS-US-236-0128

2012-003708-11 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 583 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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583 participants in 3 patient groups

E/C/F/TDF

Experimental group

Description:

E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo

Treatment:

Drug: RTV Placebo

Drug: E/C/F/TDF

Drug: ATV Placebo

Drug: FTC/TDF Placebo

ATV + RTV+ FTC/TDF

Active Comparator group

Description:

ATV + RTV + FTC/TDF + E/C/F/TDF placebo

Treatment:

Drug: RTV

Drug: FTC/TDF

Drug: ATV

Drug: E/C/F/TDF Placebo

Open-Label Extension Phase

Experimental group

Description:

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.

Treatment:

Drug: E/C/F/TAF

Drug: RTV

Drug: FTC/TDF

Drug: E/C/F/TDF

Drug: ATV