Study to Evaluate the Safety and Efficacy of E/C/F/TAF Versus E/C/F/TDF in HIV-1 Positive, Antiretroviral Treatment-Naive Adults

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: HIV; HIV Infections

Treatments: Drug: E/C/F/TDF; Drug: E/C/F/TDF Placebo; Drug: E/C/F/TAF; Drug: E/C/F/TAF Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01797445

GS-US-292-0111

2013-000102-37 (EudraCT Number)

Details and patient eligibility

About

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) in HIV-1 positive, antiretroviral treatment-naive adults.

Enrollment: 872 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 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
• Age ≥ 18 years

Key Exclusion Criteria:

• A new 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
• Receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or participants with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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872 participants in 3 patient groups

E/C/F/TAF (Double-Blind)

Experimental group

Description:

E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded.

Treatment:

Drug: E/C/F/TDF Placebo

Drug: E/C/F/TAF

E/C/F/TDF (Double-Blind)

Active Comparator group

Description:

E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded.

Treatment:

Drug: E/C/F/TDF

Drug: E/C/F/TAF Placebo

Open-Label E/C/F/TAF

Experimental group

Description:

After the unblinding visit, in countries where E/C/F/TAF is not commercially available, participants (except in UK) who complete 144 weeks of study will be given the option to receive open-label E/C/F/TAF and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country.

Treatment:

Drug: E/C/F/TAF