This trial is active, not recruiting.

Conditions hiv, hiv infections
Treatment e/c/f/taf
Phase phase 3
Sponsor Gilead Sciences
Start date March 2013
End date July 2014
Trial size 245 participants
Trial identifier NCT01818596, 2013-000516-25, GS-US-292-0112


This open-label, multicenter, multi-cohort study is to assess the safety, tolerability, and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) in treatment-naive and treatment-experienced HIV-positive, adult participants with mild to moderate renal impairment.

The primary objective of this study is to evaluate the effect of E/C/F/TAF STR on renal parameters at Week 24. The proportion of subjects achieving virologic response of HIV-1 RNA < 50 copies/mL will also be assessed.

At sites able to conduct the appropriate testing, approximately 30 participants will be enrolled into an intensive pharmacokinetic/pharmacodynamic (PK/PD) substudy to evaluate the PK/PD parameters of the individual components of E/C/F/TAF as well as tenofovir diphosphate (TFV-DP).

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Participants will receive E/C/F/TAF for 96 weeks.
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regimen (STR) administered orally once daily with food

Primary Outcomes

Change from baseline in the estimated glomerular filtration rate (eGFR) at Week 24
time frame: Baseline to Week 24

Secondary Outcomes

Change from baseline in the eGFR at Week 48 and 96
time frame: Baseline to Weeks 48 and 96
Plasma PD (true GFR) of E/C/F/TAF for participants enrolled in the PK/PD sub-study
time frame: Weeks 2, 4, 8, and 24
Change from baseline in bone and renal biomarkers at Weeks 24, 48, and 96
time frame: Weeks 24, 48, and 96
Incidence of adverse events and graded laboratory abnormalities
time frame: Baseline to Week 96
Proportion of participants achieving virologic response at Weeks 24, 48, and 96
time frame: Weeks 24, 48, and 96
Plasma PK of E/C/F/TAF including Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and t1/2 for participants enrolled in the PK/PD sub-study
time frame: Weeks 2, 4, and 8
TFV-DP concentration in peripheral blood mononuclear cell (PBMC) for participants enrolled in PK/PD sub-study
time frame: Weeks 2, 4, and 8

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Cohort 1 (Treatment-experienced Switch) - Must not have a history of known resistance to elvitegravir (EVG), tenofovir disoproxil fumarate (TDF), or emtricitabine (FTC) - Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels (according to the local assay being used) in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening - Estimated GFR 30-69 mL/min according to the Cockcroft-Gault formula for creatinine clearance, using actual weight - May be currently enrolled in Gilead studies GS-US-236-0102, GS-US-236-0103, and GS-US-216-0114, but will be eligible to enroll only after the Week 144 visit is complete, or currently receiving Stribild® (STB) or atazanavir (ATV)/cobicistat (COBI) + Truvada (TVD) in Gilead studies GS-US-236-0104 or GS-US-216-0105, but will be eligible to enroll only after the Week 48 visit is complete. Cohort 2 (Treatment-naïve) - Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening - Screening genotype report provided by Gilead Sciences must show sensitivity to EVG, FTC, and TDF - No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for PrEP (pre-exposure prophylaxis), or PEP (post-exposure prophylaxis), up to 6 months prior to screening - Estimated GFR 30-69 mL/min according to the Cockcroft Gault formula for creatinine clearance, using actual weight All Cohorts: All subjects must meet all of the following inclusion criteria to be eligible for participation in this study: - The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures - CD4+ count of ≥ 50 cells/μL - Stable renal function: serum creatinine measurements to be taken at least once (within three months of screening). - Cause of underlying chronic kidney disease (eg hypertension, diabetes) stable, without change in medical management, for 3 months prior to baseline - Normal electrocardiogram (ECG) - 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 - Females of childbearing potential must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence) from screening throughout the duration of study treatment and for 30 days following the last dose of study drug - Female subjects 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 - Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product. A highly effective method of contraception is defined as two separate forms of contraception, one of which must be an effective barrier method, or male subjects must be non-heterosexually active, or practice sexual abstinence - Age ≥ 18 years Exclusion Criteria: - A new AIDS defining condition (excluding CD4 cell count and percentage criteria) diagnosed within the 30 days prior to screening,with the exception of the first two bullet points - Hepatitis C virus (HCV) antibody positive. Subjects who are HCV positive, but have a documented negative HCV RNA, are eligible. - Hepatitis B surface antigen (HBVsAg) positive - Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study - Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.) - 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 subject study compliance - A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, 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 - Subjects on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone, and dexamethasone) - Subjects receiving ongoing therapy with any medications not to be used with EVG, COBI, FTC, or TAF or subjects with any known allergies to the excipients of E/C/F/TAF STR

Additional Information

Official title A Phase 3 Open-label Safety Study of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1 Positive Patients With Mild to Moderate Renal Impairment
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Gilead Sciences.