This open label trial will recruit participants with HIV who have mild to moderate kidney function problems. Participants will receive an investigational single tablet regimen (E/C/F/TAF). This combination tablet contains the experimental drug TAF.

Phase 1

Conditions: Human Immunodeficiency Virus (HIV-1) Infection
MedDRA version: 16.0Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2013-000516-25-BE

Lead Sponsor: Gilead Sciences Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 150

Inclusion Criteria

Cohort 1 (Treatment-experienced Switch)
• Must not have a history of known resistance to EVG, TDF or FTC
• Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels 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
• May be currently enrolled in Gilead studies GS-US-236-0103 and
GS-US-216-0114, but will be eligible to enroll only after the Week 144 visit is complete

Cohort 2 (Treatment-naïve)
• Plasma HIV-1 RNA levels = 1,000 copies/mL at screening
• Screening genotype report 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

All Cohorts:
• 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
• Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
• 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
• 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 or have a vasectomized partner) 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 abstinenc
• Age = 18 years

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

• A new AIDS-defining condition
• HCV antibody positive
• Hepatitis B surface antigen 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
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• 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 (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Subjects with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline and must not be anticipated to require systemic therapy during the study
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy
• Subjects on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases
• Subjects receiving ongoing therapy with any of the disallowed medications in the protocol, including drugs 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
• 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) on renal parameters<br>at Week 24;Secondary Objective: • To evaluate the effect of the E/C/F/TAF STR on renal parameters at Weeks 48 and 96<br>• To measure the proportion of subjects achieving virologic response (HIV-1 RNA < 50 copies/mL, FDA snapshot analysis) at Weeks 24, 48, and 96<br>• To evaluate the safety and tolerability of the E/C/F/TAF STR through 96 weeks of treatment;Primary end point(s): The primary endpoint is the change from baseline at Week 24 in the following:<br>1) Estimated glomerular filtration rate (eGFR) calculated by Cockcroft-Gault (CG) formula<br>2) eGFR by CKD-EPI formula based on Cystatin C (mg/L) and adjusted for age and sex<br>3) eGFR by CKD-EPI formula based on serum creatinine and adjusted for age, sex, and race;Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Weeks 24, 48 and 96;Secondary end point(s): The secondary endpoints are as follows:<br>1) Change from baseline at Week 48 and 96 in eGFR estimated by <br>a) CG formula based on serum creatinine, <br>b) CKD-EPI formula based on cystain C and adjusted for age and sex,<br>c) CKD-EPI formula based on serum creatinine and adjusted for age, sex, and race.<br>2) True GFR directly measured using iohexol plasma clearance for subjects enrolled in the PK/PD sub-study<br>3) Change from baseline in bone biomarkers and renal biomarkers at Weeks 24, 48, and 96.<br>4) Incidence of adverse events and graded laboratory abnormalities.<br>5) The proportion of subjects achieving virologic response at Weeks 24, 48, and 96 <br>6) PK parameters: Cmax, Tmax, Clast, Tlast, Ctau, ?z, AUCtau, and T½, for subjects enrolled in the PK/PD sub-study.<br>7) Tenofovir diphosphate (TFV-DP) concentration in peripheral blood mononuclear cell (PBMC) for subjects enrolled in PK/PD sub-study.<br><br>

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