Summary

for people ages 18 years and up (full criteria)
at San Diego, California and other locations
study started
estimated completion:

Description

Summary

This open-label, multicenter, multi-cohort study is to assess the safety, tolerability, and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) fixed-dose combination (FDC) tablet 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 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).

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

Keywords

HIV HIV Infections HIV-1 Infected Treatment Experienced Treatment Naive Renal Insufficiency E/C/F/TAF

Eligibility

For people ages 18 years and up

Key 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 glomerular filtration rate (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 for that study 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 for that study is complete.

Cohort 2 (treatment-naive)

  • 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 pre-exposure prophylaxis (PrEP), or post-exposure prophylaxis(PEP), 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

Key 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 (eg, 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

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

Locations

  • University of California San Diego
    San Diego, California, 92103, United States
  • Orange Coast Medical Group
    Newport Beach, California, 92663, United States
  • Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group
    Palm Springs, California, 92262, United States
  • Long Beach Education and Research Consultants
    Long Beach, California, 90813, United States
  • Peter J Ruane, MD, Inc
    Los Angeles, California, 90036, United States
  • Pacific Oaks Medical Group
    Beverly Hills, California, 90211, United States
  • LA Gay & Lesbian Center - Jeffrey Goodman Special Care Clinic
    Los Angeles, California, 90028, United States
  • Anthony Mills MD, Inc
    Los Angeles, California, 90069, United States
  • Pueblo Family Physicians
    Phoenix, Arizona, 85015, United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Gilead Sciences
ID
NCT01818596
Phase
Phase 3
Study Type
Interventional
Last Updated
February 21, 2018