Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment
Condition: HIV; HIV Infections
MeSH terms: HIV Infections; Renal Insufficiency
Intervention: E/C/F/TAF
Intervention description: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food
Intervention MeSH terms: Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 252.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; HIV-1 Infected; Treatment Experienced; Treatment Naive

Summary:

      The primary objective of this study is to evaluate the effect of
      elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose
      combination (FDC) tablet on renal parameters at Week 24 in treatment-naive and
      treatment-experienced HIV-positive, adults with mild to moderate renal impairment.
    

Eligibility criteria:

        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 individuals 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

          -  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

          -  Males 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 males must be non-heterosexually active, or practice
             sexual abstinence

        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. Individuals who are HCV positive, but have
             a documented negative HCV RNA, are eligible

          -  Hepatitis B surface antigen (HBVsAg) positive

          -  Individuals receiving drug treatment for Hepatitis C, or individuals who are
             anticipated to receive treatment for Hepatitis C during the course of the study

          -  Individuals 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 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

          -  Individuals on hemodialysis, other forms of renal replacement therapy, or on treatment
             for underlying kidney diseases (including prednisolone and dexamethasone)

          -  Individuals receiving ongoing therapy with any medications not to be used with EVG,
             COBI, FTC, or TAF or individuals with any known allergies to the excipients of
             E/C/F/TAF

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.