Clinical trial NCT01818596: Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
HIV Infections
Keywords: HIV
HIV-1 Infected
Treatment Experienced
Treatment Naive
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-03-26
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy
timeFrame: Baseline; Week 2, 4, or 8; Week 24
measure: Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48
timeFrame: Baseline; Weeks 24 and 48
measure: Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48
timeFrame: Baseline; Weeks 24 and 48
measure: Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
timeFrame: Baseline; Weeks 24, 48, 96, and 144
measure: Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
timeFrame: Baseline; Weeks 24, 48, 96, and 144
measure: Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities
timeFrame: Baseline up to Week 240 plus 30 days
measure: Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144
timeFrame: Weeks 24, 48, 96, and 144
measure: Pharmacokinetic (PK) Parameter: Cmax of TAF
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: PK Parameter: Tmax of TAF
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: PK Parameter: Clast of TAF
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: PK Parameter: Tlast of TAF
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: PK Parameter: λz of TAF
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: PK Parameter: AUCtau of TAF
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: PK Parameter: t1/2 of TAF
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study
timeFrame: Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
measure: Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144
timeFrame: Baseline; Weeks 48, 96, and 144
measure: Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144
timeFrame: Baseline; Weeks 48, 96, and 144
measure: Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144
timeFrame: Baseline; Weeks 48, 96, and 144
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Maricopa Integrated Health System - McDowell Clinic
state: Arizona
city: Phoenix
country: United States
facility: Pueblo Family Physicians
state: Arizona
city: Little Rock
country: United States
facility: Health for Life Clinic PLLC
state: Arkansas
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Hayward
country: United States
facility: Kaiser Permanente
state: California
city: Long Beach
country: United States
facility: Long Beach Education and Research Consultants
state: California
city: Los Angeles
country: United States
facility: LA Gay & Lesbian Center - Jeffrey Goodman Special Care Clinic
state: California
city: Los Angeles
country: United States
facility: Peter J Ruane, MD, Inc
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD, Inc
state: California
city: Palm Springs
country: United States
facility: Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente CTU San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Washington
country: United States
facility: Dupont Circle Physician's Group
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond, MD PA
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Orlando
country: United States
facility: Idocf/Valuhealthmd
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Wilton Manors
country: United States
facility: Rowan Tree Medical, P.A.
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center, P.C.
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Kansas City
country: United States
facility: The Kansas City Care Clinic (KC Free Health Clinic)
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Albany
country: United States
facility: Upstate Infectious Diseases Associates
state: New York
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital/Division of Infectious Diseases
state: New York
city: Rochester
country: United States
facility: Aids Care
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of PA HIV Clinical Trials Unit
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Bellaire
country: United States
facility: St. Hope Foundation
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, PA
state: Texas
city: Harlingen
country: United States
facility: Garcias' Family Health Group
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD, PA
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Melbourne
country: Australia
facility: Clinical Research Infectious Diseases Department- Alfred Hospital
state: Victoria
city: Prahran
country: Australia
facility: Prahran Market Clinic
state: Victoria
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudios Virologicos (IDEV)
city: Lyon
country: France
facility: Hopital de la Croix Rousse
city: Paris
country: France
facility: GHPS Service des maladies infectieuses et tropicales pavillon Laveran unité de recherche clinique
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Dr. Juan I. Menchaca
state: Jalisco
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Germans Trias i Pujol University Hospital
city: Madrid
country: Spain
facility: Hospital La Paz
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross AIDS Research Centre
city: Bangkok
country: Thailand
facility: Faculty of Medicine Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital, Khon Kaen University
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Kings College London
city: London
country: United Kingdom
facility: Chelsea and Westminster NHS Foundation Trust Hospital
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS foundation Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Pozniak A, Arribas JR, Gathe J, Gupta SK, Post FA, Bloch M, Avihingsanon A, Crofoot G, Benson P, Lichtenstein K, Ramgopal M, Chetchotisakd P, Custodio JM, Abram ME, Wei X, Cheng A, McCallister S, SenGupta D, Fordyce MW; GS-US-292-0112 Study Team. Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. J Acquir Immune Defic Syndr. 2016 Apr 15;71(5):530-7. doi: 10.1097/QAI.0000000000000908.
citation: Post FA, Tebas P, Clarke A, Cotte L, Short WR, Abram ME, Jiang S, Cheng A, Das M, Fordyce MW. Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):180-184. doi: 10.1097/QAI.0000000000001186.