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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01818596
Other study ID # GS-US-292-0112
Secondary ID 2013-000516-25
Status Completed
Phase Phase 3
First received
Last updated
Start date March 27, 2013
Est. completion date July 18, 2018

Study information

Verified date June 2019
Source Gilead Sciences
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 252
Est. completion date July 18, 2018
Est. primary completion date July 31, 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
E/C/F/TAF
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food

Locations

Country Name City State
Australia Holdsworth House Medical Practice Darlinghurst New South Wales
Australia Clinical Research Infectious Diseases Department- Alfred Hospital Melbourne Victoria
Australia Prahran Market Clinic Prahran Victoria
Dominican Republic Instituto Dominicano de Estudios Virologicos (IDEV) Santo Domingo
France Hopital de la Croix Rousse Lyon
France GHPS Service des maladies infectieuses et tropicales pavillon Laveran unité de recherche clinique Paris
Mexico Hospital Civil de Guadalajara Dr. Juan I. Menchaca Guadalajara Jalisco
Netherlands University Medical Center Utrecht Utrecht
Spain Germans Trias i Pujol University Hospital Barcelona
Spain Hospital Universitari de Bellvitge Barcelona
Spain Hospital La Paz Madrid
Thailand Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital Bangkok
Thailand Faculty of Medicine Ramathibodi Hospital, Mahidol University Bangkok
Thailand HIV-NAT, Thai Red Cross AIDS Research Centre Bangkok
Thailand Srinagarind Hospital, Khon Kaen University Khon Kaen
United Kingdom Brighton & Sussex University Hospitals NHS Trust Brighton
United Kingdom Chelsea and Westminster NHS Foundation Trust Hospital London
United Kingdom Kings College London London
United Kingdom Central Manchester University Hospitals NHS foundation Trust Manchester
United States Albany Medical College Albany New York
United States Upstate Infectious Diseases Associates Albany New York
United States University of Colorado Aurora Colorado
United States St. Hope Foundation Bellaire Texas
United States Be Well Medical Center, P.C. Berkley Michigan
United States Pacific Oaks Medical Group Beverly Hills California
United States Community Research Initiative of New England Boston Massachusetts
United States Jacobi Medical Center Bronx New York
United States Montefiore Medical Center Bronx New York
United States University of Cincinnati Cincinnati Ohio
United States MetroHealth Medical Center Cleveland Ohio
United States North Texas Infectious Diseases Consultants, PA Dallas Texas
United States Infectious Disease Specialists of Atlanta Decatur Georgia
United States National Jewish Health Denver Colorado
United States Henry Ford Health System Detroit Michigan
United States Gary J. Richmond, MD PA Fort Lauderdale Florida
United States Midway Immunology and Research Center Fort Pierce Florida
United States Garcias' Family Health Group Harlingen Texas
United States Kaiser Permanente Hayward California
United States Gordon E. Crofoot MD, PA Houston Texas
United States Therapeutic Concepts, PA Houston Texas
United States Indiana University School of Medicine Indianapolis Indiana
United States The Kansas City Care Clinic (KC Free Health Clinic) Kansas City Missouri
United States Health for Life Clinic PLLC Little Rock Arkansas
United States Long Beach Education and Research Consultants Long Beach California
United States Anthony Mills MD, Inc Los Angeles California
United States LA Gay & Lesbian Center - Jeffrey Goodman Special Care Clinic Los Angeles California
United States Peter J Ruane, MD, Inc Los Angeles California
United States Mercer University Macon Georgia
United States North Shore University Hospital/Division of Infectious Diseases Manhasset New York
United States Hennepin County Medical Center Minneapolis Minnesota
United States Jersey Shore University Medical Center Neptune New Jersey
United States Saint Michael's Medical Center Newark New Jersey
United States Idocf/Valuhealthmd Orlando Florida
United States Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group Palm Springs California
United States Thomas Jefferson University Philadelphia Pennsylvania
United States University of PA HIV Clinical Trials Unit Philadelphia Pennsylvania
United States Maricopa Integrated Health System - McDowell Clinic Phoenix Arizona
United States Pueblo Family Physicians Phoenix Arizona
United States Aids Care Rochester New York
United States Kaiser Permanente Medical Group Sacramento California
United States Southampton Healthcare, Inc. Saint Louis Missouri
United States Kaiser Permanente CTU San Francisco San Francisco California
United States Metropolis Medical San Francisco California
United States Southwest CARE Center Santa Fe New Mexico
United States Peter Shalit, MD Seattle Washington
United States The Research Institute Springfield Massachusetts
United States University of South Florida Tampa Florida
United States Dupont Circle Physician's Group Washington District of Columbia
United States Triple O Research Institute, P.A. West Palm Beach Florida
United States Rowan Tree Medical, P.A. Wilton Manors Florida

Sponsors (1)

Lead Sponsor Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Dominican Republic,  France,  Mexico,  Netherlands,  Spain,  Thailand,  United Kingdom, 

References & Publications (2)

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 — View 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. Switchin — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24 eGFR is a measurement of the kidney's ability to filter blood. Baseline; Week 24
Primary 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 eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex. Baseline; Week 24
Primary Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24 eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex. Baseline; Week 24
Secondary Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy aGFR was directly measured using iohexol plasma clearance (CLiohexol). Baseline; Week 2, 4, or 8; Week 24
Secondary Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48 CTX is a biomarker of bone turnover. Baseline; Weeks 24 and 48
Secondary Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48 P1NP is a biomarker of bone turnover. Baseline; Weeks 24 and 48
Secondary Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) at Weeks 24, 48, 96, and 144 Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury. Baseline; Weeks 24, 48, 96, and 144
Secondary Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (µg/g) at Weeks 24, 48, 96, and 144 Urine beta-2-microglobulin is a renal biomarker which is used to evaluate drug-induced kidney injury. Baseline; Weeks 24, 48, 96, and 144
Secondary Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities Adverse events (AEs) and graded laboratory abnormalities occurring during the E/C/F/TAF treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event. Baseline up to Week 240 plus 30 days
Secondary Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 The percentage of participants achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Weeks 24, 48, 96, and 144
Secondary Pharmacokinetic (PK) Parameter: Cmax of TAF Cmax is defined as the maximum concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary PK Parameter: Tmax of TAF Tmax is defined as the time of Cmax. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary PK Parameter: Clast of TAF Clast is defined as the last observable concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary PK Parameter: Tlast of TAF Tlast is defined as the time of Clast. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary PK Parameter: ?z of TAF ?z is defined as the terminal elimination rate constant. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary PK Parameter: AUCtau of TAF AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary PK Parameter: t1/2 of TAF t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study TFV-DP is an active phosphorylated metabolite of tenofovir alafenamide. AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit. Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Secondary Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144 eGFR is a measurement of the kidney's ability to filter blood. Baseline; Weeks 48, 96, and 144
Secondary Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144 eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex. Baseline; Weeks 48, 96, and 144
Secondary Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144 eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex. Baseline; Weeks 48, 96, and 144
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