Clinical trial NCT01475838: Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients
Official title: A Phase 3b Randomized, Open-Label Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor (PI + RTV) Plus Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (EVG/COBI/FTC/TDF) in Virologically-Suppressed, HIV-1 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Keywords: HIV-1
HIV
Treatment Experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-11-21
Enrollment: 438
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the non-inferiority of Stribild® (elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a protease inhibitor (PI) boosted with ritonavir (RTV) plus Truvada® (FTC/TDF) fixed-dose combination in maintaining HIV-1 RNA \< 50 copies/mL at Week 48 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of the two regimens through 96 weeks of treatment.


Eligibility criteria: Inclusion Criteria:

* Ability to understand and sign a written informed consent form
* Be on a stable antiretroviral regimen consisting of a ritonavir boosted PI plus FTC/TDF continuously for ≥ 6 consecutive months preceding the screening visit
* Be on the first or second antiretroviral drug regimen documented undetectable plasma HIV 1 RNA levels for ≥ 6 months preceding the screening visit
* No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) for any length of time
* Documented historical genotype prior to starting initial antiretroviral therapy showing no known resistance to TDF or FTC
* HIV RNA \< 50 copies/mL at screening
* Normal ECG
* Hepatic transaminases ≤ 5 × the upper limit of the normal range (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Estimated glomerular filtration rate ≥ 70 mL/min
* Females of childbearing potential must agree to utilize highly effective contraception methods, or be nonheterosexually active, practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug
* Female participants 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 participants must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product, or must be nonheterosexually active, or practice sexual abstinence
* Age ≥ 18 years

Exclusion Criteria:

* A new AIDS-defining condition diagnosed within the 30 days prior to screening
* Females who are breastfeeding
* Positive serum pregnancy test (female of childbearing potential)
* Receiving drug treatment for hepatitis C, or participants who are anticipated to receive treatment for hepatitis C during the course of the study
* Experiencing decompensated cirrhosis
* Have an implanted defibrillator or pacemaker
* Current alcohol or substance abuse that would interfere with compliance
* A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
* Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline, except for intramuscular penicillin for the treatment of syphilis
* Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study
* Receiving ongoing therapy with any of the medications, including drugs not to be used with elvitegravir, cobicistat, FTC, or TDF; or those with any known allergies to the excipients of E/C/F/TDF tablets, or FTC/TDF tablets
* No anticipated need to initiate drugs during the study that are contraindicated
* Receiving other investigational drugs
* Participation in any other clinical trial
* Any other clinical condition or prior therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
timeFrame: Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 96
timeFrame: Baseline; Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Phoenix
country: United States
facility: Pueblo Family Physicians
state: Arizona
city: Beverly Hills
country: United States
facility: AIDS Healthcare Foundation
state: California
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Hayward
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, M.D., Inc.
state: California
city: Los Angeles
country: United States
facility: OASIS Clinic
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD Inc
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: San Francisco
country: United States
facility: Metropolis Medical
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: Washington
country: United States
facility: Dupont Circle Physicians Group, P.C
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates, PC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology & Research Center, LLC
state: Florida
city: Miami
country: United States
facility: The Kinder Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: Idocf/Valuhealthmd, Llc
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates of NW FL, P.A.
state: Florida
city: Safety Harbor
country: United States
facility: AHF Health Positive Tampa Bay
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID Group
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Division of Infectious Diseases
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County/Ruth M. Rothstein CORE Center
state: Illinois
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Kansas City
country: United States
facility: The Kansas City Free Health Clinic
state: Missouri
city: Hillsborough
country: United States
facility: I.D. Care Associates PA
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Mt. Vernon
country: United States
facility: Greiger Clinic
state: New York
city: Charlotte
country: United States
facility: ID Consultants, P.A.
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Dallas
country: United States
facility: Uptown Physicians Group
state: Texas
city: Dallas
country: United States
facility: Southwest Infectious Disease Clinical Research, Inc
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon Crofoot Md, Pa
state: Texas
city: Houston
country: United States
facility: St. Hope Foundation Inc
state: Texas
city: Innsbruck
country: Austria
facility: Innsbruck Medical University
city: Salzburg
country: Austria
facility: Univ.-Kklinik fuer Innere Medizin III
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Wien
country: Austria
facility: Otto-Wagner-Spital
city: Brussels
country: Belgium
facility: UCL Saint Luc
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Liege
country: Belgium
facility: CHU Sart Tilman
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Clinique Medicale Du Quartier Latin
state: Quebec
city: Besançon
country: France
facility: CHU de Besancon, Hopital Saint-Jacques
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Montpellier
country: France
facility: CHU Hôpital Gui de Chauliac
city: Nice
country: France
facility: Archet 1 Chu Nice Department of Infectology
city: Paris Cedex 13
country: France
facility: Maladies Infectieuses Dpt
city: Paris
country: France
facility: Saint-Louis Hospital
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hôpital Bichat-Claude Bernard
city: Paris
country: France
facility: hôpital Tenon
city: Pessac
country: France
facility: Hôpital Haut Lévêque
city: Berlin
country: Germany
facility: Epimed GmbH
city: Bonn
country: Germany
facility: University of Bonn
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Dermatologie, HIV Ambulanz
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe-University Hospital / Infectious Diseases Hs 68
city: Hamburg
country: Germany
facility: ICH Study Center
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Ambulanzzentrum des UKE GmbH, Bereich Infektiologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Koln
country: Germany
facility: Infektlonsambulanz Unlkllnik Koln
city: Munich
country: Germany
facility: Infektionsambulanz, Med Poliklink, Klinikum der Universitat Munchnen
city: Bergamo
country: Italy
facility: Ospedali Riuniti
city: Milano
country: Italy
facility: Fondazione Centro San Raffaele
city: Milano
country: Italy
facility: Clinic of Infectious Diseases, University of Milan-San Paolo Hospital
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Rome
country: Italy
facility: National Institute for Infectious Diseases "L. Spallanzani"
city: Torino
country: Italy
facility: University of Torino, Dept of Infectious Disease
city: Alcabideche
country: Portugal
facility: HHP Hospital de Cascais
city: Lisboa
country: Portugal
facility: Hospital Santo Antonio Dos Capuchos, Centro Hospitalar de Lisboa
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria-CHLN, EPE
city: San Juan
country: Puerto Rico
facility: Clinical Research Puert Rico
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine
city: Alicante
country: Spain
facility: Hospital General Universitario Alicante
city: Barcelona
country: Spain
facility: Hospital clinic
city: Barcelona
country: Spain
facility: Hospital Universitari Bellvitge HIV Unit. Infectious Disease Service.
city: Barcelona
country: Spain
facility: Hospital Germans Trias I Pujol
city: Elche, Alicante
country: Spain
facility: Hospital General Universitario de Elche
city: Madrid
country: Spain
facility: Infectious Diseases Department, Hospital Carlos III
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital La Paz
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Geneva
country: Switzerland
facility: Geneva University Hospital
city: Zurich
country: Switzerland
facility: University Hospital of Zurich; Division of Infectious Diseases and Hospital Epidemiology
city: Zurich
country: Switzerland
facility: Zentrum fur Infektionskrankheiten
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Royal Free Hampstead NHS Trust
city: London
country: United Kingdom
facility: Chelsea and Westminster
Study officials:
affiliation: Gilead Sciences
name: Thai Nguyen-Cleary
role: STUDY_DIRECTOR
References:
citation: Arribas JR, Pialoux G, Gathe J, Di Perri G, Reynes J, Tebas P, Nguyen T, Ebrahimi R, White K, Piontkowsky D. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial. Lancet Infect Dis. 2014 Jul;14(7):581-9. doi: 10.1016/S1473-3099(14)70782-0. Epub 2014 Jun 5.
citation: Pozniak A, Markowitz M, Mills A, Stellbrink HJ, Antela A, Domingo P, Girard PM, Henry K, Nguyen T, Piontkowsky D, Garner W, White K, Guyer B. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infect Dis. 2014 Jul;14(7):590-9. doi: 10.1016/S1473-3099(14)70796-0. Epub 2014 Jun 5.
citation: Arribas JR, DeJesus E, van Lunzen J, Zurawski C, Doroana M, Towner W, Lazzarin A, Nelson M, McColl D, Andreatta K, Swamy R, Szwarcberg J, Nguyen T. Simplification to single-tablet regimen of elvitegravir, cobicistat, emtricitabine, tenofovir DF from multi-tablet ritonavir-boosted protease inhibitor plus coformulated emtricitabine and tenofovir DF regimens: week 96 results of STRATEGY-PI. HIV Clin Trials. 2017 May;18(3):118-125. doi: 10.1080/15284336.2017.1330440. Epub 2017 May 30.
citation: Gathe J, Arribas JR, Van Lunzen J, Garner W, Speck RM, Bender R, Shreay S, Nguyen T. Patient-Reported Symptoms over 48 Weeks in a Randomized, Open-Label, Phase 3b Non-inferiority Trial of Adults with HIV Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir DF Versus Continuation of Ritonavir-Boosted Protease Inhibitor with Emtricitabine and Tenofovir DF. Patient. 2015 Oct;8(5):445-54. doi: 10.1007/s40271-015-0137-9.