Clinical trial NCT01495702: Study to Evaluate Switching From Regimens Consisting of a Nonnucleoside Reverse Transcriptase Inhibitor Plus Emtricitabine and Tenofovir DF 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 Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) Plus Emtricitabine (FTC) and Tenofovir DF (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: 2011-12-20
Enrollment: 439
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 noninferiority of Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus Truvada® (FTC/TDF) 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 stable on the current formulation(s) of an antiretroviral regimen consisting of an NNRTI plus FTC/TDF for ≥ 6 consecutive months preceding the screening visit. This includes those who began a regimen with individual drug components and subsequently simplified to include a fixed-dose combination formulation of the same drugs.
* Be on the first or second antiretroviral regimen with 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
* Adequate hematologic function
* Serum amylase ≤ 5 × ULN
* Estimated glomerular filtration rate ≥ 70 mL/min
* Females of childbearing potential must agree to utilize protocol recommended contraception methods or be nonheterosexually active, practice sexual abstinence from screening throughout the duration of the study period and for 12 weeks for participants on EFV/FTC/TDF or efavirenz or 30 days for the rest of participants 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 protocol-recommended methods of contraception during heterosexual intercourse or be nonheterosexually active, and practice sexual abstinence from the screening visit.
* Age ≥ 18 years

Exclusion Criteria:

* 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 those 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 (KS), basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma. Persons with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of baseline and must not be anticipated to require systemic therapy during the study.
* Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
* 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: Beverly Hills
country: United States
facility: AHF Research Center
state: California
city: Beverly Hills
country: United States
facility: Pacific Oak Medical Group
state: California
city: Hayward
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, 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: Oakland
country: United States
facility: Alameda County Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group
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
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, P.C.
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond MD, PA, Inc
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research
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: ValuHealth MD, LLC
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates of Northwest Florida
state: Florida
city: Safety Harbor
country: United States
facility: Health Positive
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID Group, PC
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: HIV Program 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: ID Care
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: New York
country: United States
facility: Aaron Diamond AIDS Research Center
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: Philadelphia FIGHT
state: Pennsylvania
city: Dallas
country: United States
facility: Southwest Infectious Disease Clinical Researach 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 E. Crofoot MD, PA
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education - Infectious Disease
state: Virginia
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
city: South Yarra
country: Australia
facility: Prahran Market Clinic
city: Sydney
country: Australia
facility: East Sydney Doctors
city: Wien
country: Austria
facility: Medical University of Vienna
city: Wien
country: Austria
facility: Otto Wagner Spital
city: Antwerpen
country: Belgium
facility: SEAMEO Regional Centre for Tropical Medicine
city: Bruxelles
country: Belgium
facility: Hôpitaux IRIS Sud
city: Leuven
country: Belgium
facility: University Hospital of Leuven
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Medical Clinic
state: Ontario
city: Montreal
country: Canada
facility: Clinique Medicale Du Quartier Latin
state: Quebec
city: Besancon
country: France
facility: CHU de Besancon - Hopital Saint-Jacques
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Paris
country: France
facility: Hopital Saint Antoine
city: Berlin
country: Germany
facility: EPIMED GmbH
city: Berlin
country: Germany
facility: MIB Dienstleistung GmbH
city: Bonn
country: Germany
facility: Medizinische Universitätsklinik
city: Frankfurt
country: Germany
facility: Infektiologikum
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Hamburg
country: Germany
facility: ICH Study Center
city: München
country: Germany
facility: MUC Research GmbH
city: Busto Arsizio/Varese
country: Italy
facility: Azienda Ospedaliera Ospedale di Circolo Busto Arsizio
city: Milano
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Roma
country: Italy
facility: Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria - CHLN EPE
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico Inc
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Cataluña
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
state: Galicia
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Valencia
country: Spain
facility: Hospital La Fe de Valencia
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: Homerton University Hospital
city: London
country: United Kingdom
facility: South London Healthcare NHS Trust
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: London
country: United Kingdom
facility: Chelsea & Westminster Hospital
Study officials:
affiliation: Gilead Sciences
name: Damian McColl
role: STUDY_DIRECTOR
References:
citation: Pozniak A, Flamm J, Antinori A, Bloch M, Ward D, Berenguer J, Cote P, Andreatta K, Garner W, Szwarcberg J, Nguyen-Cleary T, McColl DJ, Piontkowsky D. Switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir DF from non-nucleoside reverse transcriptase inhibitor plus coformulated emtricitabine and tenofovir DF regimens: Week 96 results of STRATEGY-NNRTI. HIV Clin Trials. 2017 Jul;18(4):141-148. doi: 10.1080/15284336.2017.1338844. Epub 2017 Jul 9.
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.