Clinical trial NCT01106586: Study to Evaluate the Safety and Efficacy of Stribild Versus Ritonavir-Boosted Atazanavir Plus Truvada in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults
Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
HIV Infections
Keywords: HIV 1 Infection
Treatment Naive
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-04-20
Enrollment: 708
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: To evaluate the safety and efficacy of Stribild®, a single tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/cobicistat (COBI \[GS-9350\])/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus ritonavir-boosted atazanavir (ATV/r) plus the standard of care nucleoside reverse transcriptase inhibitor (NRTI) backbone FTC/TDF (Truvada®). ATV/r + FTC/TDF was selected as the active comparator for this study as it is a preferred protease inhibitor-based regimen in guidelines for the treatment of HIV-1 infected, antiretroviral treatment-naive adults.


Eligibility criteria: Inclusion Criteria:

* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at screening
* No prior use of any approved or investigational antiretroviral drug for any length of time
* Screening genotype report must show sensitivity to FTC, TDF, and ATV
* Normal electrocardiogram (ECG)
* Adequate renal function (estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula)
* Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x the upper limit of the normal range (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function
* Serum amylase ≤ 5 x ULN
* Males and Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
* Age ≥ 18 years
* Life expectancy ≥ 1 year

Exclusion Criteria:

* A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening
* Receiving drug treatment for hepatitis C, or anticipated to receive treatment for hepatitis C
* Subjects experiencing decompensated cirrhosis
* Females who are breastfeeding
* Positive serum pregnancy test (female of childbearing potential)
* Implanted defibrillator or pacemaker
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* 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 (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
* Medications contraindicated for use with EVG, COBI, FTC, TDF, ATV, or ritonavir or subjects with any known allergies to the excipients of Stribild tablets, Truvada tablets, ATV capsules or ritonavir tablets
* Participation in any other clinical trial without prior approval
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements

Primary outcomes:
measure: The Percentage of Participants With Virologic Success Using the Food and Drug Administration (FDA)-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 Ribonucleic Acid (RNA) < 50 Copies/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 96
timeFrame: Week 96
measure: The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 144
timeFrame: Week 144
measure: The Percentage of Participants With Virologic Success Using the FDA-Defined Snapshot Analysis as Determined by the Achievement of HIV-1 RNA < 50 Copies/mL at Week 192
timeFrame: Week 192
measure: The Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 Using the FDA-defined Time to Loss of Virologic Response (TLOVR) Algorithm
timeFrame: Week 48
measure: The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192
timeFrame: Baseline; Weeks 48, 96, 144, and 192
measure: The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Little Rock
country: United States
facility: Health for Life Clinic PLLC
state: Arkansas
city: Beverly Hills
country: United States
facility: AHF Research Center
state: California
city: Costa Mesa
country: United States
facility: CSI Clinical Trials, Inc.
state: California
city: Denver
country: United States
facility: Apex Research, LLC
state: California
city: Hayward
country: United States
facility: Kaiser Permanente Hospital
state: California
city: Long Beach
country: United States
facility: Living Hope Clinical Foundation
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Los Angeles
country: United States
facility: Los Angeles Gay and Lesbian Center DBA 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: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD Inc
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Group
state: California
city: Oakland
country: United States
facility: Alameda County Medical Center
state: California
city: Oakland
country: United States
facility: East Bay AIDS Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California, Davis 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: Metropolitan Medical
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center, Clinical Trials Unit
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University HIV Clinical Trials Program
state: Connecticut
city: Stamford
country: United States
facility: The Stamford Hospital
state: Connecticut
city: Washington
country: United States
facility: Dupont Circle Physicians Group
state: District of Columbia
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates, PC
state: District of Columbia
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Health/Comprehensive Care Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond,M.D., P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami Beach
country: United States
facility: Wohlfeiler, Piperato and Associates, 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/ ValueHealthMD, LLC
state: Florida
city: Tampa
country: United States
facility: University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department
state: Florida
city: Tampa
country: United States
facility: Infectious Disease Research Institute Inc.
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Disease Consultants
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Infectious Disease Solutions, PC
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Honolulu
country: United States
facility: Leahi Hospital
state: Hawaii
city: Chicago
country: United States
facility: Ruth M. Rothstein CORE Center
state: Illinois
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Infectious Diseases Clinical Research
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
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: St. Louis
country: United States
facility: CentralWest Clinical Research
state: Missouri
city: St. Louis
country: United States
facility: Division of Infectious Diseases, St. Louis University Medical Center
state: Missouri
city: St. Louis
country: United States
facility: Southampton Healthcare
state: Missouri
city: Hillsborough
country: United States
facility: ID Care
state: New Jersey
city: Newark
country: United States
facility: Saint Michaels Medical Center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Voorhees
country: United States
facility: Garden State Infectious Diseases Associates, PA
state: New Jersey
city: Albany
country: United States
facility: Upstate ID Association
state: New York
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Bronx
country: United States
facility: Montiefiore Medical Center- AIDS Center
state: New York
city: Brooklyn
country: United States
facility: STAR Health Care Center (SUNY Downstate)
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Mount Vernon
country: United States
facility: Greiger Clinic
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Chelsea Village Medical, PC
state: New York
city: Rochester
country: United States
facility: AIDS Care
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center-Myers Park
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Philadelphia
country: United States
facility: Division of Infectious Diseases, Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Columbia
country: United States
facility: University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Nicholaos C. Bellos, MD, PA (Southwest Infectious Disease Clinical Research, Inc.)
state: Texas
city: Dallas
country: United States
facility: Trinity Health and Wellness Center/AIDS Arms, Inc.
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Harlingen
country: United States
facility: Garcia's Family Health Group
state: Texas
city: Houston
country: United States
facility: Dr. Joseph C. Gathe MD (Therapeutic Concepts, PA)
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education, Infectious Diseases (CARE-ID)
state: Virginia
city: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical practice
state: New South Wales
city: Darlinghurst
country: Australia
facility: National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales
state: New South Wales
city: Sydney
country: Australia
facility: Albion Street Centre
state: New South Wales
city: Sydney
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Carlton
country: Australia
facility: Melbourne Health - Royal Melbourne Hospital Campus (Sexual Health Clinic)
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Northside Clinic
state: Victoria
city: Darlinghurst
country: Australia
facility: Taylor Square Private Clinica
city: Graz
country: Austria
facility: LKH Graz West
city: Vienna
country: Austria
facility: Department of Dermatology, Division of Immunology, Allergy & Inf. Diseases; Medical University Vienna
city: Vienna
country: Austria
facility: Interne Lungenabteilung, SMZ Baumgartner Hoehe - Otto-Wagner-Spital
city: Brussels
country: Belgium
facility: CHU Saint-Pierre University Hospital
city: Brussels
country: Belgium
facility: Hôpital Universitaire Erasme - ULB
city: Ghent
country: Belgium
facility: University of Ghent
city: Calgary
country: Canada
facility: Southern Alberta Clinic
state: Alberta
city: Winnipeg
country: Canada
facility: Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg
state: Manitoba
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Canadian Immunodeficiency Research Collaborative (CIRC) Inc.
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Clinique medicale l'Actuel
state: Quebec
city: Montreal
country: Canada
facility: Clinique Medicale du Quartier Latin
state: Quebec
city: Copenhagen
country: Denmark
facility: Epidemiklinikken 5112, Rigshospitalet
city: Caen
country: France
facility: Service des Maladies Infectieuses, CHU de Caen
city: Lyon
country: France
facility: Hôpital de la Croix Rousse - Maladies Infectieuses et Tropicales
city: Montpellier
country: France
facility: CHU Gui de Chauliac, Maladies Infectieuses Dpt
city: Nantes
country: France
facility: CHU de Nantes Hopital de l'Hotel Dieu
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice
city: Paris
country: France
facility: Department of Infectious Diseases, Saint-Louis hospital
city: Paris
country: France
facility: Hopital Saint Antoine, Service De Maladies Infectieuses
city: Paris
country: France
facility: Bichat Hospital
city: Paris
country: France
facility: Tenon Hospital, UPMC
city: Paris
country: France
facility: Hopital Pitie-Salpetriere
city: Tourcoing
country: France
facility: Centre Hospitalier de Tourcoing
city: Bonn
country: Germany
facility: University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic
city: Duesseldorf
country: Germany
facility: Center for HIV and Hepatogastroenterology
city: Frankfurt am Main
country: Germany
facility: Infektio Research GmbH / Infektiologikum Frankfurt
city: Frankfurt am Main
country: Germany
facility: Klinikum der Goethe-Universitaet, Medizinische Klinik II, Schwerpunkt HIV, Haus 68
city: Hamburg
country: Germany
facility: ICH Study Center Hamburg
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit
city: Köln
country: Germany
facility: University of Cologne, Department of Internal Medicine
city: München
country: Germany
facility: MUC Research GmbH
city: Milan
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Rome
country: Italy
facility: National Institute for Infectious Diseases "L. Spallanzani" IRCCS
city: Torino
country: Italy
facility: Dipartimento di Malattie Infettive
city: Guadalajara
country: Mexico
facility: Unidad de VIH, Hospital Civil de Guadalajara, Fray Antonio Alcalde
state: Jalisco
city: Amsterdam
country: Netherlands
facility: Onze lieve vrouw gasthuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC, Internal Medicine, Section of Infectious Diseases
city: Porto
country: Portugal
facility: Serviço de Doenças Infecciosas, Hospital de São João
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: VA Caribbean Healthcare System
city: Stockholm
country: Sweden
facility: Venhälsan, Södersjukhuset
city: Lausanne
country: Switzerland
facility: CHUV
state: VD
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
state: East Sussex
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
state: Lancashire
city: London
country: United Kingdom
facility: Barts and the London NHS Trust
city: London
country: United Kingdom
facility: Homerton University Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital Foundation Trust
city: London
country: United Kingdom
facility: St. Mary's Hospital, London (Imperial College, London)
Study officials:
affiliation: Gilead Sciences
name: Marshall Fordyce, MD
role: STUDY_DIRECTOR
References:
citation: DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Yale K, Szwarcberg J, White K, Cheng AK, Kearney BP; GS-236-0103 Study Team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012 Jun 30;379(9835):2429-2438. doi: 10.1016/S0140-6736(12)60918-0.
citation: Rockstroh JK, DeJesus E, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Plummer A, Abram M, Cheng AK, Fordyce MW, Szwarcberg J; GS-236-0103 Study Team. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):483-6. doi: 10.1097/QAI.0b013e318286415c.
citation: Clumeck N, Molina JM, Henry K, Gathe J, Rockstroh JK, DeJesus E, Wei X, White K, Fordyce MW, Rhee MS, Szwarcberg J; GS-236-0103 Study Team. A randomized, double-blind comparison of single-tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF for initial treatment of HIV-1 infection: analysis of week 144 results. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e121-4. doi: 10.1097/QAI.0000000000000089. No abstract available.