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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01106586
• Other study ID #: GS-US-236-0103
• Status: Completed
• Phase: Phase 3
• First received: April 14, 2010
• Last updated: October 9, 2015
• Start date: April 2010
• Est. completion date: September 2014

Study information

• Verified date: October 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 708
• Est. completion date: September 2014
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV
• HIV Infections

Intervention

Drug:
• Stribild
Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR administered orally once daily
• ATV
Atazanavir 300 mg capsule administered orally once daily
• Ritonavir
Ritonavir (RTV; /r) 100 mg tablet administered orally once daily
• FTC/TDF
FTC/TDF 200/300 mg tablet administered orally once daily
• Stribild Placebo
Placebo to match Stribild administered orally once daily
• ATV Placebo
Placebo to match ATV administered orally once daily
• RTV Placebo
Placebo to match RTV administered orally once daily
• FTC/TDF Placebo
Placebo to match FTC/TDF administered orally once daily

Locations

Country	Name	City	State
Australia	Melbourne Health - Royal Melbourne Hospital Campus (Sexual Health Clinic)	Carlton	Victoria
Australia	Holdsworth House Medical practice	Darlinghurst	New South Wales
Australia	National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales	Darlinghurst	New South Wales
Australia	Taylor Square Private Clinica	Darlinghurst
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Northside Clinic	Melbourne	Victoria
Australia	Albion Street Centre	Sydney	New South Wales
Australia	East Sydney Doctors	Sydney	New South Wales
Austria	LKH Graz West	Graz
Austria	Department of Dermatology, Division of Immunology, Allergy & Inf. Diseases; Medical University Vienna	Vienna
Austria	Interne Lungenabteilung, SMZ Baumgartner Hoehe - Otto-Wagner-Spital	Vienna
Belgium	CHU Saint-Pierre University Hospital	Brussels
Belgium	Hôpital Universitaire Erasme - ULB	Brussels
Belgium	University of Ghent	Ghent
Canada	Southern Alberta Clinic	Calgary	Alberta
Canada	Clinique Medicale du Quartier Latin	Montreal	Quebec
Canada	Clinique medicale l'Actuel	Montreal	Quebec
Canada	Canadian Immunodeficiency Research Collaborative (CIRC) Inc.	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network, Toronto General Hospital	Toronto	Ontario
Canada	Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg	Winnipeg	Manitoba
Denmark	Epidemiklinikken 5112, Rigshospitalet	Copenhagen
France	Service des Maladies Infectieuses, CHU de Caen	Caen
France	Hôpital de la Croix Rousse - Maladies Infectieuses et Tropicales	Lyon
France	CHU Gui de Chauliac, Maladies Infectieuses Dpt	Montpellier
France	CHU de Nantes Hopital de l'Hotel Dieu	Nantes
France	Centre Hospitalier Universitaire de Nice	Nice
France	Bichat Hospital	Paris
France	Department of Infectious Diseases, Saint-Louis hospital	Paris
France	Hopital Pitie-Salpetriere	Paris
France	Hopital Saint Antoine, Service De Maladies Infectieuses	Paris
France	Tenon Hospital, UPMC	Paris
France	Centre Hospitalier de Tourcoing	Tourcoing
Germany	University of Bonn, Dep. of Internal Medicine I, HIV-Outpatient Clinic	Bonn
Germany	Center for HIV and Hepatogastroenterology	Duesseldorf
Germany	Infektio Research GmbH / Infektiologikum Frankfurt	Frankfurt am Main
Germany	Klinikum der Goethe-Universitaet, Medizinische Klinik II, Schwerpunkt HIV, Haus 68	Frankfurt am Main
Germany	ICH Study Center Hamburg	Hamburg
Germany	University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit	Hamburg
Germany	University of Cologne, Department of Internal Medicine	Köln
Germany	MUC Research GmbH	München
Italy	Fondazione Centro San Raffaele del Monte Tabor	Milan
Italy	National Institute for Infectious Diseases "L. Spallanzani" IRCCS	Rome
Italy	Dipartimento di Malattie Infettive	Torino
Mexico	Unidad de VIH, Hospital Civil de Guadalajara, Fray Antonio Alcalde	Guadalajara	Jalisco
Netherlands	Onze lieve vrouw gasthuis	Amsterdam
Netherlands	Erasmus MC, Internal Medicine, Section of Infectious Diseases	Rotterdam
Portugal	Serviço de Doenças Infecciosas, Hospital de São João	Porto
Puerto Rico	Clinical Research Puerto Rico	San Juan
Puerto Rico	VA Caribbean Healthcare System	San Juan
Sweden	Venhälsan, Södersjukhuset	Stockholm
Switzerland	CHUV	Lausanne	VD
Thailand	Ramathibodi Hospital, Mahidol University	Bangkok
Thailand	Siriraj Hospital	Bangkok
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton	East Sussex
United Kingdom	Barts and the London NHS Trust	London
United Kingdom	Chelsea and Westminster Hospital Foundation Trust	London
United Kingdom	Homerton University Hospital	London
United Kingdom	St. Mary's Hospital, London (Imperial College, London)	London
United Kingdom	North Manchester General Hospital	Manchester	Lancashire
United States	Summa Health System	Akron	Ohio
United States	Albany Medical College	Albany	New York
United States	Upstate ID Association	Albany	New York
United States	Clinical Alliance for Research & Education, Infectious Diseases (CARE-ID)	Annandale	Virginia
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Infectious Disease Solutions, PC	Atlanta	Georgia
United States	Be Well Medical Center	Berkley	Michigan
United States	AHF Research Center	Beverly Hills	California
United States	Montiefiore Medical Center- AIDS Center	Bronx	New York
United States	STAR Health Care Center (SUNY Downstate)	Brooklyn	New York
United States	Carolinas Medical Center-Myers Park	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	University of South Carolina	Columbia	South Carolina
United States	CSI Clinical Trials, Inc.	Costa Mesa	California
United States	Nicholaos C. Bellos, MD, PA (Southwest Infectious Disease Clinical Research, Inc.)	Dallas	Texas
United States	Trinity Health and Wellness Center/AIDS Arms, Inc.	Dallas	Texas
United States	Apex Research, LLC	Denver	California
United States	National Jewish Health	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Broward Health/Comprehensive Care Center	Fort Lauderdale	Florida
United States	Gary J. Richmond,M.D., P.A.	Fort Lauderdale	Florida
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	East Carolina University	Greenville	North Carolina
United States	Garcia's Family Health Group	Harlingen	Texas
United States	Kaiser Permanente Hospital	Hayward	California
United States	ID Care	Hillsborough	New Jersey
United States	Leahi Hospital	Honolulu	Hawaii
United States	Dr. Joseph C. Gathe MD (Therapeutic Concepts, PA)	Houston	Texas
United States	Gordon E. Crofoot MD PA	Houston	Texas
United States	Research Access Network	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Health for Life Clinic PLLC	Little Rock	Arkansas
United States	Living Hope Clinical Foundation	Long Beach	California
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Anthony Mills MD Inc	Los Angeles	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente	Los Angeles	California
United States	Los Angeles Gay and Lesbian Center DBA Jeffrey Goodman Special Care Clinic	Los Angeles	California
United States	Peter J Ruane, MD, Inc	Los Angeles	California
United States	Mercer University School of Medicine	Macon	Georgia
United States	North Shore University Hospital	Manhasset	New York
United States	The Kinder Medical Group	Miami	Florida
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Greiger Clinic	Mount Vernon	New York
United States	Yale University HIV Clinical Trials Program	New Haven	Connecticut
United States	Beth Israel Medical Center	New York	New York
United States	Chelsea Village Medical, PC	New York	New York
United States	Saint Michaels Medical Center	Newark	New Jersey
United States	Orange Coast Medical Group	Newport Beach	California
United States	Alameda County Medical Center	Oakland	California
United States	East Bay AIDS Center	Oakland	California
United States	IDOCF/ ValueHealthMD, LLC	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Division of Infectious Diseases, Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Spectrum Medical Group	Phoenix	Arizona
United States	AIDS Care	Rochester	New York
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	University of California, Davis Medical Center	Sacramento	California
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Kaiser Permanente Medical Center, Clinical Trials Unit	San Francisco	California
United States	Metropolitan Medical	San Francisco	California
United States	Peter Shalit, M.D.	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Baystate Infectious Diseases Clinical Research	Springfield	Massachusetts
United States	The Research Institute	Springfield	Massachusetts
United States	CentralWest Clinical Research	St. Louis	Missouri
United States	Division of Infectious Diseases, St. Louis University Medical Center	St. Louis	Missouri
United States	Southampton Healthcare	St. Louis	Missouri
United States	The Stamford Hospital	Stamford	Connecticut
United States	Infectious Disease Research Institute Inc.	Tampa	Florida
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department	Tampa	Florida
United States	Treasure Coast Infectious Disease Consultants	Vero Beach	Florida
United States	Garden State Infectious Diseases Associates, PA	Voorhees	New Jersey
United States	Capital Medical Associates, PC	Washington	District of Columbia
United States	Dupont Circle Physicians Group	Washington	District of Columbia
United States	George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Whitman Walker Clinic	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Italy,  Mexico,  Netherlands,  Portugal,  Puerto Rico,  Sweden,  Switzerland,  Thailand,  United Kingdom, 

References & Publications (3)

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 v — View 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 ritonav — View 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/tenofovi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Week 48	No
Secondary	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		Week 96	No
Secondary	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		Week 144	No
Secondary	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		Week 192	No
Secondary	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		Week 48	No
Secondary	The Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Weeks 48, 96, 144, and 192	Change = value of the relevant time point minus the baseline value	Baseline; Weeks 48, 96, 144, and 192	No
Secondary	The Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48		Week 48	No