Safety and Efficacy of COBI-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9350-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

The objective of this study is to evaluate the safety and efficacy of a regimen containing cobicistat-boosted atazanavir (ATV+COBI) plus emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) fixed-dose combination (FDC) versus ritonavir-boosted atazanavir (ATV+RTV) plus FTC/TDF FDC in HIV-1 infected, antiretroviral treatment-naive adults.

Participants will be randomized in a 1:1 ratio. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening.

Study Overview

• Status: Completed
• Conditions: HIV Infections; HIV
• Intervention / Treatment: Drug: COBI; Drug: ATV; Drug: FTC/TDF; Drug: RTV placebo; Drug: RTV; Drug: COBI placebo

• Study Type: Interventional
• Enrollment (Actual): 698
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Taylor Square Private Clinic
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital, Sydney
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
    • Sydney, New South Wales, Australia, 2010
      • Albion Street Centre
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Melbourne Sexual Health Centre
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3068
      • Northside Clinic
• Austria
  • Graz, Austria, A-8010
    • LKH Graz West
  • Vienna, Austria, 1090
    • Allgemeines Krankenhaus
  • Vienna, Austria, 1140
    • Interne Lungenabteilung, SMZ Baumgartner Hoehe - Otto-Wagner-Spital
• Belgium
  • Brussels, Belgium, 1000
    • CHU Saint-Pierre University Hospital
  • Brussels, Belgium, 1070
    • Hôpital Universitaire Erasme - ULB
  • Ghent, Belgium, 9000
    • University of Ghent
• Brazil
  • Campinas, Brazil, 13083-970
    • Universidade Estadual De Campinas
  • São Paulo, Brazil, 01246-900
    • Instituto De Infectologia Emilo Ribas
  • São Paulo, Brazil, 01416-000
    • Brasilmed Assistencia Medica E Pesquisas
  • São Paulo, Brazil, 04121-000
    • Crt-Dst/Aids
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21040-900
      • Instituto de Pesquisa Clínica Evandro Chagas
  • Sao Paulo
    • Santo Andre, Sao Paulo, Brazil, 09060-650
      • URDIP Faculdade de Medicina do ABC
• Canada
  • Montreal, Canada, H3H 1V1
    • Project LORI
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network, Toronto General Hospital
    • Toronto, Ontario, Canada, M5B1L6
      • Canadian Immunodeficiency Research Collaborative (CIRC) Inc.
  • Quebec
    • Montreal, Quebec, Canada, H2L 5B1
      • Clinique Medicale du Quartier Latin
    • Montreal, Quebec, Canada, H2L 4P9
      • Clinique Médicale L'Actuel
    • Montréal, Quebec, Canada, H2X 2P4
      • Immunodeficiency Service, McGill University Health Centre (MUHC) - Montreal Chest Institute
• Denmark
  • Copenhagen, Denmark, 2000
    • Rigshospitalet, Infektionsklinik 5112
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Instituto Dominicano de Estudios Virologicos - IDEV
• France
  • Caen, France, 14033
    • Service des Maladies Infectieuses, CHU de Caen
  • Lyon, France, 69288
    • Hôpital de la Croix Rousse - Maladies Infectieuses et Tropicales
  • Marseille, France, 13009
    • Hopital Sainte Marguerite Service d'Immuno-Hématologie Clinique -CISIH
  • Nantes, France, 44093
    • CHU de Nantes Hopital de l'Hotel Dieu
  • Paris, France, 75018
    • Bichat Hospital
  • Paris, France, 75010
    • Department of Infectious Diseases, Saint-Louis hospital
  • Paris, France, 75012
    • Hopital Saint Antoine, Service De Maladies Infectieuses
  • Paris, France, 75020
    • Tenon Hospital, UPMC
  • Paris, France, 75651
    • Maladies Infectieuses Dpt
  • Pessac, France, 33604
    • Centre François Magendie, Hôpital du Haut Lévêque
  • Tourcoing, France, 59208
    • Centre Hospitalier de Tourcoing
• Germany
  • Berlin, Germany, 12157
    • Epimed GmbH
  • Bonn, Germany, 53127
    • Medizinische Universitätsklinik
  • Frankfurt am Main, Germany, 60311
    • Infektio Research GmbH / Infektiologikum Frankfurt
  • Hamburg, Germany, 20146
    • ICH Study Center Hamburg
  • Hamburg, Germany, 20246
    • University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit
  • Koln, Germany, 50937
    • University of Cologne, Department of Internal Medicine
• Italy
  • Milan, Italy, 20127
    • Fondazione Centro San Raffaele del Monte Tabor
  • Milano, Italy, 20157
    • Azienda Ospedaliera Luigi Sacco 1° Divisione Malattie Infettive
  • Roma, Italy, 00149
    • Istituto Nazionale Malattie Infettive Lazzaro Spallanzani
  • Torino, Italy, 10149
    • Dipartimento di Malattie Infettive
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Unidad de VIH, Hospital Civil de Guadalajara, Fray Antonio Alcalde
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Onze Lieve Vrouw Gasthuis
• Portugal
  • Lisbon, Portugal, 1649-035
    • Hospital de Santa Maria - CHLN
  • Porto, Portugal, 4202-451
    • Serviço de Doenças Infecciosas, Hospital de São João
• Puerto Rico
  • Ponce, Puerto Rico, 00731
    • Instituto de Investigacion Clentifica del Sur
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
• Switzerland
  • Bern, Switzerland, 3010
    • Universitätsklinik für Infektiologie, Universitätsspital Bern
  • Zürich, Switzerland, 8091
    • Division of Infectious Diseases and Hospital Hygiene; University Hospital of Zurich
  • VD
    • Lausanne, VD, Switzerland, 1011
      • CHUV
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital, Mahidol University
  • Bangkok, Thailand, 10330
    • HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine Chulalongkorn University
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai University, Faculty of Medicine, Department of Medicine
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University
• United Kingdom
  • London, United Kingdom, E1 1BB
    • Barts and The London NHS Trust
  • London, United Kingdom, E9 6SR
    • Homerton University Hospital
  • London, United Kingdom, SE1 7EH
    • Guys and St. Thomas' NHS Trust
  • London, United Kingdom, SW17 0QT
    • Courtyard Clinic, St. Georges Hospital
  • East Sussex
    • Brighton, East Sussex, United Kingdom, BN2 1ES
      • Brighton and Sussex University Hospitals NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
      • Health For Life Clinic Pllc
  • California
    • Long Beach, California, United States, 90813
      • Living Hope Clinical Foundation
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD Inc
    • Los Angeles, California, United States, 90059
      • OASIS Clinic
    • Los Angeles, California, United States, 90028
      • Los Angeles Gay and Lesbian Center DBA Jeffrey Goodman Special Care Clinic
    • Los Angeles, California, United States, 90036
      • Peter J Ruane, MD, Inc
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Group
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
    • San Francisco, California, United States, 94115
      • Metropolis Medical
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Center, Clinical Trials Unit
  • Colorado
    • Denver, Colorado, United States, 80220
      • Apex Research, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
    • Washington, District of Columbia, United States, 20009
      • Whitman-Walker Clinic
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physicians Group
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center
    • Fort Lauderdale, Florida, United States, 33311
      • Broward Health/Comprehensive Care Center
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • Idocf/ Valuhealthmd, Llc
    • Tampa, Florida, United States, 33614
      • Infectious Disease Research Institute Inc.
    • Tampa, Florida, United States, 33602
      • University of South Florida HIV Clinical Research Unit / Hillsborough County Health Department
    • Tampa, Florida, United States, 33615
      • St. Joseph's Comprehensive Research Institute
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31210
      • Mercer University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative of New England
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63108
      • CentralWest Clinical Research
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michaels Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - AIDS Center
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10011
      • Ricky K. Hsu, MD, PC
    • New York, New York, United States, 10011
      • Chelsea Village Medical, PC
    • New York, New York, United States, 10011
      • Mt Sinai School of Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center-Myers Park
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University, The Brody School of Medicine
    • Huntersville, North Carolina, United States, 28078
      • Rosedale Infectious Diseases
    • Winston Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
    • Philadelphia, Pennsylvania, United States, 19107
      • Division of Infectious Diseases, Thomas Jefferson University
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75204
      • Southwest Infectious Disease Clinical Research, Inc.
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Harlingen, Texas, United States, 78550
      • Garcia's Family Health Group
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
    • Houston, Texas, United States, 77098
      • Research Access Network
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, M.D.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 ECG
• Adequate renal function (eGFR calculated using the Cockcroft-Gault equation ≥ 70 mL/min)
• 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
• 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 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)
• Have an implanted defibrillator or pacemaker
• Have an ECG PR interval ≥ 220 msec
• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study 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, 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.
• Medications contraindicated for use with COBI, emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), atazanavir (ATV), ritonavir (RTV) or subjects with any known allergies to the excipients of COBI tablets, Truvada tablets, atazanavir capsules or ritonavir tablets.
• Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial.
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ATV+COBI+FTC/TDF; COBI + RTV placebo + ATV + FTC/TDF once daily	Drug: COBI; Cobicistat (COBI) 150 mg tablet administered orally once daily; Other Names: Tybost®; GS-9350; Drug: ATV; Atazanavir (ATV) 300 mg capsule administered orally once daily; Other Names: Reyataz®; Drug: FTC/TDF; Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily; Other Names: Truvada®; Drug: RTV placebo; Placebo to match RTV administered orally once daily
ACTIVE_COMPARATOR: ATV+RTV+FTC/TDF; RTV + COBI placebo + ATV + FTC/TDF once daily	Drug: ATV; Atazanavir (ATV) 300 mg capsule administered orally once daily; Other Names: Reyataz®; Drug: FTC/TDF; Emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg fixed-dose combination tablet administered orally once daily; Other Names: Truvada®; Drug: RTV; Ritonavir (RTV) 100 mg tablet administered orally once daily; Other Names: Norvir®; Drug: COBI placebo; Placebo to match COBI administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the prespecified time point within an allowed window of time, along with study drug discontinuation status.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CD4 Cell Count at Week 48		Baseline to Week 48
Change From Baseline in CD4 Cell Count at Week 96		Baseline to Week 96
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm.	Week 96
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 144 was analyzed using the snapshot algorithm.	Week 144
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 192 was analyzed using the snapshot algorithm.	Week 192
Change From Baseline in CD4 Cell Count at Week 144		Baseline to Week 144
Change From Baseline in CD4 Cell Count at Week 192		Baseline to Week 192

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Gallant JE, Koenig E, Andrade-Villanueva J, Chetchotisakd P, DeJesus E, Antunes F, Arasteh K, Moyle G, Rizzardini G, Fehr J, Liu Y, Zhong L, Callebaut C, Szwarcberg J, Rhee MS, Cheng AK. Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1-infected patients: week 48 results. J Infect Dis. 2013 Jul;208(1):32-9. doi: 10.1093/infdis/jit122. Epub 2013 Mar 26.
• Gallant JE, Koenig E, Andrade-Villanueva JF, Chetchotisakd P, DeJesus E, Antunes F, Arasteh K, Rizzardini G, Fehr J, Liu HC, Abram ME, Cao H, Szwarcberg J. Brief Report: Cobicistat Compared With Ritonavir as a Pharmacoenhancer for Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate: Week 144 Results. J Acquir Immune Defic Syndr. 2015 Jul 1;69(3):338-40. doi: 10.1097/QAI.0000000000000598.
• Gallant J, Moyle G, Berenguer J, Shalit P, Cao H, Liu YP, Myers J, Rosenblatt L, Yang L, Szwarcberg J. Atazanavir Plus Cobicistat: Week 48 and Week 144 Subgroup Analyses of a Phase 3, Randomized, Double-Blind, Active-Controlled Trial. Curr HIV Res. 2017;15(3):216-224. doi: 10.2174/1570162X14666161021102728.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): November 1, 2011
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: April 20, 2010
• First Submitted That Met QC Criteria: April 20, 2010
• First Posted (ESTIMATE): April 22, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 23, 2016
• Last Update Submitted That Met QC Criteria: April 15, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Treatment Naive; HIV 1 Infected
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Cobicistat; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Atazanavir Sulfate
• Other Study ID Numbers: GS-US-216-0114; 2009-016759-22 (EUDRACT_NUMBER)