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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome
• Intervention / Treatment: Drug: FTC/TDF; Drug: Stribild; Drug: NNRTI

• Study Type: Interventional
• Enrollment (Actual): 439
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst, Australia, NSW 2010
    • Holdsworth House Medical Practice
  • South Yarra, Australia, VIC 3141
    • Prahran Market Clinic
  • Sydney, Australia, NSW 2010
    • East Sydney Doctors
• Austria
  • Wien, Austria, 1090
    • Medical University of Vienna
  • Wien, Austria, 1140
    • Otto Wagner Spital
• Belgium
  • Antwerpen, Belgium, 2000
    • SEAMEO Regional Centre for Tropical Medicine
  • Bruxelles, Belgium, 1050
    • Hôpitaux IRIS Sud
  • Leuven, Belgium, 3000
    • University Hospital of Leuven
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Center
    • Toronto, Ontario, Canada, M5B1L6
      • Maple Leaf Medical Clinic
  • Quebec
    • Montreal, Quebec, Canada, H2L 5B1
      • Clinique Medicale du Quartier Latin
• France
  • Besancon, France, 25030
    • CHU de Besancon - Hopital Saint-Jacques
  • Bordeaux, France, 33079
    • Groupe Hospitalier Pellegrin
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Paris, France, 75018
    • Hopital Bichat Claude Bernard
• Germany
  • Berlin, Germany, 12157
    • EPIMED GmbH
  • Berlin, Germany, 13353
    • MIB Dienstleistung GmbH
  • Bonn, Germany, 53127
    • Medizinische Universitätsklinik
  • Frankfurt, Germany, 60596
    • Infektiologikum
  • Freiburg, Germany, 79106
    • Universitatsklinikum Freiburg
  • Hamburg, Germany, 20146
    • ICH Study Center
  • München, Germany, 80335
    • MUC Research GmbH
• Italy
  • Busto Arsizio/Varese, Italy, 21052
    • Azienda Ospedaliera Ospedale di Circolo Busto Arsizio
  • Milano, Italy, 20157
    • Ospedale Luigi Sacco
  • Milano, Italy, 20127
    • Fondazione Centro San Raffaele del Monte Tabor
  • Roma, Italy, 00149
    • Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS
  • Rome, Italy, 1214
    • Policlinico Universitario Agostino Gemelli
• Portugal
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria - CHLN EPE
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico Inc
• Spain
  • Barcelona, Spain, 8003
    • Hospital del Mar
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Valencia, Spain, 46009
    • Hospital La Fe de Valencia
  • Cataluña
    • Barcelona, Cataluña, Spain, 08025
      • Hospital De La Santa Creu I Sant Pau
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Hospital Clinico Universitario de Santiago
• United Kingdom
  • Brighton, United Kingdom, BN2 1ES
    • Brighton and Sussex University Hospitals NHS Trust
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • London, United Kingdom, SW10 9TH
    • Chelsea & Westminster Hospital
  • London, United Kingdom, E9 6SR
    • Homerton University Hospital
  • London, United Kingdom, SE1 1EE
    • South London Healthcare NHS Trust
  • London, United Kingdom, SE17EH
    • St. Thomas' Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Research Center
    • Beverly Hills, California, United States, 90211
      • Pacific Oak Medical Group
    • Hayward, California, United States, 94545
      • Kaiser Permanente
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane, MD, Inc.
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD Inc
    • Los Angeles, California, United States, 90059
      • OASIS Clinic
    • Oakland, California, United States, 94602
      • Alameda County 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, 94118
      • Kaiser Permanente
    • San Francisco, California, United States, 94109
      • Metropolis Medical
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physicians Group, P.C.
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, P.C.
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary Richmond MD, PA, Inc
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research
    • Miami, Florida, United States, 33133
      • The Kinder Medical Group
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • ValuHealth MD, LLC
    • Pensacola, Florida, United States, 32504
      • Infectious Diseases Associates of Northwest Florida
    • Safety Harbor, Florida, United States, 34684
      • Health Positive
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group, PC
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • HIV Program Hennepin County Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • The Kansas City Free Health Clinic
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • ID Care
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New York
    • Mt. Vernon, New York, United States, 10550
      • Greiger Clinic
    • New York, New York, United States, 10016
      • Aaron Diamond AIDS Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • ID Consultants, P.A.
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • Texas
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Clinical Researach Inc
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD, PA
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Clinical Alliance for Research & Education - Infectious Disease

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Stribild; Participants will switch from their baseline treatment regimen to Stribild for up to 96 weeks, and may continue to receive Stribild in the extension phase.	Drug: Stribild; Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with food
ACTIVE_COMPARATOR: NNRTI+FTC/TDF; Participants will stay on their baseline treatment regimen antiretroviral regimen consisting of an NNRTI plus FTC/TDF for up to 96 weeks, and may switch to Stribild in the extension phase.	Drug: FTC/TDF; FTC/TDF (200/300 mg) administered according to prescribing information; Other Names: Truvada; Drug: Stribild; Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with food; Drug: NNRTI; NNRTI agents administered according to prescribing information; allowed NNRTIs include efavirenz (EFV), nevirapine, or rilpivirine.

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 FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Change From Baseline in CD4+ Cell Count at Week 96		Baseline; Week 96
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96	The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.	Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Damian McColl, Gilead Sciences

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: December 14, 2011
• First Submitted That Met QC Criteria: December 16, 2011
• First Posted (ESTIMATE): December 20, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 7, 2016
• Last Update Submitted That Met QC Criteria: December 1, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment Experienced
• 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; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: GS-US-236-0121; 2011-004963-56 (EUDRACT_NUMBER)