Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients

HIV Infections Clinical Trial

Official title:

A Phase 3b Randomized, Open-Label Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor (PI + RTV) Plus Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (EVG/COBI/FTC/TDF) in Virologically-Suppressed, HIV-1 Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01475838
• Other study ID #: GS-US-236-0115
• Secondary ID: 2011-004483-30
• Status: Completed
• Phase: Phase 3
• First received: November 17, 2011
• Last updated: December 1, 2015
• Start date: November 2011
• Est. completion date: December 2014

Study information

• Verified date: December 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

This study will evaluate the non-inferiority of Stribild® (elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) single-tablet regimen (STR) relative to regimens consisting of a protease inhibitor (PI) boosted with ritonavir (RTV) plus Truvada® (FTC/TDF) fixed-dose combination 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 438
• Est. completion date: December 2014
• Est. primary completion date: November 2013
• 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

• Be on a stable antiretroviral regimen consisting of a ritonavir boosted PI plus FTC/TDF continuously for = 6 consecutive months preceding the screening visit

• Be on the first or second antiretroviral drug regimen 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, or normal direct bilirubin

• Adequate hematologic function

• Serum amylase = 5 × ULN

• Estimated glomerular filtration rate = 70 mL/min

• Females of childbearing potential must agree to utilize highly effective contraception methods, or be nonheterosexually active, practice sexual abstinence from screening throughout the duration of the study period and for 30 days 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 a highly effective method of contraception during heterosexual intercourse from the screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product, or must be nonheterosexually active, or practice sexual abstinence

• Age = 18 years

Exclusion Criteria:

• A 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 participants 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, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma

• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline, except for intramuscular penicillin for the treatment of syphilis

• 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• PI
PI administered according to prescribing information; allowed PIs include atazanavir (ATV), darunavir (DRV), fosamprenavir (FPV), lopinavir (LPV), or saquinavir (SQV)
• RTV
RTV administered according to prescribing information FTC/TDF administered according to prescribing information
• FTC/TDF
FTC/TDF (200/300 mg) administered according to prescribing information
• Stribild
Stribild (E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with food

Locations

Country	Name	City	State
Austria	Innsbruck Medical University	Innsbruck
Austria	Univ.-Kklinik fuer Innere Medizin III	Salzburg
Austria	Medical University of Vienna	Vienna
Austria	Otto-Wagner-Spital	Wien
Belgium	UCL Saint Luc	Brussels
Belgium	University Hospital Ghent	Ghent
Belgium	CHU Sart Tilman	Liege
Canada	Clinique Medicale Du Quartier Latin	Montreal	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
France	CHU de Besancon, Hopital Saint-Jacques	Besançon
France	Hôpital de la Croix-Rousse	Lyon
France	CHU Hôpital Gui de Chauliac	Montpellier
France	Archet 1 Chu Nice Department of Infectology	Nice
France	Hôpital Bichat-Claude Bernard	Paris
France	Hopital Saint Antoine	Paris
France	hôpital Tenon	Paris
France	Saint-Louis Hospital	Paris
France	Maladies Infectieuses Dpt	Paris Cedex 13
France	Hôpital Haut Lévêque	Pessac
Germany	Epimed GmbH	Berlin
Germany	University of Bonn	Bonn
Germany	Universitätsklinikum Essen, Dermatologie, HIV Ambulanz	Essen
Germany	Johann Wolfgang Goethe-University Hospital / Infectious Diseases Hs 68	Frankfurt
Germany	ICH Study Center	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf, Ambulanzzentrum des UKE GmbH, Bereich Infektiologie	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Infektlonsambulanz Unlkllnik Koln	Koln
Germany	Infektionsambulanz, Med Poliklink, Klinikum der Universitat Munchnen	Munich
Italy	Ospedali Riuniti	Bergamo
Italy	Clinic of Infectious Diseases, University of Milan-San Paolo Hospital	Milano
Italy	Fondazione Centro San Raffaele	Milano
Italy	Ospedale Luigi Sacco	Milano
Italy	National Institute for Infectious Diseases "L. Spallanzani"	Rome
Italy	University of Torino, Dept of Infectious Disease	Torino
Portugal	HHP Hospital de Cascais	Alcabideche
Portugal	Hospital Santo Antonio Dos Capuchos, Centro Hospitalar de Lisboa	Lisboa
Portugal	Hospital de Santa Maria-CHLN, EPE	Lisbon
Puerto Rico	Clinical Research Puert Rico	San Juan
Puerto Rico	University of Puerto Rico School of Medicine	San Juan
Spain	Hospital General Universitario Alicante	Alicante
Spain	Hospital clinic	Barcelona
Spain	Hospital Germans Trias I Pujol	Barcelona
Spain	Hospital Universitari Bellvitge HIV Unit. Infectious Disease Service.	Barcelona
Spain	Hospital General Universitario de Elche	Elche, Alicante
Spain	Hospital La Paz	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Infectious Diseases Department, Hospital Carlos III	Madrid
Spain	Hospital Virgen del Rocio	Sevilla
Switzerland	Geneva University Hospital	Geneva
Switzerland	University Hospital of Zurich; Division of Infectious Diseases and Hospital Epidemiology	Zurich
Switzerland	Zentrum fur Infektionskrankheiten	Zurich
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton
United Kingdom	Chelsea and Westminster	London
United Kingdom	Royal Free Hampstead NHS Trust	London
United States	Atlanta ID Group	Atlanta	Georgia
United States	Be Well Medical Center	Berkley	Michigan
United States	AIDS Healthcare Foundation	Beverly Hills	California
United States	Pacific Oaks Medical Group	Beverly Hills	California
United States	ID Consultants, P.A.	Charlotte	North Carolina
United States	John H. Stroger, Jr. Hospital of Cook County/Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	Northwestern University Division of Infectious Diseases	Chicago	Illinois
United States	Southwest Infectious Disease Clinical Research, Inc	Dallas	Texas
United States	Uptown Physicians Group	Dallas	Texas
United States	Gary Richmond, MD	Fort Lauderdale	Florida
United States	Midway Immunology & Research Center, LLC	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	Kaiser Permanente	Hayward	California
United States	I.D. Care Associates PA	Hillsborough	New Jersey
United States	Gordon Crofoot Md, Pa	Houston	Texas
United States	St. Hope Foundation Inc	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	The Kansas City Free Health Clinic	Kansas City	Missouri
United States	Anthony Mills MD Inc	Los Angeles	California
United States	Kaiser Permanente	Los Angeles	California
United States	OASIS Clinic	Los Angeles	California
United States	Peter J. Ruane, M.D., Inc.	Los Angeles	California
United States	The Kinder Medical Group	Miami	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Greiger Clinic	Mt. Vernon	New York
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Idocf/Valuhealthmd, Llc	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Infectious Diseases Associates of NW FL, P.A.	Pensacola	Florida
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Pueblo Family Physicians	Phoenix	Arizona
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Kaiser Permanente	Sacramento	California
United States	University of California, Davis	Sacramento	California
United States	AHF Health Positive Tampa Bay	Safety Harbor	Florida
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Kaiser Permanente San Francisco	San Francisco	California
United States	Metropolis Medical	San Francisco	California
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	Capital Medical Associates, PC	Washington	District of Columbia
United States	Dupont Circle Physicians Group, P.C	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,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Portugal,  Puerto Rico,  Spain,  Switzerland,  United Kingdom, 

References & Publications (2)

Arribas JR, Pialoux G, Gathe J, Di Perri G, Reynes J, Tebas P, Nguyen T, Ebrahimi R, White K, Piontkowsky D. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor — View 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-nucle — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48	No
Secondary	Change From Baseline in CD4+ Cell Count at Week 96		Baseline; Week 96	No