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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01495702
• Other study ID #: GS-US-236-0121
• Secondary ID: 2011-004963-56
• Status: Completed
• Phase: Phase 3
• First received: December 14, 2011
• Last updated: December 1, 2015
• Start date: December 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 439
• 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 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 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:
• NNRTI
NNRTI agents administered according to prescribing information; allowed NNRTIs include efavirenz (EFV), nevirapine, or rilpivirine.
• FTC/TDF
FTC/TDF (200/300 mg) administered according to prescribing information
• Stribild
Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; E/C/F/TDF) (150/150/200/300 mg) STR administered orally once daily with food

Locations

Country	Name	City	State
Australia	Holdsworth House Medical Practice	Darlinghurst
Australia	Prahran Market Clinic	South Yarra
Australia	East Sydney Doctors	Sydney
Austria	Medical University of Vienna	Wien
Austria	Otto Wagner Spital	Wien
Belgium	SEAMEO Regional Centre for Tropical Medicine	Antwerpen
Belgium	Hôpitaux IRIS Sud	Bruxelles
Belgium	University Hospital of Leuven	Leuven
Canada	Clinique Medicale Du Quartier Latin	Montreal	Quebec
Canada	Maple Leaf Medical Clinic	Toronto	Ontario
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
France	CHU de Besancon - Hopital Saint-Jacques	Besancon
France	Groupe Hospitalier Pellegrin	Bordeaux
France	Hopital Bichat Claude Bernard	Paris
France	Hopital Saint Antoine	Paris
France	Hopital Saint Louis	Paris
Germany	EPIMED GmbH	Berlin
Germany	MIB Dienstleistung GmbH	Berlin
Germany	Medizinische Universitätsklinik	Bonn
Germany	Infektiologikum	Frankfurt
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	ICH Study Center	Hamburg
Germany	MUC Research GmbH	München
Italy	Azienda Ospedaliera Ospedale di Circolo Busto Arsizio	Busto Arsizio/Varese
Italy	Fondazione Centro San Raffaele del Monte Tabor	Milano
Italy	Ospedale Luigi Sacco	Milano
Italy	Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS	Roma
Italy	Policlinico Universitario Agostino Gemelli	Rome
Portugal	Hospital de Santa Maria - CHLN EPE	Lisboa
Puerto Rico	Clinical Research Puerto Rico Inc	San Juan
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña
Spain	Hospital del Mar	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela	Galicia
Spain	Hospital La Fe de Valencia	Valencia
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Chelsea & Westminster Hospital	London
United Kingdom	Homerton University Hospital	London
United Kingdom	South London Healthcare NHS Trust	London
United Kingdom	St. Thomas' Hospital	London
United States	Clinical Alliance for Research & Education - Infectious Disease	Annandale	Virginia
United States	Atlanta ID Group, PC	Atlanta	Georgia
United States	Be Well Medical Center	Berkley	Michigan
United States	AHF Research Center	Beverly Hills	California
United States	Pacific Oak Medical Group	Beverly Hills	California
United States	ID Consultants, P.A.	Charlotte	North Carolina
United States	Southwest Infectious Disease Clinical Researach Inc	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Gary Richmond MD, PA, Inc	Fort Lauderdale	Florida
United States	Midway Immunology and Research	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	Kaiser Permanente	Hayward	California
United States	ID Care	Hillsborough	New Jersey
United States	Gordon E. Crofoot MD, PA	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	OASIS Clinic	Los Angeles	California
United States	Peter J. Ruane, MD, Inc.	Los Angeles	California
United States	The Kinder Medical Group	Miami	Florida
United States	HIV Program Hennepin County Medical Center	Minneapolis	Minnesota
United States	Greiger Clinic	Mt. Vernon	New York
United States	Aaron Diamond AIDS Research Center	New York	New York
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Alameda County Medical Center	Oakland	California
United States	Orlando Immunology Center	Orlando	Florida
United States	ValuHealth MD, LLC	Orlando	Florida
United States	Infectious Diseases Associates of Northwest Florida	Pensacola	Florida
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	Health Positive	Safety Harbor	Florida
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Kaiser Permanente	San Francisco	California
United States	Metropolis Medical	San Francisco	California
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Capital Medical Associates, P.C.	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,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Italy,  Portugal,  Puerto Rico,  Spain,  United Kingdom, 

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