Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Adults

NCT ID: NCT02345226

Last Updated: 2020-01-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

881 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-26

Study Completion Date

2019-01-02

Brief Summary

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The primary objective of this study is to evaluate the non-inferiority of switching to emtricitabine/rilpivirine/tenofovir alafenamide (FTC/RPV/TAF) fixed dose combination (FDC) as compared to continuing the non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen of efavirenz /FTC/tenofovir disoproxil fumarate (EFV/FTC/TDF) FDC in virologically-suppressed HIV-1 infected participants.

Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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FTC/RPV/TAF

FTC/RPV/TAF plus EFV/FTC/TDF placebo for at least 96 weeks.

Group Type EXPERIMENTAL

FTC/RPV/TAF

Intervention Type DRUG

200/25/25 mg FDC tablets administered orally once daily

EFV/FTC/TDF Placebo

Intervention Type DRUG

Tablets administered orally once daily

EFV/FTC/TDF

EFV/FTC/TDF plus FTC/RPV/TAF placebo for at least 96 weeks.

Group Type ACTIVE_COMPARATOR

EFV/FTC/TDF

Intervention Type DRUG

600/200/300 mg FDC tablets administered orally once daily

FTC/RPV/TAF Placebo

Intervention Type DRUG

Tablets administered orally once daily

Open Label Extension Phase

After the Week 96 visit, participants will be given the option to receive open label FTC/RPV/TAF for up to an additional 48 weeks. In countries where FTC/RPV/TAF is not yet commercially available, participants will be given the option to receive open-label FTC/RPV/TAF and attend visits every 12 weeks until FTC/RPV/TAF becomes commercially available, or until Gilead elects to discontinue the study, whichever occurs first.

Group Type EXPERIMENTAL

FTC/RPV/TAF

Intervention Type DRUG

200/25/25 mg FDC tablets administered orally once daily

Interventions

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FTC/RPV/TAF

200/25/25 mg FDC tablets administered orally once daily

Intervention Type DRUG

EFV/FTC/TDF Placebo

Tablets administered orally once daily

Intervention Type DRUG

EFV/FTC/TDF

600/200/300 mg FDC tablets administered orally once daily

Intervention Type DRUG

FTC/RPV/TAF Placebo

Tablets administered orally once daily

Intervention Type DRUG

Other Intervention Names

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Odefsey® Atripla®

Eligibility Criteria

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Inclusion Criteria

* The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Currently receiving EFV/FTC/TDF FDC for ≥ 6 consecutive months preceding the screening visit
* Documented plasma HIV-1 RNA levels \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 6 months preceding the screening visit. Unconfirmed virologic elevation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable
* Have no documented resistance to any of the study agents at any time in the past
* HIV-1 RNA \< 50 copies/mL at the screening visit
* Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
* Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
* Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
* Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula

Exclusion Criteria

* Hepatitis B surface antigen (HBsAg) positive
* Hepatitis C antibody positive with detectable hepatitis C virus (HCV) RNA (individuals who have HCV antibody but no detectable HCV RNA are eligible to enroll)
* Individuals experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
* Females who are breastfeeding
* Positive serum pregnancy test
* Current alcohol or substance use judged by the Investigator to potentially interfere with the individual's study compliance
* A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/Day 1 and must not be anticipated to require systemic therapy during the study
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline/Day 1
* Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
* Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
* Individuals receiving ongoing therapy with any of the disallowed medications listed in the protocol, including drugs not to be used with FTC, RPV and/or TAF; or individuals with any known allergies to the excipients of FTC/RPV/TAF
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Maricopa Integrated Health System

Phoenix, Arizona, United States

Site Status

Spectrum Medical Group

Phoenix, Arizona, United States

Site Status

AHF Research Center

Beverly Hills, California, United States

Site Status

Pacific Oaks Medical Group

Beverly Hills, California, United States

Site Status

Long Beach Education and Research Consultants

Long Beach, California, United States

Site Status

Kaiser Permanente

Los Angeles, California, United States

Site Status

Southern California Men's Medical Group

Los Angeles, California, United States

Site Status

Tarrant County ID Associates

Los Angeles, California, United States

Site Status

Kaiser Permanente

Sacramento, California, United States

Site Status

University of California-UC Davis

Sacramento, California, United States

Site Status

La Playa Medical Group and Clinical Research

San Diego, California, United States

Site Status

Kaiser Permanente

San Francisco, California, United States

Site Status

Optimus Medical

San Francisco, California, United States

Site Status

Kaiser Permanente

San Leandro, California, United States

Site Status

Los Angeles BioMedical Institute at Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Apex Research Institute

Denver, Colorado, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

World Health Clinicians' CIRCLE CARE Center

Norwalk, Connecticut, United States

Site Status

Capital Medical Associates, P.C.

Washington D.C., District of Columbia, United States

Site Status

Medical Faculty Associates, Inc.

Washington D.C., District of Columbia, United States

Site Status

Whitman Walker Clinic

Washington D.C., District of Columbia, United States

Site Status

Gary Richmond, MD, PA, Inc.

Fort Lauderdale, Florida, United States

Site Status

Therafirst Medical Centers

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, United States

Site Status

AIDS Healthcare Foundation

Miami, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

AIDS Healthcare Foundation

Miami Beach, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

Infectious Diseases Associates of NW Florida, P.A.

Pensacola, Florida, United States

Site Status

Hillsborough County Health Dept.

Tampa, Florida, United States

Site Status

Infectious Disease Research Institute Inc.

Tampa, Florida, United States

Site Status

St. Joseph's Comprehensive Research Institute

Tampa, Florida, United States

Site Status

AIDS Research & Treatment Center of the Treasure Coast

Vero Beach, Florida, United States

Site Status

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Site Status

Rowan Tree Medical PA

Wilton Manors, Florida, United States

Site Status

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

Site Status

Atlanta ID Group

Atlanta, Georgia, United States

Site Status

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Site Status

Mercer University School of Medicine

Macon, Georgia, United States

Site Status

Chatham County Health Department

Savannah, Georgia, United States

Site Status

The CORE Foundation

Chicago, Illinois, United States

Site Status

Indiana University Medical Center

Indianapolis, Indiana, United States

Site Status

Boston University Medical Center

Boston, Massachusetts, United States

Site Status

Brigham and Women's

Boston, Massachusetts, United States

Site Status

MetroWest Medical Center

Framingham, Massachusetts, United States

Site Status

Baystate Infectious Diseases Clinical Research

Springfield, Massachusetts, United States

Site Status

The Research Institute

Springfield, Massachusetts, United States

Site Status

Be Well Medical Center

Berkley, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Southampton Healthcare, Inc.

St Louis, Missouri, United States

Site Status

Saint Michael's Medical Center

Newark, New Jersey, United States

Site Status

South Jersey Infectious Disease

Somers Point, New Jersey, United States

Site Status

Southwest CARE Center

Santa Fe, New Mexico, United States

Site Status

Upstate Infectious Diseases Associates

Albany, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Columbia University Medical Center/ New York Presbyterian

New York, New York, United States

Site Status

Jacobi Medical Center

The Bronx, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Infectious Disease Consultants, PA

Charlotte, North Carolina, United States

Site Status

The Brody School of Medicine

Greenville, North Carolina, United States

Site Status

Rosedale Infectious Diseases

Huntersville, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Central Texas Clinical Research

Austin, Texas, United States

Site Status

North Texas Infectious Diseases Consultants

Dallas, Texas, United States

Site Status

Southwest Infectious Disease Clinical Research, Inc.

Dallas, Texas, United States

Site Status

Trinity Health and Wellness Center/AIDS Arms, Inc.

Dallas, Texas, United States

Site Status

AIDS Arms, Inc./Trinity Health & Wellness Center

Fort Worth, Texas, United States

Site Status

Gordon E. Crofoot, MD, PA

Houston, Texas, United States

Site Status

Research Access Network

Houston, Texas, United States

Site Status

DCOL Center for Clinical Research

Longview, Texas, United States

Site Status

Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)

Annandale, Virginia, United States

Site Status

Peter Shalit, MD

Seattle, Washington, United States

Site Status

Premier Clinical Research

Spokane, Washington, United States

Site Status

CHU Saint-Pierre University Hospital

Brussels, , Belgium

Site Status

Cliniques Universitaires UCL Saint-Luc

Brussels, , Belgium

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Spectrum Health

Vancouver, British Columbia, Canada

Site Status

Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status

Maple Leaf Research

Toronto, Ontario, Canada

Site Status

University Health Network

Toronto, Ontario, Canada

Site Status

Clinique medicale l'Actuel

Montreal, Quebec, Canada

Site Status

Clinique OPUS

Montreal, Quebec, Canada

Site Status

McGill University Health Centre

Montreal, Quebec, Canada

Site Status

Hopital Bichat Claude Bernard

Paris, , France

Site Status

Hopital Saint Louis

Paris, , France

Site Status

Chu Tours

Tours, , France

Site Status

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH (zibp)

Berlin, , Germany

Site Status

University of Bonn

Bonn, , Germany

Site Status

Universitat zu Koln

Cologne, , Germany

Site Status

Center for HIV and Hepatogastroenterology

Düsseldorf, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Infektiologikum

Frankfurt, , Germany

Site Status

ICH Study Center Hamburg

Hamburg, , Germany

Site Status

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

MUC Research GmbH

München, , Germany

Site Status

Clinical Research Puerto Rico Inc

San Juan, , Puerto Rico

Site Status

Hope Clinical Research

San Juan, , Puerto Rico

Site Status

University of Puerto Rico School of Medicine

San Juan, , Puerto Rico

Site Status

Hospital General Universitario de Alicante

Alicante, , Spain

Site Status

Hospital Clinic i Provincial

Barcelona, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitary de Bellvitge

Barcelona, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

University Hospital Basel

Basel, , Switzerland

Site Status

Geneva University Hospital

Geneva, , Switzerland

Site Status

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Site Status

Barts & The London NHS Trust

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Mortimer Market Centre

London, , United Kingdom

Site Status

The Royal Free Hampstead NHS Trust

London, , United Kingdom

Site Status

Countries

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United States Belgium Canada France Germany Puerto Rico Spain Switzerland United Kingdom

References

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Hagins D, Orkin C, Daar ES, Mills A, Brinson C, DeJesus E, Post FA, Morales-Ramirez J, Thompson M, Osiyemi O, Rashbaum B, Stellbrink HJ, Martorell C, Liu H, Liu YP, Porter D, Collins SE, SenGupta D, Das M. Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials. HIV Med. 2018 Nov;19(10):724-733. doi: 10.1111/hiv.12664. Epub 2018 Aug 12.

Reference Type RESULT
PMID: 30101539 (View on PubMed)

Mills A, Brinson C, Martorell C, Crofoot G, Daar E, Osiyemi O, et al. Switching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF: Week 96 Results. Conference on Retroviruses and Opportunistic Infections, Boston. March 4-7, 2018, Abstract 504.

Reference Type RESULT

Arribas JR, Rockstroh J, Post, Yazdanpanah Y, Cavassini, DeJesus E, et al. Bone and renal safety of switching to rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF) from single-tablet regimens (STRs) containing efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) or rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF): Week 48 subgroup analysis in patients at risk of or with comorbidities. Abstract accepted for presentation at the 16th European AIDS Conference, 2017 25-27 October Milan, Italy.

Reference Type RESULT

Porter DP, KulkarniR, Cao H, SenGupta D, and White KL. No Emergent Resistance in HIV-1 Virologically-Suppressed Subjects Who Switched to RPV/FTC/TAF [Poster 1381]. ID Week 2017 4-8 October; San Diego, California.

Reference Type RESULT

E DeJesus, M Ramgopal, G Crofoot, P Ruane, A LaMarca. J-M Molina et al. Efficacy and Safety of Switching to RPV/FTC/TAF in Older Adults. 8th International Workshop on HIV and Aging 2017 2-3 October, New York, New York.

Reference Type RESULT

Molina JM, DeJesus E, Rijnders B, Post FAV, B., Stoeckle M, ThalmeA, et al. Efficacy and Safety of Switching From RPV/FTC/TDF or EFV/FTC/TDF to RPV/FTC/TAF in Black Adults [Presentation MOPEB0291]. 9th IAS Conference on HIV Science 2017 23-26 July Paris, France.

Reference Type RESULT

Rockstroh J, Orkin C, Yazdanpanah Y, Di Perri GDS, P. E., Arribas JR, Brinkman K, et al. Switching From TDF to TAF Improves Bone and Renal Safety Independent of Age, Sex, Race, or 3rd Agent: Results From Pooled Analysis (N=3816) of Virologically Suppressed HIV-1 Infected Adults [Presentation MOPEB0289]. 9th IAS Conference on HIV Science; 2017 23 26 July Paris, France.

Reference Type RESULT

DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Martorell CT, de Wet J, Stellbrink HJ, Molina JM, Post FA, Valero IP, Porter D, Liu Y, Cheng A, Quirk E, SenGupta D, Cao H. Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study. Lancet HIV. 2017 May;4(5):e205-e213. doi: 10.1016/S2352-3018(17)30032-2. Epub 2017 Mar 2.

Reference Type RESULT
PMID: 28259776 (View on PubMed)

Majeed SR, Shao Y, Garner W, Scott J, Pérez-Ruixo C, SenGupta D, et al. Evaluation of RPV/FTC/TAF Exposure-Efficacy and Exposure-Safety Relationships [Poster 427]. Conference on Retroviruses and Opportunistic Infections (CROI) 2017 13-16 February; Seattle, Washington.

Reference Type RESULT

Hagins D, Mills A, Martorell C, Walmsley S, Gallant J, Tebas P, et al. Efficacy and Safety of Switching to RPV/FTC/TAF in Women [Abstract 12]. 7th International Workshop on HIV & Women; 2017 11-12 February; Seattle, Washington.

Reference Type RESULT

Orkin C, DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, et al. 48 Week Results from two studies: Switching to RPV/FTC/TAF from EFV/FTC/TDF (Study 1160) or RPV/FTC/TDF (Study 1216) [Presentation]. HIV Glasgow; 2016 23-26 October; Glasgow, United Kingdom.

Reference Type RESULT

Other Identifiers

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2014-004779-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-366-1160

Identifier Type: -

Identifier Source: org_study_id

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