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Switch Study to Evaluate the Safety and Efficacy of Emtricitabine/Rilpivirine/Tenofovir Alafenamide (FTC/RPV/TAF) Fixed Dose Combination (FDC) in HIV-1 Positive Adults Who Are Virologically Suppressed on Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF)

Phase 3
Completed
Conditions
HIV-1 Infection
Interventions
Drug: FTC/RPV/TDF
Drug: FTC/RPV/TDF Placebo
Drug: FTC/RPV/TAF Placebo
Registration Number
NCT02345252
Lead Sponsor
Gilead Sciences
Brief Summary

The primary objective of this study is to evaluate the noninferiority of switching to emtricitabine/rilpivirine /tenofovir alafenamide (FTC/RPV/TAF) fixed-dose combination (FDC) as compared to continuing FTC/RPV/tenofovir disoproxil fumarate (TDF) FDC (FTC/RPV/TDF) in virologically suppressed HIV-1 infected participants.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
632
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 FTC/RPV/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. After reaching HIV-1 RNA < 50 copies/mL, single values of HIV-1 RNA ≥ 50 copies/mL followed by resuppression, are allowed
  • 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 (≤ 26 μmol/L), or normal direct bilirubin
  • Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3 (1.00 GI/L); platelets ≥ 50,000/mm^3 (50 GI/L); hemoglobin ≥ 8.5 g/dL (85 g/L))
  • 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 (1.17 mL/sec) according to the Cockcroft-Gault formula

Key

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 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

Note: Other Inclusion/Exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
FTC/RPV/TAFFTC/RPV/TDF PlaceboFTC/RPV/TAF plus FTC/RPV/TDF placebo for at least 96 weeks.
FTC/RPV/TDFFTC/RPV/TDFFTC/RPV/TDF plus FTC/RPV/TAF placebo for at least 96 weeks.
Open Label Extension PhaseFTC/RPV/TAFAfter the Week 96 visit is completed, 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 Sciences elects to discontinue the study, whichever occurs first.
FTC/RPV/TDFFTC/RPV/TAF PlaceboFTC/RPV/TDF plus FTC/RPV/TAF placebo for at least 96 weeks.
FTC/RPV/TAFFTC/RPV/TAFFTC/RPV/TAF plus FTC/RPV/TDF placebo for at least 96 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 48

The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the US FDA-defined snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 96

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 48

The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Change From Baseline in CD4+ Cell Count at Week 96Baseline; Week 96
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 96

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Change From Baseline in CD4+ Cell Count at Week 48Baseline; Week 48
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48Baseline; Week 48

Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.

Percent Change From Baseline in Hip BMD at Week 96Baseline; Week 96

Hip BMD was assessed by DXA scan.

Percent Change From Baseline in Spine BMD at Week 96Baseline; Week 96

Spine BMD was assessed by DXA scan.

Percent Change From Baseline in Spine BMD at Week 48Baseline; Week 48

Spine BMD was assessed by DXA scan.

Trial Locations

Locations (113)

University Health Network

🇨🇦

Toronto, Ontario, Canada

AHF Research Center

🇺🇸

Beverly Hills, California, United States

Pacific Oaks Medical Group

🇺🇸

Beverly Hills, California, United States

Long Beach Education and Research Consultants

🇺🇸

Long Beach, California, United States

Southern California Men's Medical Group

🇺🇸

Los Angeles, California, United States

Tarrant County ID Associates

🇺🇸

Los Angeles, California, United States

Alameda County Medical Center

🇺🇸

Oakland, California, United States

Desert Medical Group Inc., dba Desert Oasis Healthcare Medical Group

🇺🇸

Palm Springs, California, United States

Los Angeles BioMedical Institute at Harbor-UCLA Medical Center

🇺🇸

Torrance, California, United States

World Health Clinicians' CIRCLE CARE Center

🇺🇸

Norwalk, Connecticut, United States

Dupont Circle Physicians Group

🇺🇸

Washington, District of Columbia, United States

Capital Medical Associates, P.C.

🇺🇸

Washington, District of Columbia, United States

Whitman Walker Clinic

🇺🇸

Washington, District of Columbia, United States

Medical Faculty Associates

🇺🇸

Washington, District of Columbia, United States

Gary Richmond, MD, PA, Inc.

🇺🇸

Fort Lauderdale, Florida, United States

Therafirst Medical Centers

🇺🇸

Fort Lauderdale, Florida, United States

Midway Immunology & Research Center, LLC

🇺🇸

Fort Pierce, Florida, United States

Infectious Diseases Associates of NW Florida, P.A.

🇺🇸

Pensacola, Florida, United States

AIDS Research & Treatment Center of the Treasure Coast

🇺🇸

Vero Beach, Florida, United States

Triple O Research Institute, P.A.

🇺🇸

West Palm Beach, Florida, United States

Rowan Tree Medical PA

🇺🇸

Wilton Manors, Florida, United States

AIDS Research Consortium of Atlanta

🇺🇸

Atlanta, Georgia, United States

Atlanta ID Group

🇺🇸

Atlanta, Georgia, United States

Infectious Disease Specialists of Atlanta

🇺🇸

Decatur, Georgia, United States

Chatham County Health Department

🇺🇸

Savannah, Georgia, United States

Indiana University Medical Center

🇺🇸

Indianapolis, Indiana, United States

Brigham and Women's

🇺🇸

Boston, Massachusetts, United States

Community Research Initiative

🇺🇸

Boston, Massachusetts, United States

MetroWest Medical Center

🇺🇸

Framingham, Massachusetts, United States

Baystate Infectious Diseases Clinical Research

🇺🇸

Springfield, Massachusetts, United States

The Research Institute

🇺🇸

Springfield, Massachusetts, United States

Southampton Healthcare, Inc.

🇺🇸

Saint Louis, Missouri, United States

Saint Michael's Medical Center

🇺🇸

Newark, New Jersey, United States

Southwest CARE Center

🇺🇸

Santa Fe, New Mexico, United States

Upstate Infectious Diseases Associates

🇺🇸

Albany, New York, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

Carolinas Medical Center--Myers Park Infectious Disease Clinic

🇺🇸

Charlotte, North Carolina, United States

Rosedale Infectious Diseases

🇺🇸

Huntersville, North Carolina, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

North Texas Infectious Diseases Consultants

🇺🇸

Dallas, Texas, United States

Trinity Health and Wellness Center/AIDS Arms, Inc.

🇺🇸

Dallas, Texas, United States

AIDS Arms, Inc./Trinity Health & Wellness Center

🇺🇸

Fort Worth, Texas, United States

Research Access Network

🇺🇸

Houston, Texas, United States

Gordon E. Crofoot, MD, PA

🇺🇸

Houston, Texas, United States

DCOL Center for Clinical Research

🇺🇸

Longview, Texas, United States

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

🇺🇸

Annandale, Virginia, United States

Peter Shalit, MD

🇺🇸

Seattle, Washington, United States

Premier Clinical Research

🇺🇸

Spokane, Washington, United States

CHU Saint-Pierre University Hospital

🇧🇪

Brussels, Belgium

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

Maple Leaf Research

🇨🇦

Toronto, Ontario, Canada

Spectrum Health

🇨🇦

Vancouver, British Columbia, Canada

Clinique medicale l'Actuel

🇨🇦

Montreal, Quebec, Canada

University of Bonn

🇩🇪

Bonn, Germany

Hôpital Gui de Chauliac - Service Maladies Infectieuses et Tropicales

🇫🇷

Montpellier, France

Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH (zibp)

🇩🇪

Berlin, Germany

Center for HIV and Hepatogastroenterology

🇩🇪

Düsseldorf, Germany

Asklepios Klinik

🇩🇪

Hamburg, Germany

Universitätsklinikum Essen

🇩🇪

Essen, Germany

ICH Study Center Hamburg

🇩🇪

Hamburg, Germany

Infektiologikum

🇩🇪

Frankfurt, Germany

Universitat zu Koln

🇩🇪

Koln, Germany

Universitatsklinikum Hamburg-Eppendorf

🇩🇪

Hamburg, Germany

MUC Research GmbH

🇩🇪

München, Germany

Azienda Ospedaliera Papa Giovanni XXIII

🇮🇹

Bergamo, Italy

Clinical Research Puerto Rico Inc

🇵🇷

San Juan, Puerto Rico

Hospital del Mar

🇪🇸

Barcelona, Spain

Hospital General Universitario de Alicante

🇪🇸

Alicante, Spain

Hospital Germans Trias i Pujol

🇪🇸

Badalona, Spain

Hospital Universitary de Bellvitge

🇪🇸

Barcelona, Spain

Hospital Clínico Universitario San Carlos

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Karolinska Institutet

🇸🇪

Stockholm, Sweden

University Hospital Basel

🇨🇭

Basel, Switzerland

NHS Greater Glasgow

🇬🇧

Glasgow, United Kingdom

Barts & The London NHS Trust

🇬🇧

London, United Kingdom

Chelsea & Westminster Hospital

🇬🇧

London, United Kingdom

The Royal Free Hampstead NHS Trust

🇬🇧

London, United Kingdom

Mortimer Market Centre

🇬🇧

London, United Kingdom

The Hathersage Integrated Contraception, Sexual Health and HIV Service

🇬🇧

Manchester, United Kingdom

La Playa Medical Group and Clinical Research

🇺🇸

San Diego, California, United States

Kaiser Permanente

🇺🇸

San Leandro, California, United States

Optimus Medical

🇺🇸

San Francisco, California, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Fondazione IRCCS San Raffaele del Monte Tabor

🇮🇹

Milano, Italy

The University of Alabama at Birmingham (UAB)

🇺🇸

Birmingham, Alabama, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Apex Research Institute

🇺🇸

Denver, Colorado, United States

Hillsborough County Health Dept.

🇺🇸

Tampa, Florida, United States

St. Joseph's Comprehensive Research Institute

🇺🇸

Tampa, Florida, United States

University of Colorado

🇺🇸

Aurora, Colorado, United States

Infectious Disease Research Institute Inc.

🇺🇸

Tampa, Florida, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Spectrum Medical Group

🇺🇸

Phoenix, Arizona, United States

University Hospital Gent

🇧🇪

Ghent, Belgium

Cliniques Universitaires UCL Saint-Luc

🇧🇪

Brussels, Belgium

Be Well Medical Center

🇺🇸

Berkley, Michigan, United States

Jersey Shore Medical Center

🇺🇸

Neptune, New Jersey, United States

McGill University Health Centre

🇨🇦

Montreal, Quebec, Canada

Hope Clinical Research

🇵🇷

San Juan, Puerto Rico

South Jersey Infectious Disease

🇺🇸

Somers Point, New Jersey, United States

Clinique OPUS

🇨🇦

Montreal, Quebec, Canada

Geneva University Hospital

🇨🇭

Genève, Switzerland

Erasmus MC

🇳🇱

Rotterdam, Netherlands

University of California-UC Davis

🇺🇸

Sacramento, California, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

Orlando Immunology Center

🇺🇸

Orlando, Florida, United States

Central Texas Clinical Research

🇺🇸

Austin, Texas, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

AIDS Healthcare Foundation

🇺🇸

Miami, Florida, United States

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