Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Gilead Sciences


Information provided by (Responsible Party)
Gilead Sciences
ClinicalTrials.gov Identifier
NCT02345226

First received: January 19, 2015
Last updated: December 16, 2019
Last Verified: December 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV-1 Infection

Drug : FTC/RPV/TAF
Drug : EFV/FTC/TDF Placebo
Drug : EFV/FTC/TDF
Drug : FTC/RPV/TAF Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3b, Randomized, Double-Blind 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 Subjects

Further study details as provided by Gilead Sciences:

Primary Outcome Measures

  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 48 ]
    The percentage of participants achieving 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.
Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 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.
  • Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 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 96 as Defined by the US FDA-defined Snapshot [ Time Frame: Week 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 48 [ Time Frame: Baseline; Week 48 ]
  • Change From Baseline in CD4+ Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]
  • Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 [ Time Frame: Baseline; Week 48 ]
    Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
  • Percent Change From Baseline in Hip BMD at Week 96 [ Time Frame: Baseline; Week 96 ]
    Hip BMD was assessed by DXA scan.
  • Percent Change From Baseline in Spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ]
    Spine BMD was assessed by DXA scan.
  • Percent Change From Baseline in Spine BMD at Week 96 [ Time Frame: Baseline; Week 96 ]
    Spine BMD was assessed by DXA scan.
  • Change From Baseline in HIV Symptoms Index Score (HIVSI) at Week 48 [ Time Frame: Baseline; Week 48 ]
    The HIV Symptoms Index was a 20-item, self-reported measure that addressed presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Twenty HIV symptoms including Fatigue, Fever, Dizziness, Hand/Foot Pain, Memory Loss, Nausea, Diarrhea, Sadness, Nervous/anxious, Sleep Trouble, Skin Problems, Cough, Headache, Appetite Loss, Stomach Pain, Muscle/Joint Pain, Sex Problems, Change in Fat Deposits, Weight Loss, and Hair Loss were assessed. There were 5 possible responses (0 = I don't have this symptom; 1 = It doesn't bother me; 2 = It bothers me a little; 3 = It bothers me; and 4 = It bothers me a lot) for each HIV symptom. Total HIV Symptoms Index Score was derived from all 20 HIV symptoms by counting the number of bothersome symptoms. Total score would be missing if any of the individual items were missing.
  • Change From Baseline in HIVSI Score at Week 96 [ Time Frame: Baseline; Week 96 ]
    The HIV Symptoms Index was a 20-item, self-reported measure that addressed presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Twenty HIV symptoms including Fatigue, Fever, Dizziness, Hand/Foot Pain, Memory Loss, Nausea, Diarrhea, Sadness, Nervous/anxious, Sleep Trouble, Skin Problems, Cough, Headache, Appetite Loss, Stomach Pain, Muscle/Joint Pain, Sex Problems, Change in Fat Deposits, Weight Loss, and Hair Loss were assessed. There were 5 possible responses (0 = I don't have this symptom; 1 = It doesn't bother me; 2 = It bothers me a little; 3 = It bothers me; and 4 = It bothers me a lot) for each HIV symptom. Total HIV Symptoms Index Score was derived from all 20 HIV symptoms by counting the number of bothersome symptoms. Total score would be missing if any of the individual items were missing.

Enrollment: 881
Study Start Date: January 26, 2015
Study Completion Date: January 2, 2019
Primary Completion Date: June 29, 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: FTC/RPV/TAF
FTC/RPV/TAF plus EFV/FTC/TDF placebo for at least 96 weeks.
Drug: FTC/RPV/TAF

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

Other Name: Odefsey®
Drug: EFV/FTC/TDF Placebo

Tablets administered orally once daily

Active Comparator: EFV/FTC/TDF
EFV/FTC/TDF plus FTC/RPV/TAF placebo for at least 96 weeks.
Drug: EFV/FTC/TDF

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

Other Name: Atripla®
Drug: FTC/RPV/TAF Placebo

Tablets administered orally once daily

Experimental: 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.
Drug: FTC/RPV/TAF

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

Other Name: Odefsey®
Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Key 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

  • 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 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
Note: Other protocol defined inclusion/exclusion criteria may apply.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02345226

Locations

United States, Arizona
Maricopa Integrated Health System
Phoenix, Arizona, United States, 85004
Spectrum Medical Group
Phoenix, Arizona, United States
United States, California
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
Kaiser Permanente
Los Angeles, California, United States
Southern California Men's Medical Group
Los Angeles, California, United States
Tarrant County ID Associates
Los Angeles, California, United States
Kaiser Permanente
Sacramento, California, United States
University of California-UC Davis
Sacramento, California, United States
La Playa Medical Group and Clinical Research
San Diego, California, United States
Kaiser Permanente
San Francisco, California, United States
Optimus Medical
San Francisco, California, United States
Kaiser Permanente
San Leandro, California, United States
Los Angeles BioMedical Institute at Harbor-UCLA Medical Center
Torrance, California, United States
United States, Colorado
University of Colorado
Aurora, Colorado, United States
Apex Research Institute
Denver, Colorado, United States
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States
World Health Clinicians' CIRCLE CARE Center
Norwalk, Connecticut, United States
United States, District of Columbia
Capital Medical Associates, P.C.
Washington, District of Columbia, United States
Medical Faculty Associates, Inc.
Washington, District of Columbia, United States
Whitman Walker Clinic
Washington, District of Columbia, United States
United States, Florida
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
AIDS Healthcare Foundation
Miami Beach, Florida, United States
AIDS Healthcare Foundation
Miami, Florida, United States
University of Miami
Miami, Florida, United States
Orlando Immunology Center
Orlando, Florida, United States
Infectious Diseases Associates of NW Florida, P.A.
Pensacola, Florida, United States
Hillsborough County Health Dept.
Tampa, Florida, United States
Infectious Disease Research Institute Inc.
Tampa, Florida, United States
St. Joseph's Comprehensive Research Institute
Tampa, 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
United States, Georgia
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
Mercer University School of Medicine
Macon, Georgia, United States
Chatham County Health Department
Savannah, Georgia, United States
United States, Illinois
The CORE Foundation
Chicago, Illinois, United States
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States
Brigham and Women's
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
United States, Michigan
Be Well Medical Center
Berkley, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States
United States, Missouri
Southampton Healthcare, Inc.
Saint Louis, Missouri, United States
United States, New Jersey
Saint Michael's Medical Center
Newark, New Jersey, United States
South Jersey Infectious Disease
Somers Point, New Jersey, United States
United States, New Mexico
Southwest CARE Center
Santa Fe, New Mexico, United States
United States, New York
Upstate Infectious Diseases Associates
Albany, New York, United States
Jacobi Medical Center
Bronx, New York, United States
Montefiore Medical Center
Bronx, New York, United States
North Shore University Hospital
Manhasset, New York, United States
Columbia University Medical Center/ New York Presbyterian
New York, New York, United States
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Infectious Disease Consultants, PA
Charlotte, North Carolina, United States
The Brody School of Medicine
Greenville, North Carolina, United States
Rosedale Infectious Diseases
Huntersville, North Carolina, United States
United States, Ohio
The Ohio State University
Columbus, Ohio, United States
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Rhode Island
The Miriam Hospital
Providence, Rhode Island, United States
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States
United States, Texas
Central Texas Clinical Research
Austin, Texas, United States
North Texas Infectious Diseases Consultants
Dallas, Texas, United States
Southwest Infectious Disease Clinical Research, Inc.
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
Gordon E. Crofoot, MD, PA
Houston, Texas, United States
Research Access Network
Houston, Texas, United States
DCOL Center for Clinical Research
Longview, Texas, United States
United States, Virginia
Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
Annandale, Virginia, United States
United States, Washington
Peter Shalit, MD
Seattle, Washington, United States
Premier Clinical Research
Spokane, Washington, United States
Belgium
CHU Saint-Pierre University Hospital
Brussels, Belgium
Cliniques Universitaires UCL Saint-Luc
Brussels, Belgium
Canada
University of Alberta
Edmonton, Alberta, Canada
Spectrum Health
Vancouver, British Columbia, Canada
Health Sciences Centre
Winnipeg, Manitoba, Canada
Maple Leaf Research
Toronto, Ontario, Canada
University Health Network
Toronto, Ontario, Canada
Clinique medicale l'Actuel
Montreal, Quebec, Canada
Clinique OPUS
Montreal, Quebec, Canada
McGill University Health Centre
Montreal, Quebec, Canada
France
Hopital Bichat Claude Bernard
Paris, France
Hopital Saint Louis
Paris, France
Chu Tours
Tours, France
Germany
Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH (zibp)
Berlin, Germany
University of Bonn
Bonn, Germany
Center for HIV and Hepatogastroenterology
Duesseldorf, Germany
Universitätsklinikum Essen
Essen, Germany
Infektiologikum
Frankfurt, Germany
ICH Study Center Hamburg
Hamburg, Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, Germany
Universitat zu Koln
Koln, Germany
MUC Research GmbH
München, Germany
Puerto Rico
Clinical Research Puerto Rico Inc
San Juan, Puerto Rico
Hope Clinical Research
San Juan, Puerto Rico
University of Puerto Rico School of Medicine
San Juan, Puerto Rico
Spain
Hospital General Universitario de Alicante
Alicante, Spain
Hospital Clinic i Provincial
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Universitary de Bellvitge
Barcelona, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Switzerland
University Hospital Basel
Basel, Switzerland
Geneva University Hospital
Genève, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
United Kingdom
Barts & The London NHS Trust
London, United Kingdom
King's College Hospital
London, United Kingdom
Mortimer Market Centre
London, United Kingdom
The Royal Free Hampstead NHS Trust
London, United Kingdom

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director Gilead Sciences
More Information

More Information


Responsible Party: Gilead Sciences  
ClinicalTrials.gov Identifier: NCT02345226   History of Changes  
Other Study ID Numbers: GS-US-366-1160  
  2014-004779-21  
Study First Received: January 19, 2015  
Last Updated: December 16, 2019  
Individual Participant Data    
Plan to Share IPD: Yes  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Gilead Sciences:

HIV

Additional relevant MeSH terms:
Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.