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
- Conditions
- HIV-1 Infection
- Interventions
- Registration Number
- NCT02345226
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 881
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FTC/RPV/TAF EFV/FTC/TDF Placebo FTC/RPV/TAF plus EFV/FTC/TDF placebo for at least 96 weeks. FTC/RPV/TAF FTC/RPV/TAF FTC/RPV/TAF plus EFV/FTC/TDF placebo for at least 96 weeks. EFV/FTC/TDF EFV/FTC/TDF EFV/FTC/TDF plus FTC/RPV/TAF placebo for at least 96 weeks. EFV/FTC/TDF FTC/RPV/TAF Placebo EFV/FTC/TDF plus FTC/RPV/TAF placebo for at least 96 weeks. Open Label Extension Phase FTC/RPV/TAF 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm 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
Name Time Method Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm 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 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.
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 Baseline; Week 48 Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Change From Baseline in CD4+ Cell Count at Week 96 Baseline; Week 96 Percent Change From Baseline in Spine BMD at Week 48 Baseline; Week 48 Spine BMD was assessed by DXA scan.
Change From Baseline in CD4+ Cell Count at Week 48 Baseline; Week 48 Percent Change From Baseline in Spine BMD at Week 96 Baseline; Week 96 Spine BMD was assessed by DXA scan.
Change From Baseline in HIVSI Score at Week 96 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.
Percent Change From Baseline in Hip BMD at Week 96 Baseline; Week 96 Hip BMD was assessed by DXA scan.
Change From Baseline in HIV Symptoms Index Score (HIVSI) at Week 48 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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot 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.
Trial Locations
- Locations (113)
Brigham and Women's
🇺🇸Boston, Massachusetts, United States
Southern California Men's Medical Group
🇺🇸Los Angeles, California, United States
Tarrant County ID Associates
🇺🇸Los Angeles, California, United States
Infectious Diseases Associates of NW Florida, P.A.
🇺🇸Pensacola, Florida, United States
Rowan Tree Medical PA
🇺🇸Wilton Manors, Florida, United States
Atlanta ID Group
🇺🇸Atlanta, Georgia, United States
Mercer University School of Medicine
🇺🇸Macon, Georgia, United States
Chatham County Health Department
🇺🇸Savannah, Georgia, United States
The CORE Foundation
🇺🇸Chicago, Illinois, United States
Baystate Infectious Diseases Clinical Research
🇺🇸Springfield, Massachusetts, United States
Southampton Healthcare, Inc.
🇺🇸Saint Louis, Missouri, United States
Southwest CARE Center
🇺🇸Santa Fe, New Mexico, United States
The Brody School of Medicine
🇺🇸Greenville, North Carolina, United States
Rosedale Infectious Diseases
🇺🇸Huntersville, North Carolina, United States
Clinique medicale l'Actuel
🇨🇦Montreal, Quebec, Canada
Hopital Saint Louis
🇫🇷Paris, France
Chu Tours
🇫🇷Tours, France
Hope Clinical Research
🇵🇷San Juan, Puerto Rico
King's College Hospital
🇬🇧London, United Kingdom
Barts & The London NHS Trust
🇬🇧London, United Kingdom
Peter Shalit, MD
🇺🇸Seattle, Washington, United States
La Playa Medical Group and Clinical Research
🇺🇸San Diego, California, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
Kaiser Permanente
🇺🇸San Leandro, California, United States
Optimus Medical
🇺🇸San Francisco, California, United States
Health Sciences Centre
🇨🇦Winnipeg, Manitoba, Canada
The Ohio State University
🇺🇸Columbus, Ohio, United States
Spectrum Health
🇨🇦Vancouver, British Columbia, Canada
University Hospital Basel
🇨🇭Basel, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Medical Faculty Associates, Inc.
🇺🇸Washington, District of Columbia, United States
Capital Medical Associates, P.C.
🇺🇸Washington, District of Columbia, United States
Geneva University Hospital
🇨🇭Genève, Switzerland
Jacobi Medical Center
🇺🇸Bronx, New York, United States
University of Alberta
🇨🇦Edmonton, Alberta, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
South Jersey Infectious Disease
🇺🇸Somers Point, New Jersey, United States
Maricopa Integrated Health System
🇺🇸Phoenix, Arizona, United States
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Apex Research Institute
🇺🇸Denver, Colorado, United States
Hospital Universitary de Bellvitge
🇪🇸Barcelona, Spain
University of Colorado
🇺🇸Aurora, Colorado, 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
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
AHF Research Center
🇺🇸Beverly Hills, California, United States
Long Beach Education and Research Consultants
🇺🇸Long Beach, 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
Whitman Walker Clinic
🇺🇸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
University of Miami
🇺🇸Miami, Florida, United States
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Infectious Disease Specialists of Atlanta
🇺🇸Decatur, Georgia, United States
MetroWest Medical Center
🇺🇸Framingham, Massachusetts, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
The Research Institute
🇺🇸Springfield, Massachusetts, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
Upstate Infectious Diseases Associates
🇺🇸Albany, 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
Infectious Disease Consultants, PA
🇺🇸Charlotte, North Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Southwest Infectious Disease Clinical Research, Inc.
🇺🇸Dallas, Texas, United States
Central Texas Clinical Research
🇺🇸Austin, 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
CHU Saint-Pierre University Hospital
🇧🇪Brussels, Belgium
Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
🇺🇸Annandale, Virginia, United States
Cliniques Universitaires UCL Saint-Luc
🇧🇪Brussels, Belgium
Premier Clinical Research
🇺🇸Spokane, Washington, United States
Maple Leaf Research
🇨🇦Toronto, Ontario, Canada
Clinique OPUS
🇨🇦Montreal, Quebec, Canada
University Health Network
🇨🇦Toronto, Ontario, Canada
Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH (zibp)
🇩🇪Berlin, Germany
University of Bonn
🇩🇪Bonn, Germany
Center for HIV and Hepatogastroenterology
🇩🇪Duesseldorf, Germany
Infektiologikum
🇩🇪Frankfurt, Germany
Universitat zu Koln
🇩🇪Koln, Germany
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Essen
🇩🇪Essen, Germany
ICH Study Center Hamburg
🇩🇪Hamburg, Germany
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Clinical Research Puerto Rico Inc
🇵🇷San Juan, Puerto Rico
MUC Research GmbH
🇩🇪München, Germany
University of Puerto Rico School of Medicine
🇵🇷San Juan, Puerto Rico
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
The Royal Free Hampstead NHS Trust
🇬🇧London, United Kingdom
Mortimer Market Centre
🇬🇧London, United Kingdom
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Research Access Network
🇺🇸Houston, Texas, United States
North Texas Infectious Diseases Consultants
🇺🇸Dallas, Texas, United States
AIDS Research & Treatment Center of the Treasure Coast
🇺🇸Vero Beach, Florida, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
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
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Hopital Bichat Claude Bernard
🇫🇷Paris, France
Montefiore Medical Center
🇺🇸Bronx, New York, United States
AIDS Healthcare Foundation
🇺🇸Miami, Florida, United States