Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
A Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
1 other identifier
interventional
158
2 countries
62
Brief Summary
The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed dose combination (FDC) plus darunavir (DRV) relative to current antiretroviral regimens (ARV) in virologically suppressed, HIV-1 positive participants with HIV-1 RNA \<50 copies/mL at Week 24. This study consists of 48 weeks of open-label phase followed by an optional Extension Phase in which all the participants will receive E/C/F/TAF+DRV.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Sep 2013
Typical duration for phase_3
62 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 3, 2013
CompletedFirst Submitted
Initial submission to the registry
September 26, 2013
CompletedFirst Posted
Study publicly available on registry
October 24, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 21, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 9, 2016
CompletedResults Posted
Study results publicly available
November 1, 2016
CompletedNovember 16, 2018
July 1, 2017
1.9 years
September 26, 2013
July 20, 2016
October 19, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 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.
Week 24
Secondary Outcomes (3)
Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48
Week 48
Change From Baseline in CD4+ Cell Count at Week 24
Baseline; Week 24
Change From Baseline in CD4+ Cell Count at Week 48
Baseline; Week 48
Study Arms (3)
Cohort 1
EXPERIMENTALParticipants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks. Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.
Cohort 2, Treatment Group 1
EXPERIMENTALParticipants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.
Cohort 2, Treatment Group 2
ACTIVE COMPARATORParticipants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks.
Interventions
150/150/200/10 mg FDC tablet administered orally once daily
Participants will take their baseline DRV- containing ARV regimen as prescribed.
Eligibility Criteria
You may qualify if:
- Ability to understand and sign a written informed consent form
- History of at least two prior antiretroviral regimens, and history of resistance to at least two different classes of antiretroviral agents
- Plasma HIV-1 RNA levels \< 50 copies/mL at screening. Virologically suppressed on the current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once daily continuously for ≥ 4 months preceding the screening visit and have maintained documented undetectable plasma HIV-1 RNA levels (\< 50 copies/mL) and must have documentation of genotype/phenotype prior to current regimen which shows no darunavir associated resistance mutation.
- Currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but not twice daily), or have never received integrase inhibitor, or have documentation of genotype/phenotype within 12 months prior to current regimen which must show no evidence of resistance to integrase inhibitors
- Normal ECG
- Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance
- 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)
- A female individual is eligible to enter the study if it is confirmed that she is:
- Not pregnant or nursing
- Of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women \> 54 years of age with cessation (for ≥ 12 months) of previously occurring menses), or
- Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last study drug dose.
- Female individuals 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.
- +2 more criteria
You may not qualify if:
- A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4 cell count and/or percentage criteria)
- Hepatitis B surface antigen (HBsAg) positive
- Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study.
- Must not have Q151M, T69ins, or \> 3 thymidine analogue mutations (TAMS) present on documented historic genotype report
- Individuals experiencing decompensated cirrhosis
- Females who are breastfeeding
- Positive serum pregnancy test
- Have an implanted defibrillator or pacemaker
- Current alcohol or substance use that may interfere with individual's study 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, non-invasive cutaneous squamous carcinoma.
- Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 visit
- Any other clinical condition or prior therapy that 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, including drugs not to be used with elvitegravir, cobicistat, emtricitabine, TAF, or DRV; or individuals with any known allergies to the study drugs.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (62)
Pueblo Family Physicians, Ltd.
Phoenix, Arizona, 85015, United States
Pacific Oaks Medical Group
Beverly Hills, California, 90211, United States
Kaiser Permanente
Hayward, California, 94545, United States
Long Beach Education and Research Consultants
Long Beach, California, 90813, United States
Peter J Ruane, MD, Inc.
Los Angeles, California, 90036, United States
Kaiser Permanente Medical Group
Sacramento, California, 95825, United States
Kaiser San Francisco Division of Research
San Francisco, California, 94118, United States
Dupont Circle Physician's Group
Washington D.C., District of Columbia, 20009, United States
Midland Florida Clinical Research Center, LLC
DeLand, Florida, 32720, United States
Therafirst Medical Center
Fort Lauderdale, Florida, 33308, United States
Gary J.Richmond, MD, P.A.
Fort Lauderdale, Florida, 33316, United States
Midway Immunology and Research Center
Ft. Pierce, Florida, 34982, United States
Orlando Immunology Center
Orlando, Florida, 32803, United States
Valuhealthmd/Idocf
Orlando, Florida, 32806, United States
Infectious Diseases Associates of NW FL
Pensacola, Florida, 32504, United States
Hillsborough County Health Department
Tampa, Florida, 33602, United States
St. Joseph's Comprehensive Research Institute
Tampa, Florida, 33614, United States
AIDS Research and Treatment Center of the Treasure Coast
Vero Beach, Florida, 32960, United States
Triple O Research Institute PA
West Palm Beach, Florida, 33401, United States
Atlanta ID Group
Atlanta, Georgia, 30309, United States
AIDS Research Consortium of Atlanta
Atlanta, Georgia, 30312, United States
Mercer University, Mercer Medicine
Macon, Georgia, 31201, United States
The Ruth M. Rothstein CORE Center
Chicago, Illinois, 60612, United States
Howard Brown Health Center
Chicago, Illinois, 60613, United States
Johns Hopkins University
Lutherville, Maryland, 21093, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Harvard Medical School
Boston, Massachusetts, 02215, United States
Baystate Infectious Diseases Clinical Research
Springfield, Massachusetts, 01199, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55404, United States
The Kansas City Free Health Clinic/ KC Care Clinic
Kansas City, Missouri, 64111, United States
Central West Clinical Research
St Louis, Missouri, 63108, United States
South Jersey Infectious Disease
Somers Point, New Jersey, 08244, United States
Southwest CARE Center
Santa Fe, New Mexico, 87505, United States
Albany Medical College
Albany, New York, 12208, United States
New York Hospital Queens
Flushing, New York, 11355, United States
Beth Israel Medical Center
New York, New York, 10003, United States
Weill Medical College
New York, New York, 10011, United States
University of Rochester
Rochester, New York, 14642, United States
Carolinas Medical Center--Myer's Park
Charlotte, North Carolina, 28207, United States
Duke University Health System
Durham, North Carolina, 27710, United States
East Carolina University The Brody School of Medicine, Infectious Diseases
Greenville, North Carolina, 27858, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Summa Health System CARE Center
Akron, Ohio, 44304, United States
The Ohio State University Medical Center
Columbus, Ohio, 43210, United States
University Of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Philadelphia FIGHT
Philadelphia, Pennsylvania, 19107, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
The Miriam Hospital
Providence, Rhode Island, 02906, United States
North Texas infectious Diseases Consultants, PA
Dallas, Texas, 75246, United States
Therapeutic Concepts, PA
Houston, Texas, 77004, United States
Gordon E. Crofoot MD PA
Houston, Texas, 77098, United States
DCOL Center for Clinical Research
Longview, Texas, 75606, United States
University of Utah
Salt Lake City, Utah, 84102, United States
Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)
Annandale, Virginia, 220003, United States
Peter Shalit, MD
Seattle, Washington, 98104, United States
Southern Alberta Clinic
Calgary, Alberta, T2R 0X7, Canada
Vancouver ID Research & Care Centre Society
Vancouver, British Columbia, V6Z2C7, Canada
Wrha - Health Sciences Centre Winnipeg
Winnipeg, Manitoba, R3A 1R9, Canada
Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6, Canada
Maple Leaf Research
Toronto, Ontario, M5G1K2, Canada
Clinique médicale L'actuel
Montreal, Quebec, H2l 4P9, Canada
Related Publications (2)
Huhn GD, Tebas P, Gallant J, Wilkin T, Cheng A, Yan M, Zhong L, Callebaut C, Custodio JM, Fordyce MW, Das M, McCallister S. A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):193-200. doi: 10.1097/QAI.0000000000001193.
PMID: 27753684BACKGROUNDGreg Huhn, Pablo Tebas, Joel Gallant et al. Strategic Simplification: the Efficacy and Safety of Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Plus Darunavir (DRV) in Treatment-Experienced HIV-1-Infected Adults (NCT01968551). IDWeek; 2015 San Diego, CA Oct. 7-11.
BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 26, 2013
First Posted
October 24, 2013
Study Start
September 3, 2013
Primary Completion
July 21, 2015
Study Completion
July 9, 2016
Last Updated
November 16, 2018
Results First Posted
November 1, 2016
Record last verified: 2017-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 18 months after study completion
- Access Criteria
- A secured external environment with username, password, and RSA code.
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.