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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01968551
First received: September 26, 2013
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

This open-label, multicenter study is to evaluate switching from optimized antiretroviral (ARV) regimens to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) plus darunavir (DRV) relative to current antiretroviral regimens (ARV), and to evaluate the efficacy, safety, and tolerability of the E/C/F/TAF STR+DRV in virologically suppressed, HIV-1 positive participants.

  • Cohort 1: 20 participants will receive E/C/F/TAF STR+DRV once daily. At Week 4, safety and efficacy data from the 20 subjects in Cohort 1 will be reviewed prior to randomizing additional subjects in Cohort 2. Cohort 1 subjects will continue treatment with E/C/F/TAF plus DRV for a total of 48 weeks.
  • Cohort 2: 150 participants will be randomized in a 2:1 ratio to receive E/C/F/TAF STR+DRV once daily, or remain on their current, pre-existing, ARV regimen.

Condition Intervention Phase
HIV-1
HIV Infections
Acquired Immunodeficiency Syndrome
Drug: E/C/F/TAF
Drug: DRV
Drug: Pre-existing ARV regimen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of subjects in each treatment arm in Cohort 2 with HIV-1 RNA < 50 copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects in each treatment arm in Cohort 2 with HIV-1 RNA < 50 copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: September 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Participants will receive E/C/F/TAF STR+DRV once daily with food for 48 weeks.
Drug: E/C/F/TAF
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regimen (STR) administered orally once daily
Drug: DRV
Darunavir (DRV) 800 mg administered orally once daily
Experimental: Cohort 2, Treatment Arm 1
Participants will be randomized to receive E/C/F/TAF STR+DRV once daily with food for 48 weeks.
Drug: E/C/F/TAF
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regimen (STR) administered orally once daily
Drug: DRV
Darunavir (DRV) 800 mg administered orally once daily
Active Comparator: Cohort 2, Treatment Arm 2
Participants will be randomized to continue on their current, pre-existing ARV regimen for 48 weeks.
Drug: Pre-existing ARV regimen
Participants will take their preexisting ARV regimen as prescribed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 available documentation of genotype/phenotype within 12 months prior to current regimen which must shows 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/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL)
  • Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
  • A female subject 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 study drug dosing.
    • Female subjects 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.
  • Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
  • Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Exclusion Criteria:

  • 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
  • Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study.
  • Must not have Q151M, T69ins, or > 3 TAMS present on documented historic genotype report
  • Subjects 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 subject 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 subject 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
  • Subjects receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir, cobicistat, emtricitabine, TAF, or DRV; or subjects with any known allergies to the study drugs.
  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: NCT01968551

  Hide Study Locations
Locations
United States, Arizona
Pueblo Family Physicians, Ltd.
Phoenix, Arizona, United States, 85015
Spectrum Medical Group
Phoenix, Arizona, United States, 85012
United States, California
Pacific Oaks Medical Group
Beverly Hills, California, United States, 90211
Kaiser Permanente
Hayward, California, United States, 94545
Long Beach Education and Research Consultants
Long Beach, California, United States, 90813
Anthony Mills MD Inc
Los Angeles, California, United States, 90069
Peter J Ruane, MD, Inc.
Los Angeles, California, United States, 90036
Kaiser Permanente Medical Group
Sacramento, California, United States, 95825
Kaiser San Francisco Division of Research
San Francisco, California, United States, 94118
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Whitman-Walker Health
Washington, District of Columbia, United States, 20009
Dupont Circle Physician's Group
Washington, District of Columbia, United States, 20009
United States, Florida
Midland Florida Clinical Research Center, LLC
DeLand, Florida, United States, 32720
Gary J.Richmond, MD, P.A.
Fort Lauderdale, Florida, United States, 33316
Therafirst Medical Center
Fort Lauderdale, Florida, United States, 33308
Midway Immunology and Research Center
Fort Pierce, Florida, United States, 34982
The Kinder Medical Group
Miami, Florida, United States, 33133
Orlando Immunology Center
Orlando, Florida, United States, 32803
Valuhealthmd/Idocf
Orlando, Florida, United States, 32806
Infectious Diseases Associates of NW FL
Pensacola, Florida, United States, 32504
Hillsborough County Health Department
Tampa, Florida, United States, 33602
St. Joseph's Comprehensive Research Institute
Tampa, Florida, United States, 33614
AIDS Research and Treatment Center of the Treasure Coast
Vero Beach, Florida, United States, 32960
Triple O Research Institute PA
West Palm Beach, Florida, United States, 33401
Rowan Tree Medical, P.A.
Wilton Manors, Florida, United States, 33305
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30312
Atlanta ID Group
Atlanta, Georgia, United States, 30309
Emory University HIV/AIDS Clinical Trials Unt
Atlanta, Georgia, United States, 30308
Mercer University, Mercer Medicine
Macon, Georgia, United States, 31201
United States, Illinois
Howard Brown Health Center
Chicago, Illinois, United States, 60613
The Ruth M. Rothstein CORE Center
Chicago, Illinois, United States, 60612
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Harvard Medical School
Boston, Massachusetts, United States, 02215
Baystate Infectious Diseases Clinical Research
Springfield, Massachusetts, United States, 01199
The Research Institute
Springfield, Massachusetts, United States, 01105
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Minnesota
Abbott Northwestern Hospital
Minneapolis, Minnesota, United States, 55404
United States, Missouri
The Kansas City Free Health Clinic/ KC Care Clinic
Kansas City, Missouri, United States, 64111
Southampton Healthcare, Inc.
Saint Louis, Missouri, United States, 63139
Central West Clinical Research
St. Louis, Missouri, United States, 63108
Washington University School of Medicine: ACTU
St. Louis, Missouri, United States, 63110
United States, Nevada
Nevada AIDS Research & Education Society
Las Vegas, Nevada, United States, 89102
United States, New Jersey
Saint Michaels Medical Center
Newark, New Jersey, United States, 07102
New Jersey Medical School
Newark, New Jersey, United States, 07103
South Jersey Infectious Disease
Somers Point, New Jersey, United States, 08244
United States, New Mexico
Southwest CARE Center
Santa Fe, New Mexico, United States, 87505
United States, New York
Albany Medical College
Albany, New York, United States, 12208
New York Hospital Queens
Flushing, New York, United States, 11355
Beth Israel Medical Center
New York, New York, United States, 10003
Weill Medical College
New York, New York, United States, 10011
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Carolinas Medical Center--Myer's Park
Charlotte, North Carolina, United States, 28207
Duke University Health System
Durham, North Carolina, United States, 27710
East Carolina University The Brody School of Medicine, Infectious Diseases
Greenville, North Carolina, United States, 27858
Rosedale Infectious Diseases
Huntersville, North Carolina, United States, 28078
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Summa Health System CARE Center
Akron, Ohio, United States, 44304
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
United States, Rhode Island
The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, South Carolina
University of South Carolina (USC) - Infectious Diseases Clinic
Columbia, South Carolina, United States, 29203
United States, Texas
Trinity Health & Wellness Center
Dallas, Texas, United States, 75208
North Texas infectious Diseases Consultants, PA
Dallas, Texas, United States, 75246
Gordon E. Crofoot MD PA
Houston, Texas, United States, 77098
Research Access Network
Houston, Texas, United States, 77098
Therapeutic Concepts, PA
Houston, Texas, United States, 77004
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
DCOL Center for Clinical Research
Longview, Texas, United States, 75606
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84102
United States, Virginia
Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)
Annandale, Virginia, United States, 220003
United States, Washington
Peter Shalit, MD
Seattle, Washington, United States, 98104
Canada, Alberta
Southern Alberta Clinic
Calgary, Alberta, Canada, T2R 0X7
Canada, British Columbia
Vancouver ID Research & Care Centre Society
Vancouver, British Columbia, Canada, V6Z2C7
Canada, Manitoba
Wrha - Health Sciences Centre Winnipeg
Winnipeg, Manitoba, Canada, R3A 1R9
Canada, Ontario
Ottawa Hospital - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Maple Leaf Research
Toronto, Ontario, Canada, M5G1K2
Canada, Quebec
Clinique médicale L'actuel
Montreal, Quebec, Canada, H2l 4P9
Clinique OPUS Inc.
Montreal, Quebec, Canada, H3A1T1
Reseach Institute of the MUHC
Montreal, Quebec, Canada, H2X 2P4
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Moupali Das, MD, MPH Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01968551     History of Changes
Other Study ID Numbers: GS-US-292-0119
Study First Received: September 26, 2013
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV-1
HIV
Treatment-Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Darunavir
Emtricitabine
Tenofovir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014