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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome; HIV-1
• Intervention / Treatment: Drug: E/C/F/TAF; Drug: DRV; Drug: Baseline DRV- containing ARV regimen

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R 0X7
      • Southern Alberta Clinic
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z2C7
      • Vancouver ID Research & Care Centre Society
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Wrha - Health Sciences Centre Winnipeg
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G1K2
      • Maple Leaf Research
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • Clinique Médicale L'Actuel
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Pueblo Family Physicians, Ltd.
  • California
    • Beverly Hills, California, United States, 90211
      • Pacific Oaks Medical Group
    • Hayward, California, United States, 94545
      • Kaiser Permanente
    • Long Beach, California, United States, 90813
      • Long Beach Education and Research Consultants
    • Los Angeles, California, United States, 90036
      • Peter J Ruane, MD, Inc.
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Group
    • San Francisco, California, United States, 94118
      • Kaiser San Francisco Division of Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physician's Group
  • Florida
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research Center, LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Therafirst Medical Center
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J.Richmond, MD, P.A.
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • Valuhealthmd/Idocf
    • Pensacola, Florida, United States, 32504
      • Infectious Diseases Associates of NW FL
    • Tampa, Florida, United States, 33602
      • Hillsborough County Health Department
    • Tampa, Florida, United States, 33614
      • St. Joseph's Comprehensive Research Institute
    • Vero Beach, Florida, United States, 32960
      • AIDS Research and Treatment Center of the Treasure Coast
    • West Palm Beach, Florida, United States, 33401
      • Triple O Research Institute PA
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Atlanta, Georgia, United States, 30312
      • AIDS Research Consortium of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University, Mercer Medicine
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Chicago, Illinois, United States, 60612
      • The Ruth M. Rothstein CORE Center
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Harvard Medical School
    • Springfield, Massachusetts, United States, 01199
      • Baystate Infectious Diseases Clinical Research
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Abbott Northwestern Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • The Kansas City Free Health Clinic/ KC Care Clinic
    • Saint Louis, Missouri, United States, 63108
      • Central West Clinical Research
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Flushing, New York, United States, 11355
      • New York Hospital Queens
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10011
      • Weill Medical College
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center--Myer's Park
    • Durham, North Carolina, United States, 27710
      • Duke University Health System
    • Greenville, North Carolina, United States, 27858
      • East Carolina University The Brody School of Medicine, Infectious Diseases
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System CARE Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants, PA
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
    • Longview, Texas, United States, 75606
      • DCOL Center for Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • University of Utah
  • Virginia
    • Annandale, Virginia, United States, 220003
      • Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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 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.
• Male individuals 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 individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Key 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
• 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants 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.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya®; Drug: DRV; 800 mg tablet administered orally once daily
Experimental: Cohort 2, Treatment Group 1; Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya®; Drug: DRV; 800 mg tablet administered orally once daily
Active Comparator: Cohort 2, Treatment Group 2; Participants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks.	Drug: Baseline DRV- containing ARV regimen; Participants will take their baseline DRV- containing ARV regimen as prescribed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24
Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at 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.	Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.
• Greg 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2013
• Primary Completion (Actual): July 21, 2015
• Study Completion (Actual): July 9, 2016

Study Registration Dates

• First Submitted: September 26, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimate): October 24, 2013

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment-Experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: GS-US-292-0119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No