Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults

A Phase 3b, Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Cobicistat-boosted Darunavir Plus Two Fully Active Nucleoside Reverse Transcriptase Inhibitors in HIV-1 Infected, Antiretroviral Treatment-Naïve and -Experienced Adults With No Darunavir Resistance-associated Mutations

This study is to evaluate the safety and tolerability of cobicistat-boosted darunavir plus two fully active nucleoside analogue reverse transcriptase inhibitors in HIV 1 infected, antiretroviral treatment-naive and treatment-experienced adults with no darunavir (DRV) resistance-associated mutations.

After the Week 48 Visit, participants will be given the option to participate in an open-label rollover phase to receive cobicistat and attend visits every 12 weeks until it becomes commercially available, or until Gilead Sciences elects to terminate development of cobicistat.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome
• Intervention / Treatment: Drug: COBI; Drug: DRV; Drug: NRTIs

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • California
    • Long Beach, California, United States, 90813
      • Long Beach Education and Research Consultants, PC
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD Inc
    • Los Angeles, California, United States, 90036
      • Peter J Ruane MD Inc.
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Group
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
    • San Francisco, California, United States, 94109
      • Metropolis Medical
  • Colorado
    • Denver, Colorado, United States, 80220
      • Apex Research LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physician's Group
    • Washington, District of Columbia, United States, 20009
      • Whitman-Walker Health
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond,M.D., P.A.
    • Fort Pierce, Florida, United States, 34983
      • Midway Immunology and Research Center
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Tampa, Florida, United States, 33614
      • St. Joseph's Comprehensive Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta ID Group
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31220
      • Mercer University
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • Hawaii Center for AIDS, University of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
    • Chicago, Illinois, United States, 60657
      • Northstar Medical Center
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative of New England
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • St. Louis, Michigan, United States, 63108
      • Central West Clinical Research Inc
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • HIV Program Hennepin County Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital / Division of Infectious Diseases
    • Mt. Vernon, New York, United States, 10550
      • Greiger Clinic
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28079
      • Carolinas Medical Center-Myer's Park Infectious Disease Clinic
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Services
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
    • Philadelphia, Pennsylvania, United States, 19104
      • University of PA
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75208
      • Trinity Health and Wellness Center/AIDS Arms, Inc.
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Clinical Research, Inc.
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Gordon Crofoot MD, PA
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
  • Washington
    • Seattle, Washington, United States, 89104
      • Swedish Medical Center

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

Inclusion Criteria:

• Adult ≥ 18 years males or non-pregnant females
• Ability to understand and sign a written informed consent form
• General medical condition that does not interfere with the assessments and the completion of the trial
• Treatment Naive: No prior use of any approved or investigational antiretroviral drug for any length of time OR
• Treatment Experienced: Stable antiretroviral regimen for at least 12 weeks prior to screening
• Plasma HIV-1 RNA levels ≥ 1000 copies/mL at Screening
• Screening genotype report shows full sensitivity to two nucleoside analogue reverse transcriptase inhibitors (NRTIs) and no darunavir resistance-associated mutations
• Normal electrocardiogram (ECG)
• Hepatic transaminases ≤ 2.5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL
• Adequate hematologic function
• Serum amylase ≤ 2 × ULN and serum lipase ≤ 3 × ULN
• Adequate renal function: Estimated glomerular filtration rate ≥ 80 mL/min
• Females of childbearing potential must agree to utilize protocol-recommended methods of contraception, or be nonheterosexually active, practice sexual abstinence or have a vasectomized partner from Screening throughout the duration of the study period and for 30 days following the last dose of study drug.
• Male subjects must agree to utilize protocol-recommended methods of contraception during heterosexual intercourse from the Screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product or be nonheterosexually active, practice sexual abstinence, or be vasectomized.

Exclusion Criteria:

• Previous or current use of darunavir
• A new AIDS-defining condition diagnosed within the 30 days prior to Screening
• Females who are breastfeeding
• Positive serum pregnancy test (if female of childbearing potential)
• Proven or suspected acute hepatitis in the 30 days prior to study entry
• Subjects receiving drug treatment for hepatitis C virus (HCV), or subjects who are anticipated to receive treatment for HCV during the course of the study
• Have a history of ongoing active liver disease or experiencing decompensated cirrhosis irrespective of liver enzyme levels
• 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
• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Participation in any other clinical trial
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements.
• Subjects receiving ongoing therapy with any of the medications, including drugs not to be used with cobicistat, darunavir, or investigator selected NRTIs; or subjects with any known allergies to cobicistat tablets, darunavir tablets or contraindications for the 2 NRTIs as part of the regimen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: COBI-boosted DRV; Participants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase.

Drug: COBI; 150 mg tablet administered orally with food once daily; Other Names: Tybost®; GS-9350; Drug: DRV; 800 mg (2 x 400 mg tablets) administered orally with food once daily; Other Names: TMC114; Prezista®; Drug: NRTIs; Participants will receive 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) selected by the investigator after resistance testing at screening and administered according to prescribing information. NRTIs may include emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), zidovudine+FTC/TDF, abacavir (ABC)+TDF, ABC+FTC/TDF, ABC+lamivudine (3TC), or didanosine (DDI)+FTC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	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 Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis)	Week 24
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis)	Week 48
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 24	Up to 24 weeks
Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 48	Up to 48 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 23, 2011
• First Posted (Estimate): September 26, 2011

Study Record Updates

• Last Update Posted (Estimate): December 14, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment Experienced; Treatment Naïve
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Cobicistat; Darunavir
• Other Study ID Numbers: GS-US-216-0130; 2011-003501-22 (EudraCT Number)