D/C/F/TAF Versus COBI-boosted DRV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment Naive Adults

A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Darunavir/Cobicistat/Emtricitabine/GS-7340 Single Tablet Regimen Versus Cobicistat-boosted Darunavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in HIV-1 Infected, Antiretroviral Treatment Naive Adults

This study is to evaluate the safety and efficacy darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus darunavir (DRV)+cobicistat (COBI)+emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in HIV-1 infected, antiretroviral treatment-naive adults as determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 24.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome
• Intervention / Treatment: Drug: FTC/TDF Placebo; Drug: D/C/F/TAF; Drug: DRV Placebo; Drug: COBI Placebo; Drug: DRV; Drug: COBI; Drug: FTC/TDF; Drug: D/C/F/TAF Placebo

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Research Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane, MD, Inc.
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD, Inc
    • Newport Beach, California, United States, 92663
      • Orange Coast Medical Group
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center, East Bay AIDS Center
    • 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, 94118
      • Kasier Permanente Medical Center
    • San Francisco, California, United States, 94118
      • TPMG--Clinical Trials Unit
  • Colorado
    • Denver, Colorado, United States, 80209
      • APEX Research
    • Denver, Colorado, United States, 80220
      • Denver Infectious Disease Consultants, PLLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physician's Group
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC
    • Washington, District of Columbia, United States, 20009
      • Whitman-Walker Health
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond,M.D.,P.A.
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • IDOCF/ValuhealthMD, LLC
    • Tampa, Florida, United States, 33614
      • St. Joseph's Comprehensive Research Institute
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University Mercer Medicine
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215
      • Community Research Initiative (CRI)
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63108
      • Central West Clinical Research Inc
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital / Division of Infectious Diseases
    • New York, New York, United States, 10011
      • Weill Cornell Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • ID Consultants, P.A.
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of South Carolina School of Medicine Division of Infectious Disease
  • Texas
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Clinical Research Inc
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot, MD., PA
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Virginia
    • Annandale, Virginia, United States, 22003
      • CARE-ID
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, M.D.

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 which does not interfere with the assessments and the completion of the trial
• Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
• CD4+ cell count > 50 cells/µL
• Treatment-naive: No prior use of any approved or experimental anti-HIV drug for any length of time
• Screening genotype report must show sensitivity to DRV, TDF and FTC
• Normal ECG
• Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
• Hepatic transaminases ≤ 2.5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL
• Serum amylase ≤ 5 x ULN
• Adequate hematologic function
• Normal thyroid-stimulating hormone (TSH)
• Females of childbearing potential must have a negative serum pregnancy test
• Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs
• Female subjects who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and hormonal failure
• Female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level test
• Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product

Exclusion Criteria:

• A new AIDS defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface antigen positive
• Hepatitis C antibody positive
• Proven acute hepatitis in the 30 days prior to study entry
• Have a history or experiencing decompensated cirrhosis
• Current alcohol or substance use that potentially interferes with study compliance
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements
• 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
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Female subjects who utilize non-estrogen hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
• Have an implanted defibrillator or pacemaker
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Participation in any other clinical trial without prior approval is prohibited while participating in this trial
• Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with darunavir and cobicistat
• Note: darunavir is a sulfonamide. Participants who previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and darunavir has been identified in patients participating in Phase 2 and Phase 3 trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D/C/F/TAF; D/C/F/TAF FDC tablet plus DRV placebo plus COBI placebo plus FTC/TDF placebo	Drug: FTC/TDF Placebo; FTC/TDF placebo tablet administered orally once daily; Drug: D/C/F/TAF; DRV 800 mg/COBI 150 mg/FTC 200 mg/TAF 10 mg FDC tablet administered orally once daily; Drug: DRV Placebo; DRV placebo tablet administered orally once daily; Drug: COBI Placebo; COBI placebo tablet administered orally once daily
Active Comparator: DRV+COBI+FTC/TDF; DRV tablet plus COBI tablet plus FTC/TDF 200/300 mg FDC tablet plus D/C/F/TAF placebo	Drug: DRV; DRV 800 mg (2 × 400 mg tablets) administered orally once daily; Other Names: Prezista®; Drug: COBI; COBI 150 mg tablet administered orally once daily; Other Names: Tybost®; GS-9350; Drug: FTC/TDF; FTC 200 mg/TDF 300 mg FDC tablet administered orally once daily; Other Names: Truvada®; Drug: D/C/F/TAF Placebo; D/C/F/TAF placebo tablet administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24	The snapshot algorithm was used 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 With HIV-1 RNA < 50 Copies/mL at Week 48	The snapshot algorithm was used 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
Change From Baseline in HIV-1 RNA at Week 24		Baseline; Week 24
Change From Baseline in HIV-1 RNA at Week 48		Baseline; Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Moupali Das, MD, MPH, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: March 27, 2012
• First Submitted That Met QC Criteria: March 27, 2012
• First Posted (Estimate): March 29, 2012

Study Record Updates

• Last Update Posted (Estimate): April 11, 2016
• Last Update Submitted That Met QC Criteria: March 11, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment-Naive
• 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-299-0102