Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01854775
First received: May 3, 2013
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

This study is to confirm the dose and evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected, antiretroviral (ARV) treatment naive adolescents. Antiviral activity will be determined by the achievement of HIV-1 RNA < 50 copies/mL at Weeks 24 and 48.


Condition Intervention Phase
Acquired Immune Deficiency Syndrome (AIDS)
HIV Infections
Drug: E/C/F/TAF
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Plasma pharmacokinetics (PK) parameter of EVG as measured by AUCtau and PK parameter of TAF as measured by AUClast [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration

  • Incidence of treatment-emergent serious adverse events and all treatment-emergent adverse events [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Treatment-emergent serious adverse events and adverse events will be summarized.


Secondary Outcome Measures:
  • Percentage of participants with plasma HIV-1 RNA < 50 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Percentage of subjects with plasma HIV-1 RNA < 400 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in plasma log10 HIV-1 RNA (copies/mL) [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count (cells/μL) and percentage [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • PK parameters of EVG as measured by Ctau, Cmax, apparent clearance, and apparent Vz, PK parameters of TAF as measured by Cmax, apparent clearance, and apparent Vz, and PK parameters of FTC, tenofovir (TFV), and COBI as measured by AUCtau, Cmax, and Ctau [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • Cmax is defined as the maximum observed concentration of drug in plasma
    • Vz is defined as the volume of distribution of the drug
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)


Estimated Enrollment: 50
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E/C/F/TAF
Participants will receive E/C/F/TAF STR once daily with food
Drug: E/C/F/TAF
E/C/F/TAF STR tablets contain 150 mg of elvitegravir (EVG), 150 mg of cobicistat (COBI), 200 mg of emtricitabine (FTC), and 10 mg of tenofovir alafenamide (TAF; as 11.2 mg of TAF fumarate)

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. Subjects with screening results that do not meet eligibility criteria will not be allowed to rescreen:

  • 12 years to < 18 years of age at Baseline
  • Weight greater than or equal to 35 kg (77 lbs)
  • Subjects able to give written assent prior to any screening evaluations
  • Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
  • Plasma HIV-1 RNA levels of > 1,000 copies/mL at Screening (Roche COBAS TaqMan v2.0)
  • CD4+ cell count > 100 cells/microliter
  • Screening genotype report shows sensitivity to EVG, FTC and TFV
  • Adequate renal function
  • Clinically normal ECG
  • Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a Screening visit.
  • Hepatic transaminases less than or equal to 5 x upper limit of normal
  • Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin
  • Adequate hematologic function
  • No prior use of any approved or experimental anti-HIV-1 drug for any length of time
  • Negative serum pregnancy test
  • Females of childbearing potential must agree 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 discontinuation of investigational medicinal product.
  • 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 highly effective contraception methods during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from Baseline throughout the study period and for 30 days following discontinuation of investigational medicinal product.
  • Able to swallow oral tablets
  • Must be willing and able to comply with all study requirements
  • Life expectancy > 1 year

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.

  • A new AIDS defining condition diagnosed within the 30 days prior to Screening
  • Positive Hepatitis C antibody
  • Positive Hepatitis B surface antigen or other evidence of active hepatitis B virus infection.
  • Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time
  • Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the Screening visit.
  • Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study.
  • Subjects experiencing decompensated cirrhosis
  • Pregnant or lactating subjects
  • Have an implanted defibrillator or pacemaker
  • Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol.
  • Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance.
  • Have history of significant drug sensitivity or drug allergy.
  • Known hypersensitivity to the study drugs, the metabolites or formulation excipients
  • Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study Screening or expected to receive these agents during the study
  • A history of malignancy within the past 5 years (prior to Screening) 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 Baseline.
  • Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing.
  • Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial.
  • Subjects receiving ongoing therapy with any of the medications in the table below, including drugs not to be used with EVG, COBI, FTC, tenofovir disoproxil fumarate (TDF) and TAF; or subjects with any known allergies to the excipients of E/C/F/TAF STR tablets.
  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: NCT01854775

Contacts
Contact: Skanda Goudar 650-524-4274 skanda.goudar@gilead.com

Locations
United States, California
Miller's Children Hospital Recruiting
Long Beach, California, United States, 90806
Contact    562-933-8590      
Principal Investigator: Jag Batra, MD         
Alta Bates Summit Medical Center Recruiting
Oakland, California, United States, 94609
Contact    510-869-8400      
Principal Investigator: Jeffrey Burack, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact    303-724-3447      
Principal Investigator: Elizabeth McFarland, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20852
Contact    202-476-2083      
Principal Investigator: Natella Rakhmanina, MD         
United States, Florida
University of South Florida - Department of Pediatrics Recruiting
Tampa, Florida, United States, 33606
Contact    813-259-8800      
Principal Investigator: Carina Rodriguez, MD         
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact    404-727-4972      
Principal Investigator: Rana Chakraborty, MD         
United States, New York
New York University Recruiting
New York, New York, United States, 10016
Contact    212-263-6513      
Principal Investigator: William Borkowsky, MD         
SUNY Upstate Medical Center Recruiting
Syracuse, New York, United States, 13210
Contact    315-464-6331      
Principal Investigator: Leonard Weiner, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Coleen Cunningham, MD    919-668-4851      
Principal Investigator: Coleen Cunningham, MD         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact    901-495-5067      
Principal Investigator: Aditya Gaur, MD         
Mexico
Hospital Civil de Gualdalajara Fray Antonio Alcalde Withdrawn
Guadalajara, Jalisco, Mexico, 44280
South Africa
Desmond Tutu HIV Foundation Recruiting
Cape Town, South Africa, 7925
Contact    +021 650 6726      
Principal Investigator: Catherine Orell         
University of Stellenbosch Recruiting
Cape Town, South Africa, 7522
Contact    +2721 938 4302      
Principal Investigator: Mark Cotton         
Be Part Yoluntu Centre Recruiting
Cape Town, South Africa, 7646
Contact    +021868399012      
Principal Investigator: Elizabeth Hellstrom         
Mpati Medical Centre Recruiting
Dundee, South Africa, 3000
Contact    +011 27-342182092      
Principal Investigator: Jan Fourie         
Gulam Latiff Private Practice Recruiting
Durban, South Africa, 4001
Contact    +011 27 31 309 3245      
Principal Investigator: Gulam Latiff         
Clinical HIV Research Unit Recruiting
Johannesburg, South Africa, 2092
Contact    +011-2711 276 8800      
Principal Investigator: Mohammed Rassool         
Rahima Moosa Mother and Child Hopsital Recruiting
Johannesburg, South Africa, 2112
Contact    +011 27 11 470 9168      
Principal Investigator: Renate Strehlau         
Perinatal HIV Research Unit Recruiting
Soweto, South Africa, 2013
Contact    +011-27-11-989-9700      
Principal Investigator: Avy Violari         
Thailand
The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT) Recruiting
Pathumwan, Bangkok, Thailand, 10330
Contact    02 652 3040 ext 134      
Principal Investigator: Wasana Pasitsuebsai, MD         
Department of Pediatrics, Faculty of Medicine, Khon Kaen University Recruiting
Muang, Khon Kaen, Thailand, 40002
Contact    043 34 88 32      
Principal Investigator: Pope Kosalaraksa, MD         
Queen Savang Vadhana Memorial Hospital Recruiting
Chonburi, Thailand, 20110
Contact    +66 383 255 90      
Principal Investigator: Wicharn Luesomboon         
Uganda
Joint Clinical Research Centre Recruiting
Lubowa Hill, Kampala, Uganda, PO Box 10005
Contact    +256414201148      
Principal Investigator: Hilda Kizito, MD         
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Sean Bennett, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01854775     History of Changes
Other Study ID Numbers: GS-US-292-0106, 2013-002780-26
Study First Received: May 3, 2013
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Adolescents
HIV-1
HIV
Treatment-naive

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

ClinicalTrials.gov processed this record on July 10, 2014