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 and Virologically Suppressed Children

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01854775
First received: May 3, 2013
Last updated: April 29, 2016
Last verified: April 2016
  Purpose
This study is to confirm the dose of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single tablet regimen (STR) in HIV-1 infected, antiretroviral (ARV) treatment naive adolescents and evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of E/C/F/TAF STR in HIV-1 infected, ARV treatment naive adolescents and virologically suppressed HIV-1 infected children. 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: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel 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 and Virologically Suppressed Children

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Pharmacokinetic (PK) Parameter: AUCtau for EVG [ Time Frame: predose, 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours postdose ] [ Designated as safety issue: No ]
    AUCtau is defined as concentration of drug over a dosing interval.

  • PK Parameter: AUClast for EVG and TAF [ Time Frame: predose, 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours postdose ] [ Designated as safety issue: No ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  • Incidence of treatment-emergent serious adverse events [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of all treatment-emergent adverse events [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]

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 participants 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: Baseline; Week 24; Week 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 Parameter: Ctau of EVG and COBI [ Time Frame: predose, 1, 2, 3, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  • PK Parameter: Ctau of FTC [ Time Frame: predose, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: Ctau of TFV [ Time Frame: predose, 1, 2, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: Cmax of EVG and COBI [ Time Frame: predose, 1, 2, 3, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    Cmax is defined as the maximum concentration of drug.

  • PK Parameter: Cmax of FTC [ Time Frame: predose, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: Cmax of TAF [ Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: Cmax of TFV [ Time Frame: predose, 1, 2, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: Apparent CL of EVG [ Time Frame: predose, 1, 2, 3, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    Apparent clearance (CL) is defined as the systemic clearance of the drug following oral administration.

  • PK Parameter: Apparent CL of TAF [ Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: Apparent Vz of EVG [ Time Frame: predose, 1, 2, 3, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
    Apparent Vz is defined as the apparent volume of distribution of the drug after oral administration.

  • PK Parameter: Apparent Vz of TAF [ Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: AUCtau for FTC [ Time Frame: predose, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: AUCtau for TFV [ Time Frame: predose, 1, 2, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]
  • PK Parameter: AUCtau for COBI [ Time Frame: predose, 1, 2, 3, 4, 5, 8, and 24 hours postdose ] [ Designated as safety issue: No ]

Enrollment: 73
Study Start Date: May 2013
Estimated Study Completion Date: December 2021
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (12 to < 18 years of age)
Participants within the ages of 12 and <18 years old will receive E/C/F/TAF STR once daily with food.
Drug: E/C/F/TAF
E/C/F/TAF 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)
Experimental: Cohort 2 (6 to < 12 years of age)
Participants within the ages of 6 and <12 years old and weighing ≥ 25 kg will receive E/C/F/TAF STR once daily with food.
Drug: E/C/F/TAF
E/C/F/TAF 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:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Cohort 1

    • 12 years to < 18 years of age at baseline
    • Weight greater than or equal to 35 kg (77 lbs)
    • Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL at screening (Roche COBAS TaqMan v2.0)
    • Screening genotype report shows sensitivity to EVG, FTC and TFV
    • No prior use of any approved or experimental anti-HIV-1 drug for any length of time
  • Cohort 2

    • 6 years to < 12 years of age at baseline
    • Weight greater than or equal to 25 kg (55 lbs)
    • Plasma HIV-1 RNA of < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is > 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to screening on a stable antiretroviral regimen, without documented history of resistance to any component of E/C/F/TAF STR.

Exclusion Criteria:

  • Hepatitis B or hepatitis C virus infection
  • Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit.
  • Individuals experiencing decompensated cirrhosis
  • Pregnant or lactating females
  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

Locations
United States, California
Miller's Children Hospital
Long Beach, California, United States, 90806
Alta Bates Summit Medical Center
Oakland, California, United States, 94609
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20852
United States, Florida
University of South Florida - Department of Pediatrics
Tampa, Florida, United States, 33606
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, New York
New York University
New York, New York, United States, 10016
SUNY Upstate Medical Center
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
South Africa
University of Stellenbosch
Cape Town, South Africa, 7522
Desmond Tutu HIV Foundation
Cape Town, South Africa, 7925
Mpati Medical Centre
Dundee, South Africa, 3000
Gulam Latiff Private Practice
Durban, South Africa, 4001
Clinical HIV Research Unit
Johannesburg, South Africa, 2092
Rahima Moosa Mother and Child Hopsital
Johannesburg, South Africa, 2112
Perinatal HIV Research Unit
Soweto, South Africa, 2013
Thailand
The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)
Pathumwan, Bangkok, Thailand, 10330
Department of Pediatrics, Faculty of Medicine, Khon Kaen University
Muang, Khon Kaen, Thailand, 40002
Queen Savang Vadhana Memorial Hospital
Chonburi, Thailand, 20110
Uganda
Joint Clinical Research Centre
Lubowa Hill, Kampala, Uganda, PO Box 10005
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Devi SenGupta, MD Gilead Sciences
  More Information

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: April 29, 2016
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
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
Emtricitabine
Tenofovir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on May 02, 2016