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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 currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01854775
First received: May 3, 2013
Last updated: December 5, 2016
Last verified: December 2016
  Purpose

There will be 2 cohorts in this study, each consisting of Part A and Part B.

The primary objectives of Cohort 1 are to evaluate the steady state pharmacokinetics (PK) for elvitegravir (EVG) and tenofovir alafenamide (TAF) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 (Part B) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.

The primary objectives of Cohort 2 are to evaluate the PK of EVG and TAF in virologically suppressed HIV-1 infected children 6 to < 12 years of age weighing ≥ 25 kg administered E/C/F/TAF STR (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 in virologically suppressed HIV-1 infected children 6 to < 12 years of age weighing ≥ 25 kg.


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 (Part A) [ Time Frame: Predose and up to 24 hours postdose ] [ Designated as safety issue: No ]
    AUCtau is defined as concentration of drug over a dosing interval.

  • PK Parameter: AUClast for TAF (Part A) [ Time Frame: Predose and up to 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 (Part B) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • Incidence of All Treatment-Emergent Adverse Events (Part B) [ 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 as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Percentage of Participants with Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants with Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Change from Baseline in Plasma log10 HIV-1 RNA (copies/mL) at Week 24 (Cohort 1 Part B only) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
  • Change from Baseline in Plasma log10 HIV-1 RNA (copies/mL) at Week 48 (Cohort 1 Part B only) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
  • Change from Baseline in CD4+ Cell Count (cells/μL) at Week 24 (Part B) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
  • Change from Baseline in CD4+ Cell Count (cells/μL) at Week 48 (Part B) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
  • Percentage Change from Baseline in CD4+ Cell Count (cells/μL) at Week 24 (Part B) [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
  • Percentage Change from Baseline in CD4+ Cell Count (cells/μL) at Week 48 (Part B) [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
  • PK Parameter: Ctau for EVG, FTC, TFV, and COBI (Part A) [ Time Frame: Predose and up to 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: Cmax for EVG, TAF, FTC, TFV, and COBI (Part A) [ Time Frame: Predose and up to 24 hours postdose ] [ Designated as safety issue: No ]
    Cmax is defined as the maximum concentration of drug.

  • PK Parameter: Apparent CL for EVG and TAF (Part A) [ Time Frame: Predose and up to 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 Vz for EVG and TAF (Part A) [ Time Frame: Predose and up to 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: AUCtau for FTC, TFV, and COBI (Part A) [ Time Frame: Predose and up to 24 hours postdose ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: May 2013
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: October 2017 (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   (Child)
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 tenofovir (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.

Key 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

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

  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: Gilead Study Team GS-US-292-0106@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 Active, not recruiting
Oakland, California, United States, 94609
United States, Colorado
Children's Hospital Colorado Active, not recruiting
Aurora, Colorado, United States, 80045
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 Active, not recruiting
Tampa, Florida, United States, 33606
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 Active, not recruiting
New York, New York, United States, 10016
SUNY Upstate Medical Center Active, not recruiting
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University Medical Center Active, not recruiting
Durham, North Carolina, United States, 27710
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
University of Stellenbosch Active, not recruiting
Cape Town, South Africa, 7522
Be Part Yoluntu Centre Withdrawn
Cape Town, South Africa, 7646
Desmond Tutu HIV Foundation Active, not recruiting
Cape Town, South Africa, 7925
Mpati Medical Centre Active, not recruiting
Dundee, South Africa, 3000
Gulam Latiff Private Practice Active, not recruiting
Durban, South Africa, 4001
Clinical HIV Research Unit Active, not recruiting
Johannesburg, South Africa, 2092
Rahima Moosa Mother and Child Hopsital Active, not recruiting
Johannesburg, South Africa, 2112
Perinatal HIV Research Unit Active, not recruiting
Soweto, South Africa, 2013
Thailand
The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT) Active, not recruiting
Pathumwan, Bangkok, Thailand, 10330
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 Active, not recruiting
Chonburi, Thailand, 20110
Uganda
Joint Clinical Research Centre Recruiting
Lubowa Hill, Kampala, Uganda, PO Box 10005
Contact    +256414201148      
Principal Investigator: Eva Natukunda, MD         
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director 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: December 5, 2016
Health Authority: United States: Food and Drug Administration
Thailand: Food and Drug Administration
Uganda: National Drug Authority
South Africa: Medicines Control Council

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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immune System Diseases
Slow Virus Diseases
Tenofovir
Antiviral Agents
Emtricitabine
Cobicistat
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on December 07, 2016