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 August 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01854775
First received: May 3, 2013
Last updated: August 18, 2014
Last verified: August 2014

May 3, 2013
August 18, 2014
May 2013
December 2014   (final data collection date for primary outcome measure)
  • 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.
  • Incidence of treatment-emergent SAEs [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    To evaluate the incidence of treatment-emergent SAEs and all treatment-emergent adverse events inclusive of all subjects who received at least one dose of study drug.
  • Measure plasma concentrations of EVG, TAF, COBI, FTC and TFV over sampling time to evaluate the steady state PK for EVG and TAF and confirm the dose of the E/C/F/TAF STR. [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Calculation of plasma PK parameters for AUCtau for EVG and AUClast for TAF.
Complete list of historical versions of study NCT01854775 on ClinicalTrials.gov Archive Site
  • 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)
  • The percentage of subjects with plasma HIV 1 RNA less than 50 copies/mL [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
    The percentage of subjects with plasma HIV 1 RNA less than 50 copies/mL at Week 24 and 48 as defined by the FDA snapshot analysis.
  • The percentage of subjects with plasma HIV 1 RNA less than 400 copies/mL [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
    The percentage of subjects with plasma HIV 1 RNA less than 400 copies/mL at Week 24 and 48 as defined by the FDA snapshot analysis.
  • The change from baseline in plasma log10 HIV 1 RNA (copies/mL) and in CD4+ cell count (cells/μL) and percentage [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
    The change from baseline in plasma log10 HIV 1 RNA (copies/mL) and in CD4+ cell count (cells/μL) and percentage at Week 24 and 48.
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 2
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acquired Immune Deficiency Syndrome (AIDS)
  • HIV Infections
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)
Experimental: E/C/F/TAF
Participants will receive E/C/F/TAF STR once daily with food
Intervention: Drug: E/C/F/TAF
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
May 2015
December 2014   (final data collection date for primary outcome measure)

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.
Both
12 Years to 17 Years
No
Contact: Skanda Goudar 650-524-4274 skanda.goudar@gilead.com
United States,   Mexico,   South Africa,   Thailand,   Uganda
 
NCT01854775
GS-US-292-0106, 2013-002780-26
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Sean Bennett, MD Gilead Sciences
Gilead Sciences
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP