Two Part Study to Study Pharmacokinetics, Safety, and Antiviral Activity of Elvitegravir (EVG) Administered With a PI/r Background Regimen for ARV Treatment-Experienced Pediatric Subjects

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:
NCT01923311
First received: August 9, 2013
Last updated: August 19, 2014
Last verified: August 2014

August 9, 2013
August 19, 2014
August 2013
July 2016   (final data collection date for primary outcome measure)
  • Plasma pharmacokinetics (PK) parameters of EVG as measured by AUCtau and Cmax [ Time Frame: Day 10 ] [ 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)
    • Cmax is defined as the maximum concentration of drug
  • Incidence of treatment-emergent adverse events and laboratory abnormalities [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    The incidence of treatment-emergent adverse events and laboratory abnormalities will be summarized.
  • Measure plasma concentrations of EVG over sampling time to evaluate the steady state PK for EVG and confirm the dose of EVG. [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    Calculation of plasma PK parameters for AUCtau and Cmax of EVG
  • Incidence of treatment-emergent adverse events and laboratory abnormalities [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
    To evaluate the incidence of treatment-emergent AEs and lab abnormalities inclusive of all subjects who received at least one dose of study drug.
Complete list of historical versions of study NCT01923311 on ClinicalTrials.gov Archive Site
  • PK parameters of EVG as measured by Ctau, CL/F, and Vz/F [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • CL/F is the apparent oral clearance following administration of the drug
    • Vz/F is the apparent volume of distribution of the drug
  • Percentage of participants with plasma HIV-1 RNA < 50 and < 400 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in plasma log10 HIV-1 RNA [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Tanner Stages at Weeks 24 and 48, and age of first menses [ Time Frame: Weeks 24 and 48 and age of first menses ] [ Designated as safety issue: No ]
    Tanner Stages at Weeks 24 and 48 will be summarized by baseline Tanner Stage using frequency and percentage. Age of first menses will be summarized descriptively.
  • Palatability of oral suspension formulation of EVG in appropriate age group [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Adherence to EVG [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    Treatment adherence will be assessed at all post-baseline visits.
  • The change from baseline in CD4+ cell count (cells/μL) [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • The change from baseline in CD4 percentage [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Subjects with HIV-1 RNA less than 50 and less than 400 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
    Percentage of subjects with HIV-1 RNA less than 50 and 400 copies/mL at Weeks 24 and 48 as defined by the FDA snapshot analysis, respectively.
  • Plasma log10 HIV-1 RNA [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in plasma log10 HIV-1 RNA at Weeks 24 and 48.
  • CD4+ cell counts and CD4 percentage [ Time Frame: Week 24 and Week 48 ] [ Designated as safety issue: No ]
    Change from baseline in CD4+ cell counts and CD4 percentage at Weeks 24 and 48.
Not Provided
Not Provided
 
Two Part Study to Study Pharmacokinetics, Safety, and Antiviral Activity of Elvitegravir (EVG) Administered With a PI/r Background Regimen for ARV Treatment-Experienced Pediatric Subjects
A Phase 2/3 Multicenter, Open-Label, Multicohort, Two-Part Study Evaluating the Pharmacokinetics (PK), Safety, and Antiviral Activity of Elvitegravir (EVG)Administered With a Background-Regimen (BR) Containing a Ritonavir-Boosted Protease Inhibitor (PI/r) in HIV-1 Infected, Antiretroviral Treatment-Experienced Pediatric Subjects

This is an open-label, multicenter, multicohort, two-part study to confirm the dose and evaluate the safety and tolerability of ritonavir-boosted elvitegravir (EVG/r) in HIV-1 infected, treatment-experienced subjects aged 4 weeks to less than 18 years of age. The dose of EVG will be determined by intensive pharmacokinetic sampling at Day 10. The safety and antiviral activity of EVG will also be evaluated.

Not Provided
Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acquired Immune Deficiency Syndrome (AIDS)
  • HIV Infections
  • Drug: Elvitegravir
    EVG (50 mg, 85 mg, or 150 mg tablets or 5 mg/mL powder for oral suspension) administered orally once daily with food
  • Drug: RTV-boosted PI

    Participants will receive a background regimen consisting of ritonavir (RTV; /r)-boosted protease inhibitor (PI/r). The PI/r contained in the background regimen must be one of the following: lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For subjects < 2 months old, only lopinavir/r is allow. Use of additional antiretrovirals in background therapy may be allowed.

    • Participants with HIV-1 RNA < 50 copies/mL will receive their current PI/r as background regimen
    • Participants with HIV-1 RNA > 1,000 copies/mL will receive a newly constructed PI/r background regimen selected by the investigator.
  • Experimental: Cohort 1

    Participants age 12 to 17 will be enrolled.

    • Part A: No participants will be enrolled in Part A, as PK data is currently available for this age group.
    • Part B: Participants will receive Elvitegravir (EVG) plus a background regimen that includes a PI/r for up to 48 weeks.
    Interventions:
    • Drug: Elvitegravir
    • Drug: RTV-boosted PI
  • Experimental: Cohort 2

    Participants age 6 to 11 will be enrolled in Part A first. After pharmacokinetic (PK) assessment of Part A, participants will be enrolled in Part B.

    • Part A: Participants will receive Elvitegravir (EVG) plus a background regimen that includes a PI/r for 10 days. Participants with HIV-1 RNA > 1,000 copies/mL who complete Part A may then choose to continue in Part B.
    • Part B: Following PK assessment, participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks.
    Interventions:
    • Drug: Elvitegravir
    • Drug: RTV-boosted PI
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
86
October 2016
July 2016   (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.

  • HIV-1 infected male and female subjects 4 weeks (gestational age of at least 44 weeks) to less than 18 years of age at Baseline.
  • Subjects are able to provide written assent if they have the ability to read and write.
  • Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements.
  • Body weight at screening greater than 5kg, 10.6kg, or 15kg dependent upon age cohort
  • Adequate renal function
  • Adequate hematologic function
  • Hepatic transaminases (AST and ALT) less than or equal to 5 x upper limit of normal (ULN)
  • Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin
  • Negative serum pregnancy test
  • Subjects with evidence of suppressed viremia
  • Subjects failing a current antiretroviral regimen at study entry
  • Male and female subjects of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days following the last dose of study drug
  • Must be willing and able to comply with all study requirements.

Exclusion Criteria:

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

  • Subjects with CD4+ cell counts at Screening of less than 50, 75, or 200 cells/mm3 dependent on age cohort
  • An AIDS defining condition with onset within 30 days prior to screening
  • Life expectancy of less than 1 year
  • For subjects with HIV-1 RNA greater than 1,000 copies/mL at screening, prior treatment of any duration with an integrase strand transfer inhibitor.
  • An ongoing serious infection requiring systemic antibiotic therapy at the time of screening.
  • Evidence of active pulmonary or extra-pulmonary tuberculosis disease
  • Anticipated requirement for rifamycin treatment while participating in the study.
  • 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.
  • Subjects experiencing decompensated cirrhosis
  • A history of or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
  • Pregnant or lactating subjects.
  • 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 drug, the metabolites, or formulation excipients.
  • 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 medication that is not to be taken with EVG or a component of the BR, including drugs not to be used with ritonavir
Both
up to 17 Years
No
Contact: Gilead Study Team GSUS1830160@gilead.com
United States,   Germany,   Italy,   South Africa,   Spain,   Thailand,   Uganda
 
NCT01923311
GS-US-183-0160, 2013-001969-16
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Sean Bennett, MD, PhD Gilead Sciences
Gilead Sciences
August 2014

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