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Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected, Virologically Suppressed Pediatric Participants

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ClinicalTrials.gov Identifier: NCT02016924
Recruitment Status : Active, not recruiting
First Posted : December 20, 2013
Last Update Posted : June 29, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE December 16, 2013
First Posted Date  ICMJE December 20, 2013
Last Update Posted Date June 29, 2020
Actual Study Start Date  ICMJE January 16, 2014
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • Pharmacokinetic (PK) Parameter: AUCtau of ATV and DRV [ Time Frame: Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
  • Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, and TAF for Cohorts 2 and 3 [ Time Frame: Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
  • Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Treatment Emergent Laboratory Abnormalities Through Week 24 [ Time Frame: First dose date and up to 24 weeks plus 30 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 16, 2013)
  • Plasma pharmacokinetics (PK) parameters of ATV and DRV (as measured by AUCtau) [ Time Frame: Baseline to Day 10 ]
    AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
  • Incidence of Treatment-Emergent Adverse Events and Laboratory Abnormalities [ Time Frame: Baseline to Year 5 plus 30 days ]
    Incidence of adverse events and graded laboratory abnormalities will be summarized across the participant population. Graded laboratory abnormalities are those with at least one grade shift from baseline using the Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • PK Parameter: Ctau of ATV, DRV, and COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.
  • PK Parameter: Cmax of ATV, DRV, and COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    Cmax is defined as the maximum observed concentration of drug.
  • PK Parameter: CL/F of ATV, DRV, and COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    CL/F is defined as the apparent oral clearance following administration of the drug.
  • PK Parameter: Vz/F of COBI for Cohort 1 [ Time Frame: Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B). ]
    Vz/F is defined as the apparent volume of distribution of the drug.
  • PK Parameter: Ctau of ATV, DRV, COBI, FTC, and TFV for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.
  • PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    Cmax is defined as the maximum observed concentration of drug.
  • PK Parameter: CL/F of ATV, DRV, and TAF for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    CL/F is defined as the apparent oral clearance following administration of the drug.
  • PK Parameter: Vz/F of COBI and TAF for Cohorts 2 and 3 [ Time Frame: Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48 ]
    Vz/F is defined as the apparent volume of distribution of the drug.
  • The incidence of treatment-emergent AEs and treatment-emergent laboratory abnormalities through Week 48 [ Time Frame: Up to 48 weeks plus 30 days ]
  • The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 and as defined by the US FDA-defined snapshot algorithm [ Time Frame: Week 24 ]
  • The change from baseline in CD4+ cell counts [ Time Frame: Week 24 ]
  • The change from baseline in CD4+ cell counts [ Time Frame: Week 48 ]
  • The change from baseline in CD4+ percentages [ Time Frame: Week 24 ]
  • The change from baseline in CD4+ percentages [ Time Frame: Week 48 ]
  • Acceptability of COBI and F/TAF as Measured by Palatability [ Time Frame: Day 1, and at Weeks 4 (Day 10 for Cohort 1 Part A), 24 and 48. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2013)
  • PK parameters of ATV and DRV (as measured by Ctau, Cmax, CL/F. and Vz/F) and Cobicistat (as measured by AUCtau, Cmax, Ctau, CL/F, and Vz/F) [ Time Frame: Baseline to Year 5 ]
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • Cmax is defined as the maximum concentration of drug
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over 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 copies/mL [ Time Frame: Weeks 12, 24, and 48 ]
  • The time to pure virologic failure [ Time Frame: Baseline to Year 5 ]
    Pure Virologic failure includes participants who do not achieve confirmed suppression (ie, HIV-1 RNA < 50 copies/mL on 2 consecutive visit) or have confirmed rebound (ie, HIV-1 RNA ≥ 50 copies/mL on 2 consecutive visits or the last available HIV-1 RNA ≥ 50 copies/mL during study followed by premature discontinuation of study) after achieving confirmed suppression.
  • Change in CD4+ cell count and CD4 percentage [ Time Frame: Baseline to Weeks 24 and 48 ]
  • Assessment of physical development using Tanner Stages [ Time Frame: Day 1, Weeks 24 and 48, and age of first menses ]
    Tanner Stage assessments will be performed for participants ≥ 6 years of age at the time of the visit, at Day 1, Week 24, and Week 48. Once a participant is determined to be Tanner Stage 5, Tanner Stage assessments will no longer be performed. Date of first menses will be documented.
  • Acceptability (assessed by adherence) and palatability of cobicistat [ Time Frame: Baseline to Year 5 ]
    Acceptability (assessed by adherence) and palatability of COBI tablets and/or dispersible tablets in each cohort will be summarized.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected, Virologically Suppressed Pediatric Participants
Official Title  ICMJE A Phase 2/3, Multicenter, Open-label, Multicohort Study Evaluating Pharmacokinetics (PK), Safety, and Efficacy of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected, Virologically Suppressed Pediatric Participants
Brief Summary

Cohort 1:

The primary objectives are:

  • To evaluate the steady-state pharmacokinetics (PK) of Atazanavir (ATV) and Darunavir (DRV) and confirm the dose of Cobicistat-boosted Atazanavir (ATV/co) or Cobicistat-boosted Darunavir (DRV/co) in HIV-1 infected, virologically suppressed adolescent participants weighing ≥ 25 kg (12 to < 18 years of age)
  • To evaluate the safety and tolerability of ATV/co or DRV/co through 24 weeks in HIV-1 infected, virologically suppressed adolescent participants weighing ≥ 25 kg (12 to < 18 years of age)

Cohort 2:

The primary objectives are:

  • To evaluate the steady-state PK of ATV and DRV and confirm the dose of ATV/co or DRV/co in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age)
  • To evaluate the steady-state PK of tenofovir alafenamide (TAF) and confirm the dose of emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age)
  • To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 25 to < 35 kg (6 to < 12 years of age)

Cohort 3:

The primary objectives are:

  • To evaluate the steady-state PK of ATV and DRV and confirm the dose of ATV/co or DRV/co in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age)
  • To evaluate the steady-state PK of TAF and confirm the dose of F/TAF in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age)
  • To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected, virologically suppressed pediatric participants weighing ≥ 14 to < 25 kg (≥ 3 years of age)
Detailed Description 13April2020: The study recruitment is currently on pause due to the coronavirus disease (COVID-19) pandemic. The overall status will be updated when the study begins recruiting again
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acquired Immune Deficiency Syndrome (AIDS)
  • HIV Infections
Intervention  ICMJE
  • Drug: ATV
    Capsules administered once daily according to dosing recommendations per product monograph
    Other Name: Reyataz®
  • Drug: DRV
    Tablets administered once daily according to dosing recommendations per product monograph
    Other Name: Prezista®
  • Drug: Cobicistat
    Tablets administered orally once daily with food
    Other Names:
    • GS-9350
    • Tybost®
  • Drug: BR
    Prior to implementation protocol amendment 7, Background Regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). After implementation of protocol amendment 7, BR must include 2 NRTIs and a third agent per local prescribing guidelines.
Study Arms  ICMJE
  • Experimental: Part A, Cohort 1
    Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus BR. The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
  • Experimental: Cohort 2
    Participants ages 6 to <12 years old will receive cobicistat 150 mg and emtricitabine/tenofovir alafenamide 200/25 mg with either ATV or DRV.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
  • Experimental: Cohort 3
    Participants ages ≥ 3 will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
  • Experimental: Part B, Cohort 1
    Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus BR. The BR may contain additional antiretroviral agents except for the following disallowed agents: saquinavir, indinavir, nelfinavir, double protease inhibitor (PI) regimens, raltegravir, elvitegravir, efavirenz, nevirapine, delavirdine, maraviroc, etravirine, rilpivirine, dolutegravir, and investigational antiretroviral agents.
    Interventions:
    • Drug: ATV
    • Drug: DRV
    • Drug: Cobicistat
    • Drug: BR
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2020)
80
Original Estimated Enrollment  ICMJE
 (submitted: December 16, 2013)
100
Estimated Study Completion Date  ICMJE April 2026
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • HIV-1 infected treatment-experienced, virologically suppressed males and females aged 3 years to < 18 years at the Day 1 visit (according to requirements of enrolling Cohort)
  • Body weight at screening ≥ 25 kg (Cohorts 1), 14 kg to < 25 kg (Cohort 3)
  • Stable antiretroviral regimen including 2 nucleoside reverse transcriptase inhibitors and either ritonavir-boosted atazanavir or ritonavir-boosted darunavir once or twice daily as per product label for a minimum of 3 months prior to the screening visit. Treatment-experienced pediatric individuals taking DRV/r must have no history of DRV resistance associated mutations.
  • Documented negative screening for active pulmonary tuberculosis (TB) per local standard of care within 6 months of a screening visit

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   South Africa,   Thailand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02016924
Other Study ID Numbers  ICMJE GS-US-216-0128
2013-001402-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date June 2020

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