Clinical Trials

MainTitle

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

This study is ongoing, but not recruiting participants.
Sponsor
Gilead Sciences


Information provided by (Responsible Party)
Gilead Sciences
ClinicalTrials.gov Identifier
NCT02016924

First received: December 16, 2013
Last updated: May 20, 2020
Last Verified: May 2020
History of Changes
Purpose

Purpose

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)

Condition Intervention Phase
Acquired Immune Deficiency Syndrome (AIDS)
HIV Infections

Drug : ATV
Drug : DRV
Drug : Cobicistat
Drug : BR
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Gilead Sciences:

Primary Outcome Measures

  • 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 ]
Secondary Outcome Measures:
  • 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. ]

Estimated Enrollment: 80
Study Start Date: January 16, 2014
Estimated Study Completion Date: April 2026
Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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.
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 Name:
  • 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.

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.
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 Name:
  • GS-9350
  • Tybost®

Experimental: Cohort 3
Participants ages ≥ 3 will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
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 Name:
  • GS-9350
  • Tybost®

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.
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 Name:
  • 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.

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

Eligibility

Eligibility

Ages Eligible for Study: 3 Years to 17 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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.

contacts and locations

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: NCT02016924

Locations

United States, California
Pediatric Infectious Diseases Associate
Long Beach, California, United States, 90806
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
United States, District of Columbia
The George Washington University
Washington, District of Columbia, United States, 20010
United States, Florida
University of South Florida Clinic at Children's Medical Services
Tampa, Florida, United States, 33620
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
University of Texas Health Science Center of Houston
Houston, Texas, United States, 77030
Argentina
Hospital General de Agudos Cosme Argerich
Buenos Aires, Argentina, 1151
Fundacion Huesped
Buenos Aires, Argentina, 1202
Hospital de Pediatría Garrahan
Buenos Aires, Argentina, C1131ACG
South Africa
University of the Free State
Bloemfontein, South Africa, 9300
KIDCRU
Cape Town, South Africa, 7505
Dr. J. Fourie Medical Practice
Dundee, South Africa, 3000
Empilweni Services and Research Unit (ESRU)
Johannesburg, South Africa, 2093
Be Part Yoluntu Centre
Paarl, South Africa, 7626
Vx Pharma
Pretoria, South Africa, 87
Perinatal HIV Research Unit
Soweto, South Africa, 2013
Thailand
Siriraj Hospital
Bangkok, Krung Thep Maha Nakhon, Thailand
The HIV NAT Research Collaboration
Bangkok, Krung Thep Maha Nakhon, Thailand
Srinagarind Hospital
Khon Kaen, Thailand, 40002
United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom, W2 1NY

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director Gilead Sciences
More Information

More Information


Responsible Party: Gilead Sciences  
ClinicalTrials.gov Identifier: NCT02016924   History of Changes  
Other Study ID Numbers: GS-US-216-0128  
  2013-001402-28  
Study First Received: December 16, 2013  
Last Updated: May 20, 2020  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Gilead Sciences:

Pediatrics
Adolescents
HIV
HIV-1
Treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Cobicistat

ClinicalTrials.gov processed this data on June 01, 2020
This information is provided by ClinicalTrials.gov.