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Study of Cobicistat-Boosted Atazanavir (ATV/co), Cobicistat-Boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in Children With HIV

Primary Purpose

Acquired Immune Deficiency Syndrome (AIDS), HIV Infections

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ATV
DRV
Cobicistat
BR
F/TAF
LPV/r
Third Unboosted Drug
Cobicistat TOS
F/TAF TOS
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acquired Immune Deficiency Syndrome (AIDS) focused on measuring Pediatrics, Adolescents, HIV, HIV-1, Treatment experienced

Eligibility Criteria

4 Weeks - 17 Years (Child)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • HIV-1 infected, virologically suppressed males and females Age ≥ 4 weeks to < 18 years (according to requirements of enrolling Cohort).
  • Body weight at screening ≥ 25 to < 40 kg (Cohort 2); ≥ 14 to < 25 kg (Cohort 3); ≥ 3 to < 25 kg (Cohort 4); ≥ 3 to < 14 kg (Cohort 5)
  • Stable antiretroviral (ARV) regimen for a minimum of 3 months prior to the screening visit.

    • Participants enrolled prior to implementation of Amendment 7: 2 NRTIs and ATV/r once daily or DRV/r once daily or twice daily.
    • Participants enrolled after the implementation of Amendment 9:

      • Cohorts 2, 3 and 4 (Group 1): 2 NRTIs plus a third agent per local prescribing guidelines. Participants will switch from their current third agent to ATV or DRV at Day 1. Participants taking DRV must be on once-daily dosing or must switch to once daily at or prior to Day 1. Cohort 4 (Group 1), participants may also switch their current third agent to LPV/r at Day 1. Participants will switch their NRTI backbone to F/TAF.
      • Cohort 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3): 2 NRTIs plus a third agent per local prescribing guidelines or treatment naive. Participants on treatment will switch from their current third agent to ATV or LPV/r (Cohort 4 [Groups 2 to 4]), or to a third unboosted agent (Cohort 5 [Groups 1 to 3]). Participants will switch their NRTI backbone to F/TAF.
  • Participants undergoing dose modifications to their ARV regimen for growth or switching medication formulations are considered to be on a stable ARV regimen.
  • Documented plasma HIV-1 RNA for ≥ 3 months preceding the screening visit:

    • Participants enrolled after the implementation of Amendment 9:

      • For Cohorts 2, 3, and 4 (Group 1), virologically suppressed ≥ 3 months preceding the screening visit: HIV-1 RNA < 50 copies/mL on a stable regimen (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL)
      • For Cohorts 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3), on an ARV regimen irrespective of plasma HIV-1 RNA copies or treatment naive; a participant is considered treatment naive if ARVs were given for prevention of mother-to-child transmission but not for HIV treatment
    • For virologically suppressed participants, unconfirmed virologic elevations of HIV-1 RNA ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL (eg, < 20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on 2 consecutive HIV-1 RNA tests.
  • Adequate renal function: Estimated Glomerular Filtration Rate (eGFR) ≥ 90 mL/min/1.73m2 using the Schwartz formula. If ≥ 1 year old, eGFR greater than or equal to the minimum normal value for age using the Schwartz Formula. If < 1 year old as follows:

    • Age Minimum Value for eGFR (mL/min/1.73 m2) > 28 days to ≤ 95 days 30, ≥ 96 days to ≤ 6 months 39, > 6 to < 12 months 49
  • Participants must not have documented or suspected resistance to applicable study drugs including FTC, TFV, ATV, DRV, or LPV. Participants < 14 kg (Cohorts 4 [Groups 2 to 4] and 5 [Groups 1 to 3]) with M184V/I AND HIV-1 RNA < 50 copies/mL will be allowed.
  • Positive confirmatory HIV test (confirmatory nucleic acid-based testing if < 18 months of age).
  • Cohort 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3): Last dose of nevirapine or efavirenz, if applicable, ≥ 14 days prior to enrollment.

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

Sites / Locations

  • Pediatric Infectious Disease Associates
  • Jeffrey Goodman Special Care Clinic
  • Peter Morton Medical Building
  • University of Colorado Denver
  • The George Washington University
  • University of South Florida
  • Emory-Children's Center- Ponce Family and Youth Clinic
  • Boston University Medical Center
  • New York University School of Medicine
  • SUNY Upstate Medical University
  • St. Jude Children's Research Hospital
  • University of Texas Health Science Center of Houston
  • Hospital General de Agudos Cosme Argerich
  • Fundacion Huesped
  • Helios Salud
  • Hospital Jose Maria Ramos Mejia
  • Hopital del Nino
  • University of the Free State
  • University of StellenboschRecruiting
  • Dr. J. Fourie Medical Practice
  • King Edward VIII HospitalRecruiting
  • Rahima Moosa Mother and Child HospitalRecruiting
  • Be Part Yoluntu Centre
  • The Aurum Institute: Pretoria Clinical Research CentreRecruiting
  • Perinatal HIV Research UnitRecruiting
  • HIV-NATRecruiting
  • Siriraj HospitalRecruiting
  • Srinagarind Hospital
  • Queen Savang Vadhana Memorial Hospital
  • MU-JHU Research Collaboration/MU-JHU Care Ltd
  • Imperial College Healthcare NHS Trust
  • University of Zimbabwe Clinical Research CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: Part A and Part B

Cohort 2 (Group 1)

Cohort 2 (Group 2)

Cohort 3

Cohort 4 (Group 1)

Cohort 4 (Group 2)

Cohort 4 (Group 3)

Cohort 4 (Group 4)

Cohort 5 (Group 1)

Cohort 5 (Group 2)

Cohort 5 (Group 3)

Arm Description

Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus background regimen (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.

After Protocol Amendment 9, Cohort 2 weight range will be modified to ≥ 25 to < 40 kg. Group 1 will be the current weight/age range for Cohort 2, participants aged 6 to <12 years old and ≥ 25 to < 35 kg. They will receive cobicistat (co) 150 mg and emtricitabine/tenofovir alafenamide (F/TAF) 20/25 mg with either ATV or DRV.

After Protocol Amendment 9, Cohort 2 weight range will be modified to ≥ 25 to < 40 kg. Group 2 will be the new weight range for Cohort 2, participants aged 6 to <12 years old and ≥ 35 to < 40 kg. They will receive cobicistat (co) 150 mg and emtricitabine/tenofovir alafenamide (F/TAF) 20/25 mg with DRV

Participants ages ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.

Participants age ≥ 4 weeks old weighing 14 to < 25 kg will receive cobicistat tablet for oral suspension (TOS) 90 mg, once daily and F/TAF TOS 120/15 mg, once daily with either ATV or DRV or lopinavir boosted by ritonavir (LPV/r). Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, minimum age and weight for DRV is ≥ 3 years and ≥ 15 kg; participants receiving LPV/r will not receive cobicistat TOS.

Participants age ≥ 4 weeks old weighing 10 to < 14 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 60/7.5 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.

Participants age ≥ 4 weeks old weighing 6 to < 10 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 30/3.75 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.

Participants age ≥ 4 weeks old weighing 3 to < 6 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 15/1.88 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.

Participants ages ≥ 4 weeks old weighing ≥ 10 to < 14 kg will receive F/TAF TOS 60/7.5 mg, once daily with the third unboosted drug.

Participants ages ≥ 4 weeks old weighing ≥ 6 to < 10 kg will receive F/TAF TOS 30/3.75 mg, once daily with the third unboosted drug.

Participants ages ≥ 4 weeks old weighing ≥ 3 to < 6 kg will receive F/TAF TOS 15/1.88 mg, once daily with the third unboosted drug.

Outcomes

Primary Outcome Measures

Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, TAF, and TFV
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). AUCtau for ATV (Cohorts 1 Part A, 2, 3, and 4 [Groups 2 to 4]); DRV (Cohorts 1 Part A, 2, and 3); TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 [Groups 1 to 3] taking F/TAF); and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 [Groups 1 to 3] taking F/TAF) will be reported.
Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) Through Week 24
Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities Through Week 24

Secondary Outcome Measures

PK Parameter: Ctau of ATV, DRV, TAF, and TFV
Ctau is defined as the observed drug concentration at the end of the dosing interval. Ctau for ATV (cohorts 1, 2, 3, and 4 (Groups 2 to 4)), DRV (cohorts 1, 2, and 3), COBI (except Cohort 5), FTC and TFV (cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV
Cmax is defined as the maximum observed concentration of drug. Cmax for ATV (Cohorts 1, 2, 3, and 4 [Groups 2 to 4]) and DRV (Cohorts 1, 2, and 3); for COBI (except Cohort 5); for TAF, FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
PK Parameter: CL/F of ATV, DRV, COBI, TAF, FTC and TFV
CL/F is defined as the apparent oral clearance following administration of the drug. CL/F for ATV (Cohorts 1, 2, 3, and 4 [Groups 2 to 4]) and DRV (Cohorts 1, 2, and 3); for COBI (except Cohort 5); for TAF, FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
PK Parameter: Vz/F of COBI, TAF, FTC and TFV
Vz/F is defined as the apparent volume of distribution of the drug. Vz/F for COBI (Except Cohort 5); for TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF); for FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
PK Parameter: AUCtau of COBI, FTC and TFV
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). AUCtau for COBI (Except Cohort 5); for FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
PK Parameter: AUClast of TAF, FTC and TFV
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. AUClast for TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF); for FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
PK Parameter: Clast of TAF
Clast is defined as the the last observed quantifiable concentration of the drug in plasma. Clast for TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
Percentage of Participants with HIV-1 RNA < 50 Copies/mL at Week 24 and as Defined by the US FDA-defined Snapshot Algorithm
Percentage of Participants with HIV-1 RNA < 50 Copies/mL at Week 48 and as Defined by the US FDA-defined Snapshot Algorithm
Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 24
Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 48
Change from Baseline in Percentage of CD4+ Cells at Week 24
Change from Baseline in Percentage of CD4+ Cells at Week 48
Acceptability of COBI and F/TAF as Measured by Palatability Score

Full Information

First Posted
December 16, 2013
Last Updated
September 22, 2023
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02016924
Brief Title
Study of Cobicistat-Boosted Atazanavir (ATV/co), Cobicistat-Boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in Children With HIV
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 16, 2014 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
March 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this clinical study is to learn more about the safety and dosing of study drugs, cobicistat-boosted Atazanavir (ATV/co), cobicistat-boosted darunavir (DRV/co) and emtricitabine/tenofovir alafenamide (F/TAF), in children (age ≥ 4 weeks to < 18 years) with HIV.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acquired Immune Deficiency Syndrome (AIDS), HIV Infections
Keywords
Pediatrics, Adolescents, HIV, HIV-1, Treatment experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Part A and Part B
Arm Type
Experimental
Arm Description
Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus background regimen (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.
Arm Title
Cohort 2 (Group 1)
Arm Type
Experimental
Arm Description
After Protocol Amendment 9, Cohort 2 weight range will be modified to ≥ 25 to < 40 kg. Group 1 will be the current weight/age range for Cohort 2, participants aged 6 to <12 years old and ≥ 25 to < 35 kg. They will receive cobicistat (co) 150 mg and emtricitabine/tenofovir alafenamide (F/TAF) 20/25 mg with either ATV or DRV.
Arm Title
Cohort 2 (Group 2)
Arm Type
Experimental
Arm Description
After Protocol Amendment 9, Cohort 2 weight range will be modified to ≥ 25 to < 40 kg. Group 2 will be the new weight range for Cohort 2, participants aged 6 to <12 years old and ≥ 35 to < 40 kg. They will receive cobicistat (co) 150 mg and emtricitabine/tenofovir alafenamide (F/TAF) 20/25 mg with DRV
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Participants ages ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
Arm Title
Cohort 4 (Group 1)
Arm Type
Experimental
Arm Description
Participants age ≥ 4 weeks old weighing 14 to < 25 kg will receive cobicistat tablet for oral suspension (TOS) 90 mg, once daily and F/TAF TOS 120/15 mg, once daily with either ATV or DRV or lopinavir boosted by ritonavir (LPV/r). Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, minimum age and weight for DRV is ≥ 3 years and ≥ 15 kg; participants receiving LPV/r will not receive cobicistat TOS.
Arm Title
Cohort 4 (Group 2)
Arm Type
Experimental
Arm Description
Participants age ≥ 4 weeks old weighing 10 to < 14 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 60/7.5 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.
Arm Title
Cohort 4 (Group 3)
Arm Type
Experimental
Arm Description
Participants age ≥ 4 weeks old weighing 6 to < 10 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 30/3.75 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.
Arm Title
Cohort 4 (Group 4)
Arm Type
Experimental
Arm Description
Participants age ≥ 4 weeks old weighing 3 to < 6 kg will receive cobicistat TOS 30 mg (twice daily) and F/TAF TOS 15/1.88 mg, once daily with either ATV or LPV/r. Minimum age and weight for ATV is ≥ 3 months and ≥ 5 kg, respectively; participants receiving LPV/r will not receive cobicistat TOS.
Arm Title
Cohort 5 (Group 1)
Arm Type
Experimental
Arm Description
Participants ages ≥ 4 weeks old weighing ≥ 10 to < 14 kg will receive F/TAF TOS 60/7.5 mg, once daily with the third unboosted drug.
Arm Title
Cohort 5 (Group 2)
Arm Type
Experimental
Arm Description
Participants ages ≥ 4 weeks old weighing ≥ 6 to < 10 kg will receive F/TAF TOS 30/3.75 mg, once daily with the third unboosted drug.
Arm Title
Cohort 5 (Group 3)
Arm Type
Experimental
Arm Description
Participants ages ≥ 4 weeks old weighing ≥ 3 to < 6 kg will receive F/TAF TOS 15/1.88 mg, once daily with the third unboosted drug.
Intervention Type
Drug
Intervention Name(s)
ATV
Other Intervention Name(s)
Reyataz®
Intervention Description
Capsules administered once daily according to dosing recommendations per product monograph
Intervention Type
Drug
Intervention Name(s)
DRV
Other Intervention Name(s)
Prezista®
Intervention Description
Tablets administered once daily according to dosing recommendations per product monograph
Intervention Type
Drug
Intervention Name(s)
Cobicistat
Other Intervention Name(s)
GS-9350, Tybost®
Intervention Description
Tablets administered orally once daily with food
Intervention Type
Drug
Intervention Name(s)
BR
Intervention Description
Background Regimen (BR) include Food and Drug Administration (FDA)-approved nucleos(t)ide reverse transcriptase inhibitors (NRTIs) including zidovudine (ZDV), stavudine (d4T), didanosine (ddI), abacavir (ABC), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), lamivudine (3TC), and emtricitabine (FTC).
Intervention Type
Drug
Intervention Name(s)
F/TAF
Other Intervention Name(s)
Descovy®
Intervention Description
Tablets administered orally once daily
Intervention Type
Drug
Intervention Name(s)
LPV/r
Intervention Description
Solution administered orally
Intervention Type
Drug
Intervention Name(s)
Third Unboosted Drug
Intervention Description
ATV (administered orally), DRV (administered orally), and LPV/r (administered orally) would be general list but unspecified for sites.
Intervention Type
Drug
Intervention Name(s)
Cobicistat TOS
Other Intervention Name(s)
GS-9350, Tybost®
Intervention Description
Tablets for oral suspension
Intervention Type
Drug
Intervention Name(s)
F/TAF TOS
Other Intervention Name(s)
Descovy®
Intervention Description
Tablets for oral suspension
Primary Outcome Measure Information:
Title
Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, TAF, and TFV
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). AUCtau for ATV (Cohorts 1 Part A, 2, 3, and 4 [Groups 2 to 4]); DRV (Cohorts 1 Part A, 2, and 3); TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 [Groups 1 to 3] taking F/TAF); and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 [Groups 1 to 3] taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) Through Week 24
Time Frame
First dose date up to Week 24 plus 30 days (Cumulative data through Week 24)
Title
Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities Through Week 24
Time Frame
First dose date up to Week 24 plus 30 days (Cumulative data through Week 24)
Secondary Outcome Measure Information:
Title
PK Parameter: Ctau of ATV, DRV, TAF, and TFV
Description
Ctau is defined as the observed drug concentration at the end of the dosing interval. Ctau for ATV (cohorts 1, 2, 3, and 4 (Groups 2 to 4)), DRV (cohorts 1, 2, and 3), COBI (except Cohort 5), FTC and TFV (cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV
Description
Cmax is defined as the maximum observed concentration of drug. Cmax for ATV (Cohorts 1, 2, 3, and 4 [Groups 2 to 4]) and DRV (Cohorts 1, 2, and 3); for COBI (except Cohort 5); for TAF, FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
PK Parameter: CL/F of ATV, DRV, COBI, TAF, FTC and TFV
Description
CL/F is defined as the apparent oral clearance following administration of the drug. CL/F for ATV (Cohorts 1, 2, 3, and 4 [Groups 2 to 4]) and DRV (Cohorts 1, 2, and 3); for COBI (except Cohort 5); for TAF, FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
PK Parameter: Vz/F of COBI, TAF, FTC and TFV
Description
Vz/F is defined as the apparent volume of distribution of the drug. Vz/F for COBI (Except Cohort 5); for TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF); for FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
PK Parameter: AUCtau of COBI, FTC and TFV
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). AUCtau for COBI (Except Cohort 5); for FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
PK Parameter: AUClast of TAF, FTC and TFV
Description
AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. AUClast for TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF); for FTC and TFV (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
PK Parameter: Clast of TAF
Description
Clast is defined as the the last observed quantifiable concentration of the drug in plasma. Clast for TAF (Cohorts 2, 3, 4 [Groups 1 to 4] and 5 taking F/TAF) will be reported.
Time Frame
Predose on Day 1, and postdose up to Week 48
Title
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time Frame
First dose date up to Week 48 plus 30 days (Cumulative data through Week 48)
Title
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
Time Frame
First dose date up to Week 48 plus 30 days (Cumulative data through Week 48)
Title
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
Title
Percentage of Participants with HIV-1 RNA < 50 Copies/mL at Week 48 and as Defined by the US FDA-defined Snapshot Algorithm
Time Frame
Week 48
Title
Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 24
Time Frame
Baseline, Week 24
Title
Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 48
Time Frame
Baseline, Week 48
Title
Change from Baseline in Percentage of CD4+ Cells at Week 24
Time Frame
Baseline, Week 24
Title
Change from Baseline in Percentage of CD4+ Cells at Week 48
Time Frame
Baseline, Week 48
Title
Acceptability of COBI and F/TAF as Measured by Palatability Score
Time Frame
Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Weeks
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: HIV-1 infected, virologically suppressed males and females Age ≥ 4 weeks to < 18 years (according to requirements of enrolling Cohort). Body weight at screening ≥ 25 to < 40 kg (Cohort 2); ≥ 14 to < 25 kg (Cohort 3); ≥ 3 to < 25 kg (Cohort 4); ≥ 3 to < 14 kg (Cohort 5) Stable antiretroviral (ARV) regimen for a minimum of 3 months prior to the screening visit. Participants enrolled prior to implementation of Amendment 7: 2 NRTIs and ATV/r once daily or DRV/r once daily or twice daily. Participants enrolled after the implementation of Amendment 9: Cohorts 2, 3 and 4 (Group 1): 2 NRTIs plus a third agent per local prescribing guidelines. Participants will switch from their current third agent to ATV or DRV at Day 1. Participants taking DRV must be on once-daily dosing or must switch to once daily at or prior to Day 1. Cohort 4 (Group 1), participants may also switch their current third agent to LPV/r at Day 1. Participants will switch their NRTI backbone to F/TAF. Cohort 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3): 2 NRTIs plus a third agent per local prescribing guidelines or treatment naive. Participants on treatment will switch from their current third agent to ATV or LPV/r (Cohort 4 [Groups 2 to 4]), or to a third unboosted agent (Cohort 5 [Groups 1 to 3]). Participants will switch their NRTI backbone to F/TAF. Participants undergoing dose modifications to their ARV regimen for growth or switching medication formulations are considered to be on a stable ARV regimen. Documented plasma HIV-1 RNA for ≥ 3 months preceding the screening visit: Participants enrolled after the implementation of Amendment 9: For Cohorts 2, 3, and 4 (Group 1), virologically suppressed ≥ 3 months preceding the screening visit: HIV-1 RNA < 50 copies/mL on a stable regimen (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) For Cohorts 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3), on an ARV regimen irrespective of plasma HIV-1 RNA copies or treatment naive; a participant is considered treatment naive if ARVs were given for prevention of mother-to-child transmission but not for HIV treatment For virologically suppressed participants, unconfirmed virologic elevations of HIV-1 RNA ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL (eg, < 20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on 2 consecutive HIV-1 RNA tests. Adequate renal function: Estimated Glomerular Filtration Rate (eGFR) ≥ 90 mL/min/1.73m2 using the Schwartz formula. If ≥ 1 year old, eGFR greater than or equal to the minimum normal value for age using the Schwartz Formula. If < 1 year old as follows: Age Minimum Value for eGFR (mL/min/1.73 m2) > 28 days to ≤ 95 days 30, ≥ 96 days to ≤ 6 months 39, > 6 to < 12 months 49 Participants must not have documented or suspected resistance to applicable study drugs including FTC, TFV, ATV, DRV, or LPV. Participants < 14 kg (Cohorts 4 [Groups 2 to 4] and 5 [Groups 1 to 3]) with M184V/I AND HIV-1 RNA < 50 copies/mL will be allowed. Positive confirmatory HIV test (confirmatory nucleic acid-based testing if < 18 months of age). Cohort 4 (Groups 2 to 4) and Cohort 5 (Groups 1 to 3): Last dose of nevirapine or efavirenz, if applicable, ≥ 14 days prior to enrollment. Note: Other protocol defined Inclusion/Exclusion criteria do apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gilead Study Team
Email
GSUS2160128@gilead.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Pediatric Infectious Disease Associates
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Individual Site Status
Completed
Facility Name
Jeffrey Goodman Special Care Clinic
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Withdrawn
Facility Name
Peter Morton Medical Building
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Completed
Facility Name
The George Washington University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Completed
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Individual Site Status
Completed
Facility Name
Emory-Children's Center- Ponce Family and Youth Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Individual Site Status
Withdrawn
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Individual Site Status
Withdrawn
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Withdrawn
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Withdrawn
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Individual Site Status
Completed
Facility Name
University of Texas Health Science Center of Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Completed
Facility Name
Hospital General de Agudos Cosme Argerich
City
Buenos Aires
ZIP/Postal Code
1151
Country
Argentina
Individual Site Status
Completed
Facility Name
Fundacion Huesped
City
Buenos Aires
ZIP/Postal Code
1202
Country
Argentina
Individual Site Status
Withdrawn
Facility Name
Helios Salud
City
Buenos Aires
ZIP/Postal Code
C1141 ACG
Country
Argentina
Individual Site Status
Active, not recruiting
Facility Name
Hospital Jose Maria Ramos Mejia
City
Buenos Aires
ZIP/Postal Code
C1221ADC
Country
Argentina
Individual Site Status
Withdrawn
Facility Name
Hopital del Nino
City
Panama City
ZIP/Postal Code
0816-00383
Country
Panama
Individual Site Status
Withdrawn
Facility Name
University of the Free State
City
Bloemfontein
ZIP/Postal Code
9300
Country
South Africa
Individual Site Status
Completed
Facility Name
University of Stellenbosch
City
Cape Town
ZIP/Postal Code
7505
Country
South Africa
Individual Site Status
Recruiting
Facility Name
Dr. J. Fourie Medical Practice
City
Dundee
ZIP/Postal Code
3000
Country
South Africa
Individual Site Status
Withdrawn
Facility Name
King Edward VIII Hospital
City
Durban
ZIP/Postal Code
3629
Country
South Africa
Individual Site Status
Recruiting
Facility Name
Rahima Moosa Mother and Child Hospital
City
Johannesburg
ZIP/Postal Code
2093
Country
South Africa
Individual Site Status
Recruiting
Facility Name
Be Part Yoluntu Centre
City
Paarl
ZIP/Postal Code
7626
Country
South Africa
Individual Site Status
Withdrawn
Facility Name
The Aurum Institute: Pretoria Clinical Research Centre
City
Pretoria
ZIP/Postal Code
87
Country
South Africa
Individual Site Status
Recruiting
Facility Name
Perinatal HIV Research Unit
City
Soweto
ZIP/Postal Code
2013
Country
South Africa
Individual Site Status
Recruiting
Facility Name
HIV-NAT
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Individual Site Status
Recruiting
Facility Name
Siriraj Hospital
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Individual Site Status
Recruiting
Facility Name
Srinagarind Hospital
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Individual Site Status
Completed
Facility Name
Queen Savang Vadhana Memorial Hospital
City
Sriracha
ZIP/Postal Code
20110
Country
Thailand
Individual Site Status
Withdrawn
Facility Name
MU-JHU Research Collaboration/MU-JHU Care Ltd
City
Kampala
ZIP/Postal Code
256
Country
Uganda
Individual Site Status
Not yet recruiting
Facility Name
Imperial College Healthcare NHS Trust
City
London
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Individual Site Status
Completed
Facility Name
University of Zimbabwe Clinical Research Centre
City
Harare
Country
Zimbabwe
Individual Site Status
Recruiting

12. IPD Sharing Statement

Links:
URL
https://www.gileadclinicaltrials.com/study/?id=GS-US-216-0128
Description
Gilead Clinical Trials Website

Learn more about this trial

Study of Cobicistat-Boosted Atazanavir (ATV/co), Cobicistat-Boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in Children With HIV

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