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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

About

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 human immunodeficiency virus-1 (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 pediatric participants weighing ≥ 25 to < 40 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 pediatric participants weighing ≥ 25 to < 40 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 pediatric participants weighing ≥ 25 to < 40 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 pediatric participants weighing ≥ 14 to < 25 kg (≥ 2 years of age) - To evaluate the steady-state PK of TAF and confirm the dose of F/TAF in HIV-1 infected pediatric participants weighing ≥ 14 to < 25 kg (≥ 2 years of age) - To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected pediatric participants weighing ≥ 14 to < 25 kg (≥ 2 years of age) Cohort 4: The primary objectives are: - To evaluate the steady-state PK of ATV and confirm the dose of ATV/co in HIV-1 infected pediatric participants weighing ≥ 5 to < 14 kg (≥ 3 months of age; Groups 2 to 4) - To evaluate the steady-state PK of TAF and confirm the dose of F/TAF in HIV-1 infected pediatric participants weighing ≥ 3 to < 14 kg (≥ 4 weeks of age; Groups 2 to 4) - To evaluate the safety and tolerability of ATV/co, DRV/co, and F/TAF through 24 weeks in HIV-1 infected pediatric participants weighing ≥ 3 to < 25 kg (≥ 4 weeks of age; Groups 1 to 4) Cohort 5: The primary objectives are: - To evaluate the steady-state PK of TAF and confirm the dose of F/TAF in HIV-1 infected pediatric participants on an unboosted third antiretroviral (ARV) regimen weighing ≥ 3 to < 14 kg (≥ 4 weeks of age) - To evaluate the safety and tolerability of F/TAF in combination with a third unboosted agent through 24 weeks in HIV-1 infected pediatric participants weighing ≥ 3 to < 14 kg (≥ 4 weeks of age)

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase II/III

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
4 Weeks
Maximum Age
17 Years

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
        • 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.

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Study Stats
Protocol No.
19-001980
Category
Pediatrics
Contact
Jaime Deville
Location
  • UCLA Westwood
For Providers
NCT No.
NCT02016924
For detailed technical eligibility, visit ClinicalTrials.gov.