Have you or your loved ones been diagnosed with acquired immune deficiency syndrome (aids)?
You may be eligible to participate in a acquired immune deficiency syndrome (aids) clinical trial.
Have you or your loved ones been diagnosed with acquired immune deficiency syndrome (aids)? You may be eligible to participate in a acquired immune deficiency syndrome (aids) clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Acquired Immune Deficiency Syndrome (AIDS) Clinical Trial
Have you or your loved ones been diagnosed with acquired immune deficiency syndrome (aids)?
You may be eligible to participate in a acquired immune deficiency syndrome (aids) clinical trial.
Have you or your loved ones been diagnosed with acquired immune deficiency syndrome (aids)? You may be eligible to participate in a acquired immune deficiency syndrome (aids) clinical trial.
Recruiting
Male & Female
4 - 17
Years old
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.
Details for the study
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
Brief Summary
The goal of this clinical study is to learn more about the safety and dosing of study drugs, <br /> cobicistat-boosted Atazanavir (ATV/co), cobicistat-boosted darunavir (DRV/co) and <br /> emtricitabine/tenofovir alafenamide (F/TAF), in children (age ≥ 4 weeks to < 18 years) with <br /> HIV.
Treatments and/or Procedures
Cobicistat
Tablets administered orally once daily with food
F TAF TOS
Tablets for oral suspension
Cobicistat TOS
Tablets for oral suspension
Third unboosted drug
ATV (administered orally), DRV (administered orally), and LPV/r (administered orally) would be general list but unspecified for sites.
LPV r
Solution administered orally
ATV
Capsules administered once daily according to dosing recommendations per product monograph
DRV
Tablets administered once daily according to dosing recommendations per product monograph
BR
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).
F TAF
Tablets administered orally once daily
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
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.
Secondary
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.
Secondary
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.
Secondary
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.
Secondary
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.
Secondary
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.
Secondary
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.
Secondary
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.
Study 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.