Acquired Immune Deficiency Syndrome (AIDS), HIV Infections
Conditions
Keywords
Pediatrics, Adolescents, HIV, HIV-1, Treatment experienced
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.
Interventions
DRUGATV
Capsules administered once daily according to dosing recommendations per product monograph
DRUGDRV
Tablets administered once daily according to dosing recommendations per product monograph
DRUGCobicistat
Tablets administered orally once daily with food
DRUGBR
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).
DRUGF/TAF
Tablets administered orally once daily
DRUGLPV/r
Solution administered orally
DRUGThird Unboosted Drug
ATV (administered orally), DRV (administered orally), and LPV/r (administered orally) would be general list but unspecified for sites.
DRUGCobicistat TOS
Tablets for oral suspension
DRUGF/TAF TOS
Tablets for oral suspension
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Weeks to 17 Years
Healthy volunteers
No
Inclusion 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 nucleoside reverse transcriptase inhibitors (NRTIs) and ritonavir-boosted atazanavir (ATV/r) once daily or ritonavir-boosted darunavir (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 darunavir (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 lopinavir boosted with ritonavir (LPV/r) at Day 1. Participants will switch their NRTI backbone to emtricitabine/tenofovir alafenamide (coformulated; Descovy®) (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 human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (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 is 30, ≥ 96 days to ≤ 6 months is 39, \> 6 to \< 12 months is 49. * Participants must not have documented or suspected resistance to applicable study drugs including emtricitabine (Emtriva®) (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, TAF, and TFV | Predose on Day 1, and postdose up to Week 48 | 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 | First dose date up to Week 24 plus 30 days (Cumulative data through Week 24) | — |
| Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities Through Week 24 | First dose date up to Week 24 plus 30 days (Cumulative data through Week 24) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Ctau of ATV, DRV, COBI, FTC and TFV | Predose on Day 1, and postdose up to Week 48 | 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 | Predose on Day 1, and postdose up to Week 48 | 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 | Predose on Day 1, and postdose up to Week 48 | 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 | Predose on Day 1, and postdose up to Week 48 | 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 and FTC | Predose on Day 1, and postdose up to Week 48 | 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) and FTC will be reported. |
| PK Parameter: AUClast of TAF, FTC and TFV | Predose on Day 1, and postdose up to Week 48 | 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 | Predose on Day 1, and postdose up to Week 48 | 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) | First dose date up to Week 48 plus 30 days (Cumulative data through Week 48) | — |
| Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values | First dose date up to Week 48 plus 30 days (Cumulative data through Week 48) | — |
| Percentage of Participants with HIV-1 RNA < 50 Copies/mL at Week 24 and as Defined by the US FDA-defined Snapshot Algorithm | Week 24 | — |
| Percentage of Participants with HIV-1 RNA < 50 Copies/mL at Week 48 and as Defined by the US FDA-defined Snapshot Algorithm | Week 48 | — |
| Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 24 | Baseline, Week 24 | — |
| Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 48 | Baseline, Week 48 | — |
| Change from Baseline in Percentage of CD4+ Cells at Week 24 | Baseline, Week 24 | — |
| Change from Baseline in Percentage of CD4+ Cells at Week 48 | Baseline, Week 48 | — |
| Acceptability of COBI and F/TAF as Measured by Palatability Score | Week 48 | — |
Countries
Argentina, South Africa, Thailand, Uganda, United Kingdom, United States, Zimbabwe
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed