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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 133
- 试验地点
- 23
- 主要终点
- Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) Through Week 24
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Weeks 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Participants taking DRV must be on once-daily dosing or must switch to once daily at or prior to Day
- •Cohort 4 (Group 1), participants may also switch their current third agent to lopinavir boosted with ritonavir (LPV/r) at Day
- •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
- •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/
排除标准
- 未提供
研究组 & 干预措施
Cohort 3
Participants age ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
干预措施: F/TAF (Drug)
Cohort 4 (Group 1)
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.
干预措施: LPV/r (Drug)
Cohort 4 (Group 3)
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.
干预措施: ATV (Drug)
Cohort 4 (Group 3)
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.
干预措施: Cobicistat TOS (Drug)
Cohort 5 (Group 2)
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.
干预措施: F/TAF TOS (Drug)
Cohort 5 (Group 1)
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.
干预措施: Third Unboosted Drug (Drug)
Cohort 5 (Group 3)
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.
干预措施: F/TAF TOS (Drug)
Cohort 4 (Group 3)
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.
干预措施: LPV/r (Drug)
Cohort 4 (Group 3)
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.
干预措施: F/TAF TOS (Drug)
Cohort 4 (Group 4)
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.
干预措施: ATV (Drug)
Cohort 4 (Group 4)
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.
干预措施: LPV/r (Drug)
Cohort 5 (Group 3)
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.
干预措施: Third Unboosted Drug (Drug)
Cohort 4 (Group 2)
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.
干预措施: Cobicistat TOS (Drug)
Cohort 2
Participants aged 6 to <12 years old and ≥25 to <40kg will receive cobicistat 150 mg and F/TAF 200/25 mg with either ATV or DRV.
干预措施: ATV (Drug)
Cohort 2
Participants aged 6 to <12 years old and ≥25 to <40kg will receive cobicistat 150 mg and F/TAF 200/25 mg with either ATV or DRV.
干预措施: F/TAF (Drug)
Cohort 4 (Group 4)
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.
干预措施: Cobicistat TOS (Drug)
Cohort 3
Participants age ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
干预措施: ATV (Drug)
Cohort 1: Part A and Part B
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.
干预措施: ATV (Drug)
Cohort 2
Participants aged 6 to <12 years old and ≥25 to <40kg will receive cobicistat 150 mg and F/TAF 200/25 mg with either ATV or DRV.
干预措施: DRV (Drug)
Cohort 4 (Group 1)
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.
干预措施: ATV (Drug)
Cohort 4 (Group 2)
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.
干预措施: ATV (Drug)
Cohort 1: Part A and Part B
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.
干预措施: DRV (Drug)
Cohort 1: Part A and Part B
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.
干预措施: BR (Drug)
Cohort 3
Participants age ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
干预措施: DRV (Drug)
Cohort 4 (Group 1)
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.
干预措施: DRV (Drug)
Cohort 4 (Group 1)
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.
干预措施: F/TAF TOS (Drug)
Cohort 4 (Group 2)
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.
干预措施: LPV/r (Drug)
Cohort 4 (Group 2)
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.
干预措施: F/TAF TOS (Drug)
Cohort 4 (Group 1)
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.
干预措施: Cobicistat TOS (Drug)
Cohort 5 (Group 1)
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.
干预措施: F/TAF TOS (Drug)
Cohort 5 (Group 2)
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.
干预措施: Third Unboosted Drug (Drug)
Cohort 4 (Group 4)
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.
干预措施: F/TAF TOS (Drug)
Cohort 1: Part A and Part B
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.
干预措施: Cobicistat (Drug)
Cohort 2
Participants aged 6 to <12 years old and ≥25 to <40kg will receive cobicistat 150 mg and F/TAF 200/25 mg with either ATV or DRV.
干预措施: Cobicistat (Drug)
Cohort 3
Participants age ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.
干预措施: Cobicistat (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) Through Week 24
时间窗: First dose date up to Week 24 plus 30 days (Cumulative data through Week 24)
Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, TAF, and TFV
时间窗: 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 Laboratory Abnormalities Through Week 24
时间窗: First dose date up to Week 24 plus 30 days (Cumulative data through Week 24)
次要结局
- PK Parameter: Clast of TAF(Predose on Day 1, and postdose up to Week 48)
- PK Parameter: Vz/F of COBI, TAF, FTC and TFV(Predose on Day 1, and postdose up to Week 48)
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)(First dose date up to Week 48 plus 30 days (Cumulative data through Week 48))
- Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 48(Baseline, Week 48)
- PK Parameter: Ctau of ATV, DRV, COBI, FTC and TFV(Predose on Day 1, and postdose up to Week 48)
- PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV(Predose on Day 1, and postdose up to 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)
- Acceptability of COBI and F/TAF as Measured by Palatability Score(Week 48)
- Change from Baseline in Percentage of CD4+ Cells at Week 24(Baseline, Week 24)
- PK Parameter: CL/F of ATV, DRV, COBI, TAF, FTC and TFV(Predose on Day 1, and postdose up to Week 48)
- Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 24(Baseline, Week 24)
- PK Parameter: AUCtau of COBI and FTC(Predose on Day 1, and postdose up to Week 48)
- PK Parameter: AUClast of TAF, FTC and TFV(Predose on Day 1, and postdose up to 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))
- Change from Baseline in Percentage of CD4+ Cells at Week 48(Baseline, Week 48)