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

Sponsor

Gilead Sciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02016924

Collaborator

(none)

100

Enrollment

Locations

Arms

146.5

Anticipated Duration (Months)

3.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 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 < 35 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 < 35 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 < 35 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 (≥ 3 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 (≥ 3 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 (≥ 3 years of age)

Condition or Disease	Intervention/Treatment	Phase
Acquired Immune Deficiency Syndrome (AIDS) HIV Infections	Drug: ATV Drug: DRV Drug: Cobicistat Drug: BR	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 16, 2014

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A, Cohort 1 Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus 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.	Drug: ATV Capsules administered once daily according to dosing recommendations per product monograph Other Names: Reyataz® Drug: DRV Tablets administered once daily according to dosing recommendations per product monograph Other Names: Prezista® Drug: Cobicistat Tablets administered orally once daily with food Other Names: GS-9350 Tybost® Drug: BR Prior to implementation protocol amendment 7, Background Regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). After implementation of protocol amendment 7, BR must include 2 NRTIs and a third agent per local prescribing guidelines.
Experimental: Cohort 2 Participants ages 6 to <12 years old will receive cobicistat 150 mg and emtricitabine/tenofovir alafenamide 200/25 mg with either ATV or DRV.	Drug: ATV Capsules administered once daily according to dosing recommendations per product monograph Other Names: Reyataz® Drug: DRV Tablets administered once daily according to dosing recommendations per product monograph Other Names: Prezista® Drug: Cobicistat Tablets administered orally once daily with food Other Names: GS-9350 Tybost®
Experimental: Cohort 3 Participants ages ≥ 3 will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.	Drug: ATV Capsules administered once daily according to dosing recommendations per product monograph Other Names: Reyataz® Drug: DRV Tablets administered once daily according to dosing recommendations per product monograph Other Names: Prezista® Drug: Cobicistat Tablets administered orally once daily with food Other Names: GS-9350 Tybost®
Experimental: Part B, Cohort 1 Participants ages 12 to <18 years old will receive cobicistat 150 mg with either ATV or DRV plus 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.	Drug: ATV Capsules administered once daily according to dosing recommendations per product monograph Other Names: Reyataz® Drug: DRV Tablets administered once daily according to dosing recommendations per product monograph Other Names: Prezista® Drug: Cobicistat Tablets administered orally once daily with food Other Names: GS-9350 Tybost® Drug: BR Prior to implementation protocol amendment 7, Background Regimen (BR) must include 2 nucleoside reverse transcriptase inhibitors (NRTI). After implementation of protocol amendment 7, BR must include 2 NRTIs and a third agent per local prescribing guidelines.

Outcome Measures

Primary Outcome Measures

Pharmacokinetic (PK) Parameter: AUCtau of ATV and DRV [Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10]
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, and TAF for Cohorts 2 and 3 [Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4]
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Treatment Emergent Laboratory Abnormalities Through Week 24 [First dose date and up to 24 weeks plus 30 days]

Secondary Outcome Measures

PK Parameter: Ctau of ATV, DRV, and COBI for Cohort 1 [Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).]
Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Cmax of ATV, DRV, and COBI for Cohort 1 [Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).]
Cmax is defined as the maximum observed concentration of drug.
PK Parameter: CL/F of ATV, DRV, and COBI for Cohort 1 [Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).]
CL/F is defined as the apparent oral clearance following administration of the drug.
PK Parameter: Vz/F of COBI for Cohort 1 [Intensive PK samples at Predose, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10. Trough PK samples at Day 1 prior to adminstering COBI and at Weeks 12, 24, and 48 (Part A), or at Weeks 4, 12, 24, 32, and 48 (Part B).]
Vz/F is defined as the apparent volume of distribution of the drug.
PK Parameter: Ctau of ATV, DRV, COBI, FTC, and TFV for Cohorts 2 and 3 [Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48]
Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV for Cohorts 2 and 3 [Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48]
Cmax is defined as the maximum observed concentration of drug.
PK Parameter: CL/F of ATV, DRV, and TAF for Cohorts 2 and 3 [Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48]
CL/F is defined as the apparent oral clearance following administration of the drug.
PK Parameter: Vz/F of COBI and TAF for Cohorts 2 and 3 [Intensive PK samples at Predose 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Week 2 or Week 4. Trough PK samples at Weeks 8, 24, and 36, and timed PK samples (15 minutes to 3 hours post-dose) at Weeks 12, 16, and 48]
Vz/F is defined as the apparent volume of distribution of the drug.
The incidence of treatment-emergent AEs and treatment-emergent laboratory abnormalities through Week 48 [Up to 48 weeks plus 30 days]
The 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]
The change from baseline in CD4+ cell counts [Week 24]
The change from baseline in CD4+ cell counts [Week 48]
The change from baseline in CD4+ percentages [Week 24]
The change from baseline in CD4+ percentages [Week 48]
Acceptability of COBI and F/TAF as Measured by Palatability [Day 1, and at Weeks 4 (Day 10 for Cohort 1 Part A), 24 and 48.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

HIV-1 infected treatment-experienced, virologically suppressed males and females aged 3 years to < 18 years at the Day 1 visit (according to requirements of enrolling Cohort)
Body weight at screening ≥ 25 kg (Cohorts 1), 14 kg to < 25 kg (Cohort 3)
Stable antiretroviral regimen including 2 nucleoside reverse transcriptase inhibitors and either ritonavir-boosted atazanavir or ritonavir-boosted darunavir once or twice daily as per product label for a minimum of 3 months prior to the screening visit. Treatment-experienced pediatric individuals taking DRV/r must have no history of DRV resistance associated mutations.
Documented negative screening for active pulmonary tuberculosis (TB) per local standard of care within 6 months of a screening visit

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pediatric Infectious Disease Associates	Long Beach	California	United States	90806
2	Jeffrey Goodman Special Care Clinic	Los Angeles	California	United States	90027
3	Peter Morton Medical Building	Los Angeles	California	United States	90095
4	University of Colorado Denver	Aurora	Colorado	United States	80045
5	The George Washington University	Washington	District of Columbia	United States	20010
6	University of South Florida	Tampa	Florida	United States	33606
7	Emory-Children's Center- Ponce Family and Youth Clinic	Atlanta	Georgia	United States	30308
8	Boston University Medical Center	Boston	Massachusetts	United States	02118
9	New York University School of Medicine	New York	New York	United States	10016
10	SUNY Upstate Medical University	Syracuse	New York	United States	13210
11	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
12	University of Texas Health Science Center of Houston	Houston	Texas	United States	77030
13	Hospital General de Agudos Cosme Argerich	Buenos Aires		Argentina	1151
14	Fundacion Huesped	Buenos Aires		Argentina	1202
15	Helios Salud	Buenos Aires		Argentina	C1141 ACG
16	Hospital Jose Maria Ramos Mejia	Buenos Aires		Argentina	C1221ADC
17	Hopital del Nino	Panama City		Panama	0816-00383
18	University of the Free State	Bloemfontein		South Africa	9300
19	University of Stellenbosch	Cape Town		South Africa	7505
20	Dr. J. Fourie Medical Practice	Dundee		South Africa	3000
21	Rahima Moosa Mother and Child Hospital	Johannesburg		South Africa	2093
22	Be Part Yoluntu Centre	Paarl		South Africa	7626
23	The Aurum Institute: Pretoria Clinical Research Centre	Pretoria		South Africa	87
24	Perinatal HIV Research Unit	Soweto		South Africa	2013
25	HIV-NAT	Bangkok		Thailand	10330
26	Siriraj Hospital	Bangkok		Thailand	10700
27	Srinagarind Hospital	Khon Kaen		Thailand	40002
28	Queen Savang Vadhana Memorial Hospital	Sriracha		Thailand	20110
29	Imperial College Healthcare NHS Trust	London		United Kingdom	W2 1NY
30	University of Zimbabwe Clinical Research Centre	Harare		Zimbabwe