Clinical trial NCT02016924: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acquired Immune Deficiency Syndrome (AIDS)
HIV Infections
Keywords: Pediatrics
Adolescents
HIV
HIV-1
Treatment experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-12-20
Enrollment: 133
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUCtau of ATV, DRV, TAF, and TFV
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) Through Week 24
timeFrame: First dose date up to Week 24 plus 30 days (Cumulative data through Week 24)
measure: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities Through Week 24
timeFrame: First dose date up to Week 24 plus 30 days (Cumulative data through Week 24)
Secondary outcomes:
measure: PK Parameter: Ctau of ATV, DRV, COBI, FTC and TFV
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: PK Parameter: Cmax of ATV, DRV, COBI, TAF, FTC and TFV
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: PK Parameter: CL/F of ATV, DRV, COBI, TAF, FTC and TFV
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: PK Parameter: Vz/F of COBI, TAF, FTC and TFV
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: PK Parameter: AUCtau of COBI and FTC
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: PK Parameter: AUClast of TAF, FTC and TFV
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: PK Parameter: Clast of TAF
timeFrame: Predose on Day 1, and postdose up to Week 48
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose date up to Week 48 plus 30 days (Cumulative data through Week 48)
measure: Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values
timeFrame: First dose date up to Week 48 plus 30 days (Cumulative data through Week 48)
measure: Percentage of Participants with HIV-1 RNA < 50 Copies/mL at Week 24 and as Defined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 24
measure: Percentage of Participants with HIV-1 RNA < 50 Copies/mL at Week 48 and as Defined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 48
measure: Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in CD4+ Cell Counts (cells/μL) at Week 48
timeFrame: Baseline, Week 48
measure: Change from Baseline in Percentage of CD4+ Cells at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in Percentage of CD4+ Cells at Week 48
timeFrame: Baseline, Week 48
measure: Acceptability of COBI and F/TAF as Measured by Palatability Score
timeFrame: Week 48
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Pediatric Infectious Disease Associates
state: California
city: Los Angeles
country: United States
facility: Peter Morton Medical Building
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center of Houston
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos Cosme Argerich
city: Buenos Aires
country: Argentina
facility: Helios Salud
city: Bloemfontein
country: South Africa
facility: University of the Free State
city: Cape Town
country: South Africa
facility: University of Stellenbosch
city: Durban
country: South Africa
facility: King Edward VIII Hospital
city: Johannesburg
country: South Africa
facility: Rahima Clinical Trials, a Division of Wits Health Consortium (Pty) Ltd
city: Pretoria
country: South Africa
facility: The Aurum Institute: Pretoria Clinical Research Centre
city: Soweto
country: South Africa
facility: Perinatal HIV Research Unit
city: Bangkok
country: Thailand
facility: HIV-NAT
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Kampala
country: Uganda
facility: MU-JHU Research Collaboration/MU-JHU Care Ltd
city: Kampala
country: Uganda
facility: SICRA-TASO Mulago National Referral Hospital
city: Masaka
country: Uganda
facility: AMBSO Masaka Clinical Research Site
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Harare
country: Zimbabwe
facility: University of Zimbabwe Clinical Research Centre
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: