Study of Cobicistat-Boosted Atazanavir (ATV/co), Cobicistat-Boosted Darunavir (DRV/co) and Emtricitabine/Tenofovir Alafenamide (F/TAF) in Children With HIV

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

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.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections; Acquired Immune Deficiency Syndrome (AIDS)
• Intervention / Treatment: Drug: ATV; Drug: DRV; Drug: Cobicistat; Drug: BR; Drug: F/TAF; Drug: LPV/r; Drug: Cobicistat TOS; Drug: F/TAF TOS; Drug: Third Unboosted Drug

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Gilead Study Team; Email: GSUS2160128@gilead.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1202
    • Withdrawn
    • Fundación Huésped
  • Buenos Aires, Argentina, C1221ADC
    • Withdrawn
    • Hospital Jose Maria Ramos Mejia
  • Buenos Aires, Argentina, 1151
    • Completed
    • Hospital General de Agudos Cosme Argerich
  • Buenos Aires, Argentina, C1141 ACG
    • Active, not recruiting
    • Helios Salud
• Panama
  • Panama City, Panama, 0816-00383
    • Withdrawn
    • Hopital del Nino
• South Africa
  • Bloemfontein, South Africa, 9300
    • Completed
    • University of The Free State
  • Cape Town, South Africa, 7505
    • Recruiting
    • University of Stellenbosch
  • Dundee, South Africa, 3000
    • Withdrawn
    • Dr. J. Fourie Medical Practice
  • Durban, South Africa, 3629
    • Recruiting
    • King Edward VIII Hospital
  • Johannesburg, South Africa, 2093
    • Recruiting
    • Rahima Moosa Mother and Child Hospital
  • Paarl, South Africa, 7626
    • Withdrawn
    • Be Part Yoluntu Centre
  • Pretoria, South Africa, 87
    • Recruiting
    • The Aurum Institute: Pretoria Clinical Research Centre
  • Soweto, South Africa, 2013
    • Recruiting
    • Perinatal HIV Research Unit
• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Siriraj Hospital
  • Bangkok, Thailand, 10330
    • Recruiting
    • HIV-NAT
  • Khon Kaen, Thailand, 40002
    • Completed
    • Srinagarind Hospital
  • Sriracha, Thailand, 20110
    • Withdrawn
    • Queen Savang Vadhana Memorial Hospital
• Uganda
  • Kampala, Uganda, 256
    • Not yet recruiting
    • MU-JHU Research Collaboration/MU-JHU Care Ltd
• United Kingdom
  • London, United Kingdom, W2 1NY
    • Completed
    • Imperial College Healthcare NHS Trust
• United States
  • California
    • Long Beach, California, United States, 90806
      • Completed
      • Pediatric Infectious Disease Associates
    • Los Angeles, California, United States, 90027
      • Withdrawn
      • Jeffrey Goodman Special Care Clinic
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • Peter Morton Medical Building
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Completed
      • University of Colorado Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Completed
      • The George Washington University
  • Florida
    • Tampa, Florida, United States, 33606
      • Completed
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Withdrawn
      • Emory-Children's Center- Ponce Family and Youth Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Withdrawn
      • Boston University Medical Center
  • New York
    • New York, New York, United States, 10016
      • Withdrawn
      • New York University School of Medicine
    • Syracuse, New York, United States, 13210
      • Withdrawn
      • SUNY Upstate Medical University
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Active, not recruiting
      • St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Completed
      • University of Texas Health Science Center of Houston
• Zimbabwe
  • Harare, Zimbabwe
    • Recruiting
    • University of Zimbabwe Clinical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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: Tybost®; GS-9350; Drug: 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).
Experimental: 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.	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: LPV/r; Solution administered orally; Drug: Cobicistat TOS; Tablets for oral suspension; Other Names: Tybost®; GS-9350; Drug: F/TAF TOS; Tablets for oral suspension; Other Names: Descovy®
Experimental: 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.	Drug: ATV; Capsules administered once daily according to dosing recommendations per product monograph; Other Names: Reyataz®; Drug: LPV/r; Solution administered orally; Drug: Cobicistat TOS; Tablets for oral suspension; Other Names: Tybost®; GS-9350; Drug: F/TAF TOS; Tablets for oral suspension; Other Names: Descovy®
Experimental: 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.	Drug: ATV; Capsules administered once daily according to dosing recommendations per product monograph; Other Names: Reyataz®; Drug: LPV/r; Solution administered orally; Drug: Cobicistat TOS; Tablets for oral suspension; Other Names: Tybost®; GS-9350; Drug: F/TAF TOS; Tablets for oral suspension; Other Names: Descovy®
Experimental: 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.	Drug: ATV; Capsules administered once daily according to dosing recommendations per product monograph; Other Names: Reyataz®; Drug: LPV/r; Solution administered orally; Drug: Cobicistat TOS; Tablets for oral suspension; Other Names: Tybost®; GS-9350; Drug: F/TAF TOS; Tablets for oral suspension; Other Names: Descovy®
Experimental: 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.	Drug: F/TAF TOS; Tablets for oral suspension; Other Names: Descovy®; Drug: Third Unboosted Drug; ATV (administered orally), DRV (administered orally), and LPV/r (administered orally) would be general list but unspecified for sites.
Experimental: 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.	Drug: F/TAF TOS; Tablets for oral suspension; Other Names: Descovy®; Drug: Third Unboosted Drug; ATV (administered orally), DRV (administered orally), and LPV/r (administered orally) would be general list but unspecified for sites.
Experimental: 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.	Drug: F/TAF TOS; Tablets for oral suspension; Other Names: Descovy®; Drug: Third Unboosted Drug; ATV (administered orally), DRV (administered orally), and LPV/r (administered orally) would be general list but unspecified for sites.
Experimental: 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.	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: Tybost®; GS-9350; Drug: F/TAF; Tablets administered orally once daily; Other Names: Descovy®
Experimental: Cohort 3; Participants age ≥ 2 years old 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: Tybost®; GS-9350; Drug: F/TAF; Tablets administered orally once daily; Other Names: Descovy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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.	Predose on Day 1, and postdose up to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
PK Parameter: Ctau of ATV, DRV, COBI, FTC 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.	Predose on Day 1, and postdose up to Week 48
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.	Predose on Day 1, and postdose up to Week 48
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.	Predose on Day 1, and postdose up to Week 48
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.	Predose on Day 1, and postdose up to Week 48
PK Parameter: AUCtau of COBI and FTC	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.	Predose on Day 1, and postdose up to Week 48
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.	Predose on Day 1, and postdose up to Week 48
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.	Predose on Day 1, and postdose up to Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2014
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 16, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (Estimated): December 20, 2013

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Adolescents; HIV; HIV-1; Pediatrics; Treatment experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Cobicistat
• Other Study ID Numbers: GS-US-216-0128; 2013-001402-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No