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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02016924
• Other study ID #: GS-US-216-0128
• Secondary ID: 2013-001402-28
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 16, 2014
• Est. completion date: March 2027

Study information

• Verified date: June 2024
• Source: Gilead Sciences
• Contact: Gilead Study Team
• Email: GSUS2160128[@]gilead.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: March 2027
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Weeks to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immune Deficiency Syndrome (AIDS)
• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• ATV
Capsules administered once daily according to dosing recommendations per product monograph
• DRV
Tablets administered once daily according to dosing recommendations per product monograph
• Cobicistat
Tablets administered orally once daily with food
• 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).
• F/TAF
Tablets administered orally once daily
• LPV/r
Solution administered orally
• Third Unboosted Drug
ATV (administered orally), DRV (administered orally), and LPV/r (administered orally) would be general list but unspecified for sites.
• Cobicistat TOS
Tablets for oral suspension
• F/TAF TOS
Tablets for oral suspension

Locations

Country	Name	City	State
Argentina	Fundacion Huesped	Buenos Aires
Argentina	Helios Salud	Buenos Aires
Argentina	Hospital General de Agudos Cosme Argerich	Buenos Aires
Argentina	Hospital Jose Maria Ramos Mejia	Buenos Aires
Panama	Hopital del Nino	Panama City
South Africa	University of the Free State	Bloemfontein
South Africa	University of Stellenbosch	Cape Town
South Africa	Dr. J. Fourie Medical Practice	Dundee
South Africa	King Edward VIII Hospital	Durban
South Africa	VIDA-Nkanyezi	Johannesburg
South Africa	Be Part Yoluntu Centre	Paarl
South Africa	The Aurum Institute: Pretoria Clinical Research Centre	Pretoria
South Africa	Perinatal HIV Research Unit	Soweto
Thailand	HIV-NAT	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Srinagarind Hospital	Khon Kaen
Thailand	Queen Savang Vadhana Memorial Hospital	Sriracha
Uganda	MU-JHU Research Collaboration/MU-JHU Care Ltd	Kampala
Uganda	SICRA-TASO Mulago National Referral Hospital	Kampala
Uganda	AMBSO Masaka Clinical Research Site	Masaka
United Kingdom	Imperial College Healthcare NHS Trust	London
United States	Emory-Children's Center- Ponce Family and Youth Clinic	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Boston University Medical Center	Boston	Massachusetts
United States	University of Texas Health Science Center of Houston	Houston	Texas
United States	Pediatric Infectious Disease Associates	Long Beach	California
United States	Jeffrey Goodman Special Care Clinic	Los Angeles	California
United States	Peter Morton Medical Building	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	New York University School of Medicine	New York	New York
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of South Florida	Tampa	Florida
United States	The George Washington University	Washington	District of Columbia
Zimbabwe	University of Zimbabwe Clinical Research Centre	Harare

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Zimbabwe,  Argentina,  Panama,  South Africa,  Thailand,  Uganda,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)		First dose date up to Week 48 plus 30 days (Cumulative data through Week 48)
Secondary	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)
Secondary	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
Secondary	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
Secondary	Change from Baseline in CD4+ Cell Counts (cells/µL) at Week 24		Baseline, Week 24
Secondary	Change from Baseline in CD4+ Cell Counts (cells/µL) at Week 48		Baseline, Week 48
Secondary	Change from Baseline in Percentage of CD4+ Cells at Week 24		Baseline, Week 24
Secondary	Change from Baseline in Percentage of CD4+ Cells at Week 48		Baseline, Week 48
Secondary	Acceptability of COBI and F/TAF as Measured by Palatability Score		Week 48

External Links

•   Gilead Clinical Trials Website