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

Gilead Sciences

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Acquired Immune Deficiency Syndrome (AIDS); HIV Infections

Treatments: Drug: LPV/r; Drug: ATV; Drug: Cobicistat; Drug: F/TAF TOS; Drug: F/TAF; Drug: Cobicistat TOS; Drug: Third Unboosted Drug; Drug: BR; Drug: DRV

Study type: Interventional

Funder types: Industry

Identifiers

NCT02016924

2013-001402-28 (EudraCT Number)

GS-US-216-0128

Details and patient eligibility

About

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.

Enrollment: 130 estimated patients

Sex: All

Ages: 4 weeks to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 10 patient groups

Cohort 1: Part A and Part B

Experimental group

Description:

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.

Treatment:

Drug: DRV

Drug: BR

Drug: Cobicistat

Drug: ATV

Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: DRV

Drug: F/TAF

Drug: Cobicistat

Drug: ATV

Cohort 3

Experimental group

Description:

Participants age ≥ 2 years old will receive cobicistat 90 mg and F/TAF 120/15 mg with either ATV or DRV.

Treatment:

Drug: DRV

Drug: F/TAF

Drug: Cobicistat

Drug: ATV

Cohort 4 (Group 1)

Experimental group

Description:

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.

Treatment:

Drug: DRV

Drug: Cobicistat TOS

Drug: F/TAF TOS

Drug: ATV

Drug: LPV/r

Cohort 4 (Group 2)

Experimental group

Description:

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.

Treatment:

Drug: Cobicistat TOS

Drug: F/TAF TOS

Drug: ATV

Drug: LPV/r

Cohort 4 (Group 3)

Experimental group

Description:

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.

Treatment:

Drug: Cobicistat TOS

Drug: F/TAF TOS

Drug: ATV

Drug: LPV/r

Cohort 4 (Group 4)

Experimental group

Description:

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.

Treatment:

Drug: Cobicistat TOS

Drug: F/TAF TOS

Drug: ATV

Drug: LPV/r

Cohort 5 (Group 1)

Experimental group

Description:

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.

Treatment:

Drug: Third Unboosted Drug

Drug: F/TAF TOS

Cohort 5 (Group 2)

Experimental group

Description:

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.

Treatment:

Drug: Third Unboosted Drug

Drug: F/TAF TOS

Cohort 5 (Group 3)

Experimental group

Description:

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.

Treatment:

Drug: Third Unboosted Drug

Drug: F/TAF TOS