Clinical trial NCT02881320: Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination in Adolescents and Children With Human Immunodeficiency Virus-1
Official title: A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Fixed Dose Combination (FDC) in HIV-1 Infected Adolescents and Children
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-08-26
Enrollment: 177
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goals of this clinical study are to learn how Bictegravir/Emtricitabine/Tenofovir Alafenamide fixed dose combination (FDC) interacts with the body, confirm the dose, and also to learn more about the safety and tolerability of Bictegravir/Emtricitabine/Tenofovir Alafenamide FDC in adolescents and children with HIV-1.


Eligibility criteria: Key Inclusion Criteria:

Cohort 1: HIV-1 infected adolescents (12 to \< 18 years of age and screening weight ≥ 35 kg) who are virologically suppressed for ≥ 6 months prior to screening. Cohort 2: HIV-1 infected children (6 to \< 12 years of age and screening weight ≥ 25 kg) who are virologically suppressed for ≥ 6 months prior to screening.

Cohort 3: HIV-1 infected children (≥ 2 years of age and screening weight of ≥ 14 to \< 25 kg) who are virologically suppressed for ≥ 6 months prior to screening.

Cohort 4 Group 1: HIV-1 infected children (≥ 2 years of age and screening weight of ≥ 14 to \< 25 kg) who are virologically suppressed for ≥ 6 months prior to screening and unable to swallow tablets.

* Documented plasma HIV-1 ribonucleic acid (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 ≥ 6 months preceding the Screening visit. Unconfirmed virologic elevations of ≥ 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 two consecutive HIV-1 RNA tests.
* Stable antiretroviral regimen of 2 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third agent for a minimum of 6 months prior to the screening visit. Individuals undergoing dose modifications to their antiretroviral regimen for growth or who are switching medication formulation(s) are considered to be on a stable antiretroviral regimen.
* Estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m\^2 according to the Schwartz Formula.
* No documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), or integrase strand transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R and M184V/I.

Cohort 4 Group 2-4: HIV-1 infected children (≥ 1 month of age and screening weight of ≥ 3 to \< 14 kg) who are treatment naive or on antiretroviral (ARV) treatment for ≥ 1 month prior to screening.

* Positive confirmatory HIV test (confirmatory nucleic acid-based testing if \< 18 months of age).
* On a stable ARV regimen for ≥ 1 month or treatment naive (Individual is considered treatment naive if ARVs were given for prevention of mother-to-child transmission but not for HIV treatment).
* For \< 1 year of age, eGFR ≥ the minimum normal values for age according to the information below using the Schwartz Formula,

  * 30 mL/min/1.73 m\^2 for age \> 4 weeks to ≤ 95 days.
  * 39 mL/min/1.73 m\^2 for age ≥ 96 days to ≤ 6 months.
  * 49 mL/min/1.73 m\^2 for age \> 6 months to \< 12 months.
* For ≥ 1 year of age, eGFR ≥ 90 mL/min/1.73 m\^2 using the Schwartz Formula.
* No documented or suspected resistance to FTC, TFV, or INSTIs including, but not limited to, the reverse transcriptase resistance mutation K65R.
* For individuals \< 14 kg, M184V/I AND HIV-1 RNA \< 50 copies/mL will be allowed. Individuals with HIV-1 RNA \> 50 copies/mL should not have FTC, TFV, or INSTI resistance mutations.
* Last dose of nevirapine (NVP) or efavirenz (EFV), if applicable, ≥ 14 days prior to enrollment.

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

Primary outcomes:
measure: PK Parameter: AUCtau of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Ctau of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: AUC0-24 of TAF (Cohort 4)
timeFrame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: AUC0-24 of Bictegravir (Cohort 4)
timeFrame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Cmax of TAF (Cohort 4)
timeFrame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 24
timeFrame: Up to 24 weeks
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 24
measure: Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Change from Baseline in CD4+ Cell Counts at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in CD4+ Cell Counts at Week 48
timeFrame: Baseline, Week 48
measure: Change from Baseline in CD4+ Cell Count Percentages at Week 24
timeFrame: Baseline, Week 24
measure: Change from Baseline in CD4+ Cell Count Percentages at Week 48
timeFrame: Baseline, Week 48
measure: PK Parameter: Tmax of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Cmax of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: AUClast of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: T1/2 of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Apparent Clearance (CL) of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Apparent Vz of Bictegravir
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: AUCtau of TAF and FTC
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: AUClast of TAF and FTC (Cohorts 1, 2, and 3)
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose
measure: PK Parameter: AUClast of FTC (Cohorts 4)
timeFrame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Cmax of TAF and FTC (Cohorts 1, 2, and 3)
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose
measure: PK Parameter: Cmax of FTC (Cohorts 4)
timeFrame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Ctau of TAF and FTC
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Tmax of TAF and FTC
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: T1/2 of TAF and FTC
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Apparent CL of TAF and FTC
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: PK Parameter: Apparent Vz of TAF and FTC
timeFrame: Week 2 or Week 4 for Cohorts 1 & 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, & 24 hours postdose; Week 2 for Cohort 3: 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, & 24 hours post-dose; Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events Through Week 48
timeFrame: Up to 48 weeks
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48
timeFrame: Up to 48 weeks
measure: Acceptability of B/F/TAF Formulation at Day 1 (All Cohorts)
timeFrame: Day 1
measure: Palatability of B/F/TAF Formulation at Day 1 (All Cohorts)
timeFrame: Day 1
measure: Acceptability of B/F/TAF Formulation at Week 4 (All Cohorts)
timeFrame: Week 4
measure: Palatability of B/F/TAF Formulation at Week 4 (All Cohorts)
timeFrame: Week 4
measure: Acceptability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4)
timeFrame: Week 24
measure: Palatability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4)
timeFrame: Week 24
measure: Acceptability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)
timeFrame: Week 48
measure: Palatability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)
timeFrame: Week 48
measure: Acceptability of B/F/TAF Formulation at Week 1 (Cohort 4)
timeFrame: Week 1
measure: Palatability of B/F/TAF Formulation at Week 1 (Cohort 4)
timeFrame: Week 1
measure: Acceptability of B/F/TAF Formulation at Week 2 (Cohort 4)
timeFrame: Week 2
measure: Palatability of B/F/TAF Formulation at Week 2 (Cohort 4)
timeFrame: Week 2
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Tampa
country: United States
facility: USF Clinic at Children's Medical Services (study visits and drug storage)
state: Florida
city: Atlanta
country: United States
facility: Grady Health System Ponce Center Family and Youth Clinic
state: Georgia
city: Detroit
country: United States
facility: Wayne Pediatric Clinic
state: Michigan
city: New York
country: United States
facility: Bellevue Hospital
state: New York
city: Durham
country: United States
facility: Duke Children's Health Center, Pediatric Infectious Diseases
state: North Carolina
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children/Section of Immunology
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Bloemfontein
country: South Africa
facility: Department of Paediatrics and Child Health
city: Cape Town
country: South Africa
facility: Be Part Ypluntu Centre
city: CapeTown
country: South Africa
facility: FAMCRU, Ward J8
city: Dundee
country: South Africa
facility: Dr. J Fourie Medical Centre
city: Durban
country: South Africa
facility: Enhancing Care Foundation, Durban International Clinical Research Site
city: Johannesburg
country: South Africa
facility: Wits RHI Shandukani Research Centre, Wits Reproductive Health & HIV Institute
city: Johannesburg
country: South Africa
facility: Empilweni Service and Research Unit (ESRU)
city: Pretoria
country: South Africa
facility: VX Pharma(Pty) Ltd
city: Soweto
country: South Africa
facility: Perinatal HIV Research Unit
city: Bangkok
country: Thailand
facility: The HIV Netherlands Australia Thailand Research Collaboration
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital, Mahidol University
city: Khon Kaen
country: Thailand
facility: Faculty of Medicine, Khon Kaen University
city: Kampala
country: Uganda
facility: Makerere University, Johns Hopkins (MU-JHU) Research Collaboration
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre
city: Kampala
country: Uganda
facility: Baylor College of Medicine Children's Foundation - Uganda
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Gaur AH, Cotton MF, Rodriguez CA, McGrath EJ, Helstrom E, Liberty A, Natukunda E, Kosalaraksa P, Chokephaibulkit K, Maxwell H, Wong P, Porter D, Majeed S, Yue MS, Graham H, Martin H, Brainard DM, Pikora C. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial. Lancet Child Adolesc Health. 2021 Sep;5(9):642-651. doi: 10.1016/S2352-4642(21)00165-6. Epub 2021 Jul 22.