Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination in Adolescents and Children With Human Immunodeficiency Virus-1

NCT02881320 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: GS-US-380-14742016-002345-39
• Study Type: interventional
• Target: 177
• Locations: 4 countries
• Sites: 25

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (7)

• PK Parameter: AUCtau of Bictegravir

  AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). Cohorts 1 \& 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

  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

• PK Parameter: Ctau of Bictegravir

  Ctau is defined as the observed drug concentration at the end of the dosing interval. Cohorts 1 \& 2 Part A will participate in an Intensive PK Evaluation at Week 2 or Week 4. Samples will be collected at 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post-dose. Cohort 3 Part A will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

  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

• PK Parameter: AUC0-24 of TAF (Cohort 4)

  AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

  Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

• PK Parameter: AUC0-24 of Bictegravir (Cohort 4)

  AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

  Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

• PK Parameter: Cmax of TAF (Cohort 4)

  Cmax is defined as maximum observed concentration of drug. Cohort 4 Groups 2, 3, and 4 participants will participate in an Intensive PK evaluation at Week 2. Samples will be collected at 0 (pre-dose) 0.5, 1, 2, 4, and 8 hours post-dose.

  Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 24

  Up to 24 weeks

• Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24

  Up to 24 weeks

Secondary Outcomes (36)

• Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm

  Week 24

• Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm

  Week 48

• Change from Baseline in CD4+ Cell Counts at Week 24

  Baseline, Week 24

• Change from Baseline in CD4+ Cell Counts at Week 48

  Baseline, Week 48

• Change from Baseline in CD4+ Cell Count Percentages at Week 24

  Baseline, Week 24

Study Arms (8)

Cohort 1 (12 to < 18 years of age and weight ≥ 35 kg)

EXPERIMENTAL

* Part A: Participants will participate in an Intensive PK evaluation at Week 2 or Week 4 and continue to receive the adult strength B/F/TAF FDC through Week 48. * Part B: Following confirmation of BIC PK data from Cohort 1 Part A, participants will receive the adult strength B/F/TAF through Week 48.

Drug: B/F/TAF (Adult Strength)

Cohort 2 (6 to < 12 years of age and weight ≥ 25 kg)

EXPERIMENTAL

* Part A: Participants will participate in an Intensive PK evaluation at Week 2 or Week 4 and continue to receive the adult strength B/F/TAF FDC through Week 48. * Part B: Following confirmation of BIC PK data from Cohort 2 Part A, participants will receive the adult strength B/F/TAF FDC through Week 48.

Drug: B/F/TAF (Adult Strength)

Cohort 3 (≥ 2 years of age and weight ≥ 14 to < 25 kg)

EXPERIMENTAL

* Part A: Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive the low dose B/F/TAF FDC tablet through Week 48. * Part B: Following confirmation of BIC PK data from Cohort 3 Part A, participants will receive the low dose B/F/TAF FDC tablet through Week 48.

Drug: B/F/TAF (Low Dose)

Cohort 4 Group 1 (≥ 2 years of age and weight ≥ 14 to < 25 kg)

EXPERIMENTAL

Due to Cohort 3 Part A Intensive PK evaluation at Week 2 with the low dose B/F/TAF FDC tablet, participants will not participate in an Intensive PK evaluation at Week 2. Participants will receive B/F/TAF FDC tablets for oral suspension (TOS) once daily through Week 48.

Drug: B/F/TAF (TOS)

Cohort 4 Group 2 (≥ 1 month of age and weight ≥ 10 to < 14 kg)

EXPERIMENTAL

Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive B/F/TAF FDC TOS twice daily through Week 48.

Drug: B/F/TAF (TOS)

Cohort 4 Group 3 (≥ 1 month of age and weight ≥ 6 to < 10 kg)

EXPERIMENTAL

Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive B/F/TAF FDC TOS twice daily through Week 48.

Drug: B/F/TAF (TOS)

Cohort 4 Group 4 (≥ 1 month of age and weight ≥ 3 to < 6 kg)

EXPERIMENTAL

Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive B/F/TAF FDC TOS twice daily through Week 48.

Drug: B/F/TAF (TOS)

Open-Label Extension

EXPERIMENTAL

Following Week 48, participants in countries where B/F/TAF is not available may have the option to receive adult strength B/F/TAF FDC, low dose B/F/TAF FDC, or B/F/TAF FDC TOS (based on age and weight) until it becomes available for use according to the participant's age and weight or the product becomes accessible to participants through an access program.

Drug: B/F/TAF (Adult Strength); Drug: B/F/TAF (Low Dose); Drug: B/F/TAF (TOS)

Interventions

B/F/TAF (Adult Strength) DRUG

50/200/25 mg FDC tablets administered orally once daily without regard to food.

Also known as: Biktarvy®, GS-9883/F/TAF

Cohort 1 (12 to < 18 years of age and weight ≥ 35 kg); Cohort 2 (6 to < 12 years of age and weight ≥ 25 kg); Open-Label Extension

B/F/TAF (Low Dose) DRUG

30/120/15 mg FDC tablets administered orally once daily without regard to food.

Also known as: GS-9883/F/TAF

Cohort 3 (≥ 2 years of age and weight ≥ 14 to < 25 kg); Open-Label Extension

B/F/TAF (TOS) DRUG

2 x B/F/TAF 15/60/7.5 mg (total daily dose 30/120/15 mg) FDC tablets administered orally as TOS, once daily.

Also known as: GS-9883/F/TAF

Cohort 4 Group 1 (≥ 2 years of age and weight ≥ 14 to < 25 kg); Open-Label Extension

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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,
• mL/min/1.73 m\^2 for age \> 4 weeks to ≤ 95 days.
• mL/min/1.73 m\^2 for age ≥ 96 days to ≤ 6 months.
• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (25)

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

University of Florida Health

Gainesville, Florida, 32209, United States

Location

USF Clinic at Children's Medical Services (study visits and drug storage)

Tampa, Florida, 33606, United States

Location

Grady Health System Ponce Center Family and Youth Clinic

Atlanta, Georgia, 30322, United States

Location

Wayne Pediatric Clinic

Detroit, Michigan, 48201, United States

Location

Bellevue Hospital

New York, New York, 10016, United States

Location

Duke Children's Health Center, Pediatric Infectious Diseases

Durham, North Carolina, 27710, United States

Location

St. Christopher's Hospital for Children/Section of Immunology

Philadelphia, Pennsylvania, 19134, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Department of Paediatrics and Child Health

Bloemfontein, 9301, South Africa

Location

Be Part Ypluntu Centre

Cape Town, 7646, South Africa

Location

FAMCRU, Ward J8

CapeTown, 7505, South Africa

Location

Dr. J Fourie Medical Centre

Dundee, 3000, South Africa

Location

Enhancing Care Foundation, Durban International Clinical Research Site

Durban, 4302, South Africa

Location

Wits RHI Shandukani Research Centre, Wits Reproductive Health & HIV Institute

Johannesburg, 2038, South Africa

Location

Empilweni Service and Research Unit (ESRU)

Johannesburg, 2112, South Africa

Location

VX Pharma(Pty) Ltd

Pretoria, 0087, South Africa

Location

Perinatal HIV Research Unit

Soweto, 2013, South Africa

Location

The HIV Netherlands Australia Thailand Research Collaboration

Bangkok, 10330, Thailand

Location

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok, 10700, Thailand

Location

Faculty of Medicine, Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Makerere University, Johns Hopkins (MU-JHU) Research Collaboration

Kampala, 0000, Uganda

Location

Joint Clinical Research Centre

Kampala, 10005, Uganda

Location

Baylor College of Medicine Children's Foundation - Uganda

Kampala, Uganda

Location

Related Publications (2)

• Rodriguez CA, Natukunda E, Strehlau R, Venter EL, Rungmaitree S, Cunningham CK, Lalloo U, Kosalaraksa P, HellstrOm E, Liberty A, McGrath EJ, Kaur M, Leisegang R, Hindman JT, Vieira VA, Kersey K, Cotton MF, Rakhmanina N, Gaur AH. Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study. Lancet HIV. 2024 May;11(5):e300-e308. doi: 10.1016/S2352-3018(23)00327-2. Epub 2024 Apr 12.

  PMID: 38621393 DERIVED

• 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.

  PMID: 34302760 DERIVED

MeSH Terms

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: August 26, 2016
• Study Start: September 21, 2016
• Primary Completion: March 24, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

UG (3); ZA (9); US (10); TH (3)