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

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

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.

Study Overview

• Status: Recruiting
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: B/F/TAF (Adult Strength); Drug: B/F/TAF (Low Dose); Drug: B/F/TAF (TOS); Drug: B/F/TAF (TOS); Drug: B/F/TAF (TOS); Drug: B/F/TAF (TOS)

• Study Type: Interventional
• Enrollment (Estimated): 172
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Gilead Study Team; Email: GS-US-380-1474@gilead.com

Study Locations

• South Africa
  • Bloemfontein, South Africa, 9301
    • Completed
    • Department of Paediatrics and Child Health
  • Cape Town, South Africa, 7646
    • Recruiting
    • Be Part Ypluntu Centre
  • CapeTown, South Africa, 7505
    • Recruiting
    • FAMCRU, Ward J8
  • Dundee, South Africa, 3000
    • Active, not recruiting
    • Dr. J Fourie Medical Centre
  • Durban, South Africa, 4302
    • Recruiting
    • Enhancing Care Foundation, Durban International Clinical Research Site
  • Johannesburg, South Africa, 2092
    • Withdrawn
    • Clinical HIV Research Unit(CHRU), Wits Health Consortium, Department of Medicine, University of the Witwatersrand
  • Johannesburg, South Africa, 2112
    • Recruiting
    • Empilweni Service and Research Unit (ESRU)
  • Johannesburg, South Africa, 2038
    • Recruiting
    • Wits RHI Shandukani Research Centre, Wits Reproductive Health & HIV Institute
  • Pretoria, South Africa, 0087
    • Recruiting
    • VX Pharma(Pty) Ltd
  • Soweto, South Africa, 2013
    • Recruiting
    • Perinatal HIV Research Unit
• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Faculty of Medicine Siriraj Hospital, Mahidol University
  • Bangkok, Thailand, 10330
    • Active, not recruiting
    • The HIV Netherlands Australia Thailand Research Collaboration
  • Khon Kaen, Thailand, 40002
    • Recruiting
    • Faculty of Medicine, Khon Kaen University
• Uganda
  • Kampala, Uganda, 10005
    • Recruiting
    • Joint Clinical Research Centre
  • Kampala, Uganda
    • Recruiting
    • Baylor College of Medicine Children's Foundation - Uganda
  • Kampala, Uganda, 256
    • Recruiting
    • Makerere University, Johns Hopkins (MU-JHU) Research Collaboration
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Health System
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Completed
      • Midway Immunology and Research Center
    • Gainesville, Florida, United States, 32209
      • Completed
      • University of Florida Health
    • Tampa, Florida, United States, 33606
      • Recruiting
      • USF Clinic at Children's Medical Services (study visits and drug storage)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Completed
      • Grady Health System Ponce Center Family and Youth Clinic
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Active, not recruiting
      • Wayne Pediatric Clinic
  • New York
    • New York, New York, United States, 10016
      • Completed
      • Bellevue Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Children's Health Center, Pediatric Infectious Diseases
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • Completed
      • St. Christopher's Hospital for Children/Section of Immunology
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (12 to < 18 years of age and weight ≥ 35 kg); 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); 50/200/25 mg FDC tablets administered orally once daily without regard to food.; Other Names: Biktarvy®; GS-9883/F/TAF
Experimental: Cohort 2 (6 to < 12 years of age and weight ≥ 25 kg); 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); 50/200/25 mg FDC tablets administered orally once daily without regard to food.; Other Names: Biktarvy®; GS-9883/F/TAF
Experimental: Cohort 3 (≥ 2 years of age and weight ≥ 14 to < 25 kg); 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); 30/120/15 mg FDC tablets administered orally once daily without regard to food.; Other Names: GS-9883/F/TAF
Experimental: Open-Label Extension; 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); 50/200/25 mg FDC tablets administered orally once daily without regard to food.; Other Names: Biktarvy®; GS-9883/F/TAF; Drug: B/F/TAF (Low Dose); 30/120/15 mg FDC tablets administered orally once daily without regard to food.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 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.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 2 x B/F/TAF 3.75/15/1.88 mg (total daily dose 15/60/7.52 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 3.75/15/1.88 mg (total daily dose 7.5/30/3.76 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 1.88/7.5/0.94 mg (total daily dose 3.76/15/1.88 mg) FDC tablets administered orally as TOS, twice daily; Other Names: GS-9883/F/TAF
Experimental: Cohort 4 Group 1 (≥ 2 years of age and weight ≥ 14 to < 25 kg); 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); 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.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 2 x B/F/TAF 3.75/15/1.88 mg (total daily dose 15/60/7.52 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 3.75/15/1.88 mg (total daily dose 7.5/30/3.76 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 1.88/7.5/0.94 mg (total daily dose 3.76/15/1.88 mg) FDC tablets administered orally as TOS, twice daily; Other Names: GS-9883/F/TAF
Experimental: Cohort 4 Group 2 (≥ 1 month of age and weight ≥ 10 to < 14 kg); 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); 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.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 2 x B/F/TAF 3.75/15/1.88 mg (total daily dose 15/60/7.52 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 3.75/15/1.88 mg (total daily dose 7.5/30/3.76 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 1.88/7.5/0.94 mg (total daily dose 3.76/15/1.88 mg) FDC tablets administered orally as TOS, twice daily; Other Names: GS-9883/F/TAF
Experimental: Cohort 4 Group 3 (≥ 1 month of age and weight ≥ 6 to < 10 kg); 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); 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.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 2 x B/F/TAF 3.75/15/1.88 mg (total daily dose 15/60/7.52 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 3.75/15/1.88 mg (total daily dose 7.5/30/3.76 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 1.88/7.5/0.94 mg (total daily dose 3.76/15/1.88 mg) FDC tablets administered orally as TOS, twice daily; Other Names: GS-9883/F/TAF
Experimental: Cohort 4 Group 4 (≥ 1 month of age and weight ≥ 3 to < 6 kg); 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); 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.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 2 x B/F/TAF 3.75/15/1.88 mg (total daily dose 15/60/7.52 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 3.75/15/1.88 mg (total daily dose 7.5/30/3.76 mg) FDC tablets administered orally as TOS, twice daily.; Other Names: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 1 x B/F/TAF 1.88/7.5/0.94 mg (total daily dose 3.76/15/1.88 mg) FDC tablets administered orally as TOS, twice daily; Other Names: GS-9883/F/TAF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
PK Parameter: AUClast 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: 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
PK Parameter: Tmax of Bictegravir	Tmax is defined as the time (observed time point) of Cmax. 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: Cmax of Bictegravir	Cmax is defined as the maximum observed concentration of drug. 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: AUClast of Bictegravir	AUClast is defined as the area under the concentration of drug from time zero to the last observable concentration. 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: T1/2 of Bictegravir	T1/2 is defined as the estimate of the terminal elimination half-life of the drug. 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: Apparent Clearance (CL) of Bictegravir	CL is defined as the systemic clearance of the drug following study drug administration. 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: Apparent Vz of Bictegravir	Vz is defined as the volume of distribution of the drug after study drug administration. 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: AUCtau of TAF and FTC	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: AUClast of TAF and FTC (Cohorts 1, 2, and 3)	AUClast is defined as the area under the concentration of drug from time zero to the last observable concentration. 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.	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
PK Parameter: AUClast of FTC (Cohorts 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 and FTC (Cohorts 1, 2, and 3)	Cmax is defined as the maximum observed concentration of drug. 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.	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
PK Parameter: Cmax of FTC (Cohorts 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
PK Parameter: Ctau of TAF and FTC	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: Tmax of TAF and FTC	Tmax is defined as the time (observed time point) of Cmax. 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: T1/2 of TAF and FTC	T1/2 is defined as the estimate of the terminal elimination half-life of the drug. 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: Apparent CL of TAF and FTC	CL is defined as the systemic clearance of the drug following study drug administration. 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: Apparent Vz of TAF and FTC	Vz is defined as the volume of distribution of the drug after study drug administration. 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
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Through Week 48		Up to 48 weeks
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48		Up to 48 weeks
Acceptability of B/F/TAF Formulation at Day 1 (All Cohorts)	Participants or legal guardian will be asked: if study drug shape and size were acceptable (for Cohort 1 and Cohort 2); about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3); about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)	Day 1
Palatability of B/F/TAF Formulation at Day 1 (All Cohorts)	Participants or legal guardian will be asked about the study drug taste (All Cohorts)	Day 1
Acceptability of B/F/TAF Formulation at Week 4 (All Cohorts)	Participants or legal guardian will be asked: if study drug shape and size were acceptable (for Cohort 1 and Cohort 2); about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3).; about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)	Week 4
Palatability of B/F/TAF Formulation at Week 4 (All Cohorts)	Participants or legal guardian will be asked about the study drug taste (All Cohorts)	Week 4
Acceptability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4)	Participants or legal guardian will be asked: about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3).; about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)	Week 24
Palatability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4)	Participants or legal guardian will be asked about the study drug taste	Week 24
Acceptability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)	Participants or legal guardian will be asked: about ease of swallowability and the shape and size of study drug when swallowed (for Cohort 3).; about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste (for Cohort 4)	Week 48
Palatability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)	Participants or legal guardian will be asked about the study drug taste	Week 48
Acceptability of B/F/TAF Formulation at Week 1 (Cohort 4)	Participants or legal guardian will be asked about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste	Week 1
Palatability of B/F/TAF Formulation at Week 1 (Cohort 4)	Participants or legal guardian will be asked about the study drug taste	Week 1
Acceptability of B/F/TAF Formulation at Week 2 (Cohort 4)	Participants or legal guardian will be asked about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste	Week 2
Palatability of B/F/TAF Formulation at Week 2 (Cohort 4)	Participants or legal guardian will be asked about the study drug taste	Week 2
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
Change from Baseline in CD4+ Cell Count Percentages at Week 48		Baseline, Week 48

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2016
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 23, 2016
• First Submitted That Met QC Criteria: August 25, 2016
• First Posted (Estimated): August 26, 2016

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: GS-US-380-1474; 2016-002345-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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