B/F/TAF FDC in HIV-1 Infected Adolescents and Children

• ClinicalTrials.gov Identifier: NCT02881320
• Recruitment Status: Recruiting
• First Posted: August 26, 2016
• Last Update Posted: February 1, 2023
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

Cohort 1 and 2:

The primary objectives of this study are:

Part A:

• To evaluate the steady state pharmacokinetics (PK) of bictegravir (BIC) and confirm the dose of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed adolescents (12 to < 18 years of age) and children (6 to < 12 years of age)

Parts A and B:

• To evaluate the safety and tolerability of the adult strength B/F/TAF FDC through Week 24 in HIV-1 infected, virologically suppressed adolescents (12 to <18 years of age) and children (6 to <12 years of age)

Cohort 3:

The primary objectives of this study are:

Part A:

• To evaluate the steady state PK of BIC and confirm the dose of B/F/TAF 30/120/15 mg FDC in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg

Parts A and B:

• To evaluate the safety and tolerability of the low dose B/F/TAF FDC tablet through Week 24 in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg

Cohort 4:

Group 1:

The primary objective of this study is:

• To evaluate the safety and tolerability of B/F/TAF 30/120/15 mg (administration of 2 x B/F/TAF 15/60/7.5 mg FDC tablets for oral suspension (TOS)) once daily through Week 24 in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg who are unable to swallow tablets

Group 2:

The primary objectives of this study are:

• To evaluate the steady state PK of BIC and TAF and confirm the dose of B/F/TAF 7.5/30/3.75 mg (administration of 2 × B/F/TAF 3.75/15/1.88 mg FDC TOS) twice daily in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 10 to < 14 kg
• To evaluate the safety and tolerability of B/F/TAF 7.5/30/3.75 mg (administration of 2 × B/F/TAF 3.75/15/1.88 mg FDC TOS) twice daily through Week 24 in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 10 to < 14 kg

Group 3:

The primary objectives of this study are:

• To evaluate the steady state PK of BIC and TAF and confirm the dose of B/F/TAF 3.75/15/1.88 mg (administration of 1 × B/F/TAF 3.75/15/1.88 mg FDC TOS) twice daily in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 6 to < 10 kg
• To evaluate the safety and tolerability of B/F/TAF 3.75/15/1.88 mg (administration of 1 × B/F/TAF 3.75/15/1.88 mg FDC TOS) twice daily through Week 24 in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 6 to < 10 kg

Group 4:

The primary objectives of this study are:

• To evaluate the steady state PK of BIC and TAF and confirm the dose of B/F/TAF 1.88/7.5/0.94 mg (administration of 1 × B/F/TAF 1.88/7.5/0.94 mg FDC TOS) twice daily in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 3 to < 6 kg
• To evaluate the safety and tolerability of B/F/TAF 1.88/7.5/0.94 mg (administration of 1 × B/F/TAF 1.88/7.5/0.94 mg FDC TOS) twice daily through Week 24 in HIV-1 infected children ≥ 1 month of age, on ARV treatment or treatment naive, weighing ≥ 3 to < 6 kg

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: B/F/TAF (Adult Strength); Drug: B/F/TAF (Low Dose); Drug: B/F/TAF (TOS)	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 172 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 21, 2016
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

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: GS-9883/F/TAF; Biktarvy®
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: GS-9883/F/TAF; Biktarvy®
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 Name: 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 FDC of bictegravir 15 mg/emtricitabine 60 mg/ tenofovir alafenamide 7.5 mg (B/F/TAF 15/60/7.5 mg) (total dose 30/120/15 mg) administered orally as TOS, once daily without regard to food; Other Name: 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); FDC of bictegravir 15 mg/emtricitabine 60 mg/ tenofovir alafenamide 7.5 mg (B/F/TAF 15/60/7.5 mg) administered orally as TOS, once daily without regard to food; Other Name: 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 FDC of bictegravir 3.75 mg/emtricitabine 15 mg/ tenofovir alafenamide 1.88 mg (B/F/TAF 3.75/15/1.88 mg) (total dose 7.5/30/3.75 mg) administered orally as TOS, once daily without regard to food; Other Name: 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); FDC of bictegravir 3.75 mg/emtricitabine 15 mg/ tenofovir alafenamide 1.88 mg (B/F/TAF 3.75/15/1.88 mg) administered orally as TOS, once daily without regard to food; Other Name: 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: GS-9883/F/TAF; Biktarvy®; Drug: B/F/TAF (Low Dose); 30/120/15 mg FDC tablets administered orally once daily without regard to food; Other Name: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 2 x FDC of bictegravir 15 mg/emtricitabine 60 mg/ tenofovir alafenamide 7.5 mg (B/F/TAF 15/60/7.5 mg) (total dose 30/120/15 mg) administered orally as TOS, once daily without regard to food; Other Name: GS-9883/F/TAF; Drug: B/F/TAF (TOS); FDC of bictegravir 15 mg/emtricitabine 60 mg/ tenofovir alafenamide 7.5 mg (B/F/TAF 15/60/7.5 mg) administered orally as TOS, once daily without regard to food; Other Name: GS-9883/F/TAF; Drug: B/F/TAF (TOS); 2 x FDC of bictegravir 3.75 mg/emtricitabine 15 mg/ tenofovir alafenamide 1.88 mg (B/F/TAF 3.75/15/1.88 mg) (total dose 7.5/30/3.75 mg) administered orally as TOS, once daily without regard to food; Other Name: GS-9883/F/TAF; Drug: B/F/TAF (TOS); FDC of bictegravir 3.75 mg/emtricitabine 15 mg/ tenofovir alafenamide 1.88 mg (B/F/TAF 3.75/15/1.88 mg) administered orally as TOS, once daily without regard to food; Other Name: GS-9883/F/TAF

Outcome Measures

Primary Outcome Measures :

1. PK Parameter: AUCtau of Bictegravir [ Time Frame: 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 ]

   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.

2. PK Parameter: Ctau of Bictegravir [ Time Frame: 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 ]

   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.

3. PK Parameter: AUClast of TAF (Cohort 4) [ Time Frame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose ]

   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.

4. PK Parameter: Cmax of TAF (Cohort 4) [ Time Frame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose ]
   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.
5. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 24 [ Time Frame: Up to 24 weeks ]
6. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24 [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :

1. Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm [ Time Frame: Week 24 ]
2. Proportion of Participants with Plasma HIV-1 RNA < 50 copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm [ Time Frame: Week 48 ]
3. Change from Baseline in CD4+ Cell Counts at Week 24 [ Time Frame: Baseline, Week 24 ]
4. Change from Baseline in CD4+ Cell Counts at Week 48 [ Time Frame: Baseline, Week 48 ]
5. Change from Baseline in CD4+ Cell Count Percentages at Week 24 [ Time Frame: Baseline, Week 24 ]
6. Change from Baseline in CD4+ Cell Count Percentages at Week 48 [ Time Frame: Baseline, Week 48 ]
7. PK Parameter: Tmax of Bictegravir [ Time Frame: 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 ]

   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.

8. PK Parameter: Cmax of Bictegravir [ Time Frame: 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 ]

   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.

9. PK Parameter: AUClast of Bictegravir [ Time Frame: 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 ]

   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.

10. PK Parameter: T1/2 of Bictegravir [ Time Frame: 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 ]

    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.

11. PK Parameter: Apparent Clearance (CL) of Bictegravir [ Time Frame: 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 ]

    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.

12. PK Parameter: Apparent Vz of Bictegravir [ Time Frame: 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 ]

    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.

13. PK Parameter: AUCtau of TAF and FTC [ Time Frame: 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 ]

    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.

14. PK Parameter: AUClast of TAF and FTC (Cohorts 1, 2, and 3) [ Time Frame: 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 ]

    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.

15. PK Parameter: AUClast of FTC (Cohorts 4) [ Time Frame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose ]

    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.

16. PK Parameter: Cmax of TAF and FTC (Cohorts 1, 2, and 3) [ Time Frame: 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 ]

    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.

17. PK Parameter: Cmax of FTC (Cohorts 4) [ Time Frame: Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose ]
    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.
18. PK Parameter: Ctau of TAF and FTC [ Time Frame: 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 ]

    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.

19. PK Parameter: Tmax of TAF and FTC [ Time Frame: 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 ]

    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.

20. PK Parameter: T1/2 of TAF and FTC [ Time Frame: 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 ]

    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.

21. PK Parameter: Apparent CL of TAF and FTC [ Time Frame: 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 ]

    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.

22. PK Parameter: Apparent Vz of TAF and FTC [ Time Frame: 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 ]

    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.

23. Percentage of Participants Experiencing Treatment-Emergent Adverse Events Through Week 48 [ Time Frame: Up to 48 weeks ]
24. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 48 [ Time Frame: Up to 48 weeks ]
25. Acceptability of B/F/TAF Formulation at Day 1 (All Cohorts) [ Time Frame: Day 1 ]

    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)
26. Palatability of B/F/TAF Formulation at Day 1 (All Cohorts) [ Time Frame: Day 1 ]
    Participants or legal guardian will be asked about the study drug taste (All Cohorts)
27. Acceptability of B/F/TAF Formulation at Week 4 (All Cohorts) [ Time Frame: Week 4 ]

    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)
28. Palatability of B/F/TAF Formulation at Week 4 (All Cohorts) [ Time Frame: Week 4 ]
    Participants or legal guardian will be asked about the study drug taste (All Cohorts)
29. Acceptability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4) [ Time Frame: Week 24 ]

    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)
30. Palatability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4) [ Time Frame: Week 24 ]
    Participants or legal guardian will be asked about the study drug taste
31. Acceptability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4) [ Time Frame: Week 48 ]

    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)
32. Palatability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4) [ Time Frame: Week 48 ]
    Participants or legal guardian will be asked about the study drug taste
33. Acceptability of B/F/TAF Formulation at Week 1 (Cohort 4) [ Time Frame: Week 1 ]
    Participants or legal guardian will be asked about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste
34. Palatability of B/F/TAF Formulation at Week 1 (Cohort 4) [ Time Frame: Week 1 ]
    Participants or legal guardian will be asked about the study drug taste
35. Acceptability of B/F/TAF Formulation at Week 2 (Cohort 4) [ Time Frame: Week 2 ]
    Participants or legal guardian will be asked about their understanding of instructions, preparation of the study drug formulation and study drug administration and taste
36. Palatability of B/F/TAF Formulation at Week 2 (Cohort 4) [ Time Frame: Week 2 ]
    Participants or legal guardian will be asked about the study drug taste

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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 (GFR) ≥ 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 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 > 2 months 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.

Contacts and Locations

Contacts

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

Locations

United States, District of Columbia

Children's National Health System; Recruiting

Washington, District of Columbia, United States, 20010

United States, Florida

Midway Immunology and Research Center; Completed

Fort Pierce, Florida, United States, 34982

University of Florida Health; Completed

Gainesville, Florida, United States, 32209

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

Tampa, Florida, United States, 33606

United States, Georgia

Grady Health System Ponce Center Family and Youth Clinic; Completed

Atlanta, Georgia, United States, 30322

United States, Michigan

Wayne Pediatric Clinic; Recruiting

Detroit, Michigan, United States, 48201

United States, New York

Bellevue Hospital; Completed

New York, New York, United States, 10016

United States, North Carolina

Duke Children's Health Center, Pediatric Infectious Diseases; Recruiting

Durham, North Carolina, United States, 27710

United States, Pennsylvania

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

Philadelphia, Pennsylvania, United States, 19134

United States, Tennessee

St. Jude Children's Research Hospital; Recruiting

Memphis, Tennessee, United States, 38105

South Africa

Empilweni Service and Research Unit (ESRU); Recruiting

Johannesburg, Gauteng, South Africa, 2112

Dr. J Fourie Medical Centre; Active, not recruiting

Dundee, KwaZulu-Natal, South Africa, 3000

Be Part Ypluntu Centre; Recruiting

Cape Town, Western Cape, South Africa, 7646

Department of Paediatrics and Child Health; Active, not recruiting

Bloemfontein, South Africa, 9301

KIDCRUM Tygerberg Children's Hospital; Recruiting

Cape Town, South Africa, 7505

Enhancing Care Foundation, Durban International Clinical Research Site; Recruiting

Durban, South Africa, 4302

Clinical HIV Research Unit(CHRU), Wits Health Consortium, Department of Medicine, University of the Witwatersrand; Withdrawn

Johannesburg, South Africa, 2092

VX Pharma(Pty) Ltd; Recruiting

Pretoria, South Africa, 0087

Perinatal HIV Research Unit; Recruiting

Soweto, South Africa, 2013

Thailand

The HIV Netherlands Australia Thailand Research Collaboration; Active, not recruiting

Bangkok, Thailand, 10330

Faculty of Medicine Siriraj Hospital, Mahidol University; Active, not recruiting

Bangkok, Thailand, 10700

Faculty of Medicine, Khon Kaen University; Active, not recruiting

Khon Kaen, Thailand, 40002

Uganda

Joint Clinical Research Centre; Recruiting

Kampala, Uganda, 10005

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02881320
• Other Study ID Numbers: GS-US-380-1474; 2016-002345-39 ( EudraCT Number )
• First Posted: August 26, 2016
• Last Update Posted: February 1, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No