Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination in Adolescents and Children With Human Immunodeficiency Virus-1
- Conditions
- HIV-1 Infection
- Interventions
- Drug: B/F/TAF (Adult Strength)Drug: B/F/TAF (Low Dose)Drug: B/F/TAF (TOS)
- Registration Number
- NCT02881320
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 177
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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1 (12 to < 18 years of age and weight ≥ 35 kg) B/F/TAF (Adult Strength) * 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. Cohort 3 (≥ 2 years of age and weight ≥ 14 to < 25 kg) B/F/TAF (Low Dose) * 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. Cohort 4 Group 3 (≥ 1 month of age and weight ≥ 6 to < 10 kg) B/F/TAF (TOS) 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. Cohort 4 Group 2 (≥ 1 month of age and weight ≥ 10 to < 14 kg) B/F/TAF (TOS) 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. Cohort 2 (6 to < 12 years of age and weight ≥ 25 kg) B/F/TAF (Adult Strength) * 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. Cohort 4 Group 1 (≥ 2 years of age and weight ≥ 14 to < 25 kg) B/F/TAF (TOS) 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. Cohort 4 Group 4 (≥ 1 month of age and weight ≥ 3 to < 6 kg) B/F/TAF (TOS) 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. Open-Label Extension B/F/TAF (Adult Strength) 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. Open-Label Extension B/F/TAF (Low Dose) 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. Open-Label Extension B/F/TAF (TOS) 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24 Up to 24 weeks PK Parameter: AUCtau of Bictegravir 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.PK Parameter: Ctau of Bictegravir 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.PK Parameter: AUC0-24 of TAF (Cohort 4) 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.PK Parameter: AUC0-24 of Bictegravir (Cohort 4) 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.PK Parameter: Cmax of TAF (Cohort 4) 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.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 24 Up to 24 weeks
- Secondary Outcome Measures
Name Time Method 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: AUClast of TAF and FTC (Cohorts 1, 2, and 3) 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.Acceptability of B/F/TAF Formulation at Week 4 (All Cohorts) 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)Palatability of B/F/TAF Formulation at Week 4 (All Cohorts) Week 4 Participants or legal guardian will be asked about the study drug taste (All Cohorts)
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 Change from Baseline in CD4+ Cell Counts at Week 48 Baseline, Week 48 PK Parameter: Apparent Clearance (CL) of Bictegravir 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.PK Parameter: Apparent Vz of Bictegravir 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.PK Parameter: Cmax of TAF and FTC (Cohorts 1, 2, and 3) 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.PK Parameter: Cmax of FTC (Cohorts 4) 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.
Change from Baseline in CD4+ Cell Counts at Week 24 Baseline, Week 24 PK Parameter: Tmax of Bictegravir 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.Change from Baseline in CD4+ Cell Count Percentages at Week 48 Baseline, Week 48 PK Parameter: AUClast of Bictegravir 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.PK Parameter: Tmax of TAF and FTC 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.PK Parameter: T1/2 of TAF and FTC 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.Change from Baseline in CD4+ Cell Count Percentages at Week 24 Baseline, Week 24 PK Parameter: Cmax of Bictegravir 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.Palatability of B/F/TAF Formulation at Day 1 (All Cohorts) Day 1 Participants or legal guardian will be asked about the study drug taste (All Cohorts)
Palatability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4) Week 48 Participants or legal guardian will be asked about the study drug taste
Palatability of B/F/TAF Formulation at Week 1 (Cohort 4) Week 1 Participants or legal guardian will be asked about the study drug taste
Palatability of B/F/TAF Formulation at Week 2 (Cohort 4) Week 2 Participants or legal guardian will be asked about the study drug taste
PK Parameter: T1/2 of Bictegravir 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.PK Parameter: AUCtau of TAF and FTC 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.PK Parameter: AUClast of FTC (Cohorts 4) 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.PK Parameter: Ctau of TAF and FTC 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.PK Parameter: Apparent Vz of TAF and FTC 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.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 Palatability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4) Week 24 Participants or legal guardian will be asked about the study drug taste
PK Parameter: Apparent CL of TAF and FTC 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.Acceptability of B/F/TAF Formulation at Day 1 (All Cohorts) 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)Acceptability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4) 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)Acceptability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4) 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)Acceptability of B/F/TAF Formulation at Week 2 (Cohort 4) 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
Acceptability of B/F/TAF Formulation at Week 1 (Cohort 4) 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
Trial Locations
- Locations (25)
Children's National Health System
🇺🇸Washington, District of Columbia, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
University of Florida Health
🇺🇸Gainesville, Florida, United States
USF Clinic at Children's Medical Services (study visits and drug storage)
🇺🇸Tampa, Florida, United States
Grady Health System Ponce Center Family and Youth Clinic
🇺🇸Atlanta, Georgia, United States
Wayne Pediatric Clinic
🇺🇸Detroit, Michigan, United States
Bellevue Hospital
🇺🇸New York, New York, United States
Duke Children's Health Center, Pediatric Infectious Diseases
🇺🇸Durham, North Carolina, United States
St. Christopher's Hospital for Children/Section of Immunology
🇺🇸Philadelphia, Pennsylvania, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Department of Paediatrics and Child Health
🇿🇦Bloemfontein, South Africa
Be Part Ypluntu Centre
🇿🇦Cape Town, South Africa
FAMCRU, Ward J8
🇿🇦CapeTown, South Africa
Dr. J Fourie Medical Centre
🇿🇦Dundee, South Africa
Enhancing Care Foundation, Durban International Clinical Research Site
🇿🇦Durban, South Africa
Wits RHI Shandukani Research Centre, Wits Reproductive Health & HIV Institute
🇿🇦Johannesburg, South Africa
Empilweni Service and Research Unit (ESRU)
🇿🇦Johannesburg, South Africa
VX Pharma(Pty) Ltd
🇿🇦Pretoria, South Africa
Perinatal HIV Research Unit
🇿🇦Soweto, South Africa
The HIV Netherlands Australia Thailand Research Collaboration
🇹🇭Bangkok, Thailand
Faculty of Medicine Siriraj Hospital, Mahidol University
🇹🇭Bangkok, Thailand
Faculty of Medicine, Khon Kaen University
🇹🇭Khon Kaen, Thailand
Makerere University, Johns Hopkins (MU-JHU) Research Collaboration
🇺🇬Kampala, Uganda
Joint Clinical Research Centre
🇺🇬Kampala, Uganda
Baylor College of Medicine Children's Foundation - Uganda
🇺🇬Kampala, Uganda