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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 177
- 试验地点
- 47
- 主要终点
- Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: B/F/TAF (Adult Strength) (Drug)
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.
干预措施: B/F/TAF (Adult Strength) (Drug)
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.
干预措施: B/F/TAF (Low Dose) (Drug)
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.
干预措施: B/F/TAF (TOS) (Drug)
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.
干预措施: B/F/TAF (TOS) (Drug)
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.
干预措施: B/F/TAF (TOS) (Drug)
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.
干预措施: B/F/TAF (TOS) (Drug)
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.
干预措施: B/F/TAF (Adult Strength) (Drug)
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.
干预措施: B/F/TAF (Low Dose) (Drug)
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.
干预措施: B/F/TAF (TOS) (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Through Week 24
时间窗: Up to 24 weeks
PK Parameter: AUCtau of Bictegravir
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: Up to 24 weeks
次要结局
- Change from Baseline in CD4+ Cell Counts at Week 48(Baseline, Week 48)
- 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)
- Acceptability of B/F/TAF Formulation at Week 4 (All Cohorts)(Week 4)
- Palatability of B/F/TAF Formulation at Week 4 (All Cohorts)(Week 4)
- 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)
- 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)
- 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)
- 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)
- PK Parameter: Cmax of FTC (Cohorts 4)(Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose)
- 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)
- 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)
- 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)
- 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)
- 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)
- Palatability of B/F/TAF Formulation at Day 1 (All Cohorts)(Day 1)
- Palatability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)(Week 48)
- Palatability of B/F/TAF Formulation at Week 1 (Cohort 4)(Week 1)
- Palatability of B/F/TAF Formulation at Week 2 (Cohort 4)(Week 2)
- 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)
- 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)
- PK Parameter: AUClast of FTC (Cohorts 4)(Week 2 for Cohort 4: 0 (predose) 0.5, 1, 2, 4, & 8 hours postdose)
- 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)
- 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)
- 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)
- 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)
- Acceptability of B/F/TAF Formulation at Day 1 (All Cohorts)(Day 1)
- Acceptability of B/F/TAF Formulation at Week 24 (Cohort 3 and Cohort 4)(Week 24)
- Acceptability of B/F/TAF Formulation at Week 48 (Cohort 3 and Cohort 4)(Week 48)
- Acceptability of B/F/TAF Formulation at Week 2 (Cohort 4)(Week 2)
- Acceptability of B/F/TAF Formulation at Week 1 (Cohort 4)(Week 1)