A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 129
- 试验地点
- 30
- 主要终点
- Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG) (Cohort 1)
研究概览
简要总结
The primary objectives of Cohort 1 are to evaluate the steady state pharmacokinetics (PK) for elvitegravir (EVG) and tenofovir alafenamide (TAF) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) STR (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 (Part B) in human immunodeficiency virus - 1 (HIV-1) infected, antiretroviral (ARV) treatment-naive adolescents.
The primary objectives of Cohort 2 are to evaluate the PK of EVG and TAF (Part A), and to evaluate the safety and tolerability of E/C/F/TAF through Week 24 (Part B) in virologically suppressed HIV-1 infection children 6 to < 12 years weighing >= 25 kg.
The primary objectives of Cohort 3 are to evaluate the PK of EVG and TAF and confirm the dose of the STR, and to evaluate the safety and tolerability of E/C/F/TAF low dose (LD) STR in virologically suppressed HIV-1 infected children ≥ 2 years of age and weighing ≥ 14 to < 25 kg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at baseline: 12 years to < 18 years old
- •Weight at screening: ≥ 35 kg (77 lbs)
- •Plasma HIV-1 ribonucleic acid (RNA) levels of ≥ 1,000 copies/mL at screening (Roche COBAS TaqMan v2.0)
- •Screening genotype report shows sensitivity to EVG, emtricitabine (FTC) and tenofovir (TFV)
- •No prior use of any approved or experimental anti-HIV-1 drug for any length of time
- •Age at baseline: 6 years to < 12 years old
- •Weight at screening: ≥ 25 kg (55 lbs)
- •Plasma HIV-1 RNA of < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is > 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to screening on a stable antiretroviral regimen, without documented history of resistance to any component of E/C/F/TAF STR.
- •Age at baseline: ≥ 2 years old
- •Weight at screening: ≥ 14 kg (31 lbs) to < 25 kg (55 lbs)
- •Plasma HIV-1 RNA: < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is > 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to screening on a stable antiretroviral regimen, without prior history of resistance to any component of E/C/F/TAF STR
排除标准
- •Hepatitis B or hepatitis C virus infection
- •Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit.
- •Individuals experiencing decompensated cirrhosis
- •Pregnant or lactating females
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg
Treatment naive adolescents (12 to < 18 years of age) living with human immunodeficiency virus (HIV) will receive E/C/F/TAF (150/150/200/10 mg) fixed-dose combination (FDC) once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.
干预措施: E/C/F/TAF (Drug)
Cohort 2: Age 6 to < 12 Years and Weight ≥ 25 kg
Children (6 to < 12 years of age weighing ≥ 25 kg) with HIV who were virologically suppressed will receive E/C/F/TAF (150/150/200/10 mg) FDC once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.
干预措施: E/C/F/TAF (Drug)
Cohort 3: Age ≥2 Years and Weight ≥ 14 to <25 kg
Children (≥ 2 years of age weighing ≥ 14 to < 25 kg) with HIV who were virologically suppressed will receive E/C/F/TAF (90/90/120/6 mg) FDC once daily for 48 weeks. Participants who attain a weight of ≥ 25 kg during the course of the study will switch to adult E/C/F/TAF (150/150/200/10 mg) tablets administered orally, once daily with food. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF became commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.
干预措施: E/C/F/TAF (Drug)
Cohort 3: Age ≥2 Years and Weight ≥ 14 to <25 kg
Children (≥ 2 years of age weighing ≥ 14 to < 25 kg) with HIV who were virologically suppressed will receive E/C/F/TAF (90/90/120/6 mg) FDC once daily for 48 weeks. Participants who attain a weight of ≥ 25 kg during the course of the study will switch to adult E/C/F/TAF (150/150/200/10 mg) tablets administered orally, once daily with food. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF became commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.
干预措施: E/C/F/TAF (Low Dose) (Drug)
结局指标
主要结局
Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG) (Cohort 1)
时间窗: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
PK Parameter: AUCtau of EVG (Cohort 2)
时间窗: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
PK Parameter: AUCtau of EVG (Cohort 3)
时间窗: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
PK Parameter: AUClast of Tenofovir Alafenamide (TAF) (Cohort 1)
时间窗: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4
AUClast is defined as the concentration of drug from time zero to the last observable concentration, area under the concentration time curve to last observation (AUClast).
PK Parameter: AUCtau of TAF (Cohort 3)
时间窗: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2
AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
Cohort 2: Percentage of Participants With All Treatment-Emergent AEs and Treatment-Emergent SAEs
时间窗: From first dose date up to Week 24
TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.
PK Parameter: AUClast of TAF (Cohort 2)
时间窗: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Cohort 1: Percentage of Participants With All Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
时间窗: From first dose date up to Week 24
Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.
Cohort 3: Percentage of Participants With All Treatment-Emergent AEs and Treatment-Emergent SAEs
时间窗: From first dose date up to Week 24
TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.
次要结局
- PK Parameter: Ctau of EVG, Emtricitabine (FTC), Tenofovir (TFV), and Cobicistat (COBI) (Cohort 1)(0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4)
- PK Parameter: Ctau of EVG, FTC, TFV, and COBI (Cohort 3)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2)
- PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 2)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4)
- PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 1)(0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis(Week 24)
- Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis(Week 24)
- PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 1)(0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4)
- PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 3)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2)
- PK Parameter: CL/F of EVG and TAF (Cohort 3)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2)
- PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 3)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2)
- PK Parameter: Ctau of EVG, FTC, TFV and COBI (Cohort 2)((pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4)
- PK Parameter: CL/F of EVG and TAF (Cohort 1)(0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4)
- PK Parameter: CL/F of EVG and TAF (Cohort 2)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4)
- PK Parameter: Vz/F of EVG and TAF (Cohort 3)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2)
- PK Parameter: Vz/F of EVG and TAF (Cohort 1)(0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4)
- PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 2)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis(Week 48)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis(Week 48)
- PK Parameter: Vz/F of EVG and TAF (Cohort 2)(0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis(Week 48)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis(Week 24)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses(Week 24)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Failure Analyses(Week 48)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis(Week 24)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses(Week 48)
- Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis(Week 48)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses(Week 24)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Excluded Analyses(Week 24)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Excluded Analyses(Week 48)
- Cohort 1: Change From Baseline in Cluster of Differentiation (CD4+) Cell Count at Week 24(Baseline, Week 24)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Failure Analyses(Week 24)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses(Week 24)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses(Week 48)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses(Week 48)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses(Week 24)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses(Week 48)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Failure Analyses(Week 24)
- Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Failure Analyses(Week 48)
- Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses(Week 24)
- Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses(Week 48)
- Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Week 48(Baseline, Week 48)
- Cohort 3: Change From Baseline in CD4+ Cell Percentage at Week 48(Baseline, Week 48)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Excluded Analyses(Week 24)
- Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24(Baseline, Week 24)
- Cohort 2: Change From Baseline in CD4+ Cell Count at Week 24(Baseline, Week 24)
- Cohort 3: Change From Baseline in CD4+ Cell Count at Week 24(Baseline, Week 24)
- Cohort 3: Change From Baseline in CD4+ Cell Count at Week 48(Baseline, Week 48)
- Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Excluded Analyses(Week 48)
- Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses(Week 24)
- Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses(Week 48)
- Cohort 2: Change From Baseline in CD4+ Cell Count at Week 48(Baseline, Week 48)
- Cohort 1: Change From Baseline in CD4+ Cell Percentage at Week 24(Baseline, Week 24)
- Cohort 1: Change From Baseline in CD4+ Cell Count at Week 48(Baseline, Week 48)
- Cohort 1: Change From Baseline in CD4+ Cell Percentage at Week 48(Baseline, Week 48)
- Cohort 2: Change From Baseline in CD4+ Cell Percentage at Week 24(Baseline, Week 24)
- Cohort 2: Change From Baseline in CD4+ Cell Percentage at Week 48(Baseline, Week 48)
- Cohort 3: Change From Baseline in CD4+ Cell Percentage at Week 24(Baseline, Week 24)