A Phase 2/3, Open-Label, Multi-Cohort Switch Study to Evaluate Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected Children and Adolescents Virologically Suppressed on a 2-NRTI-Containing Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 8
- 主要终点
- Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF)
研究概览
简要总结
The primary objective of this study is to confirm the TAF dose and to evaluate the pharmacokinetics (PK) of TAF, safety, and tolerability of F/TAF in children and adolescents with HIV-1 who are virologically suppressed (defined as having < 50 copies/mL of HIV-1 ribonucleic acid (RNA) for a period of at least 6 months) while on a stable 2 NRTI containing regimen.
详细描述
A minimum of 100 participants in total (across all cohorts) aged 1 month to <18 years of age will be enrolled to receive F/TAF. The study will proceed in sequential cohorts as follows: Cohort 1 will switch their current 2-NRTI-containing regimen to F/TAF while continuing on their 3rd ARV agent through 48 weeks; Cohorts 2, 3, and 4 must be on a boosted protease inhibitor (PI) (Cohort 2 only) or any other 3rd ARV agent and will switch their current 2-NRTI-containing regimen to F/TAF while continuing their boosted PI or 3rd ARV agent through 48 weeks. A minimum of 10 participants each in Groups 1 and 2 of Cohort 2, and Cohorts 3 and 4, who are on boosted-ATV as their 3rd ARV agent will be enrolled. Cohorts 2, 3, and 4 will be enrolled by cohort into a two-part study (Parts A and B).
After completion of 48 weeks, all participants will be given the option to participate in an extension phase of the study. Gilead will provide F/TAF until a) The participant turns 18 years old and F/TAF is commercially available for use in adults in the country in which the participant is enrolled or b), F/TAF becomes commercially available for pediatric use in the country in which the participant is enrolled or c), Gilead Sciences elects to terminate development of F/TAF in the applicable country.
However, Cohort 2 (Part B), Cohorts 3 and 4 were not conducted as planned.
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
- •Human immunodeficiency virus 1 (HIV-1) infected male and female adolescents and children aged 1 month to < 18 years at baseline/Day 1 (according to requirements of the enrolling cohort)
- •Must be able to give written assent prior to any screening evaluations
- •Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
- •Body weight at screening as follows:
- •Cohort 1: ≥ 35 kg
- •Cohort 2, Group 1: ≥ 25 kg
- •Cohort 2, Group 2: 17 kg to < 25 kg
- •Cohort 3: to be updated per a protocol amendment
- •Cohort 4: to be updated per a protocol amendment
- •Currently on a stable 2-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) containing regimen that includes a 3rd antiretroviral (ARV) agent for ≥ 6 consecutive months prior to screening
- •Plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL for ≥ 6 consecutive months preceding the screening visit
- •No opportunistic infection within 30 days of study entry (at baseline/Day 1)
- •A negative serum β-human chorionic gonadotropin (HCG) pregnancy test is required for females of childbearing potential only
排除标准
- •An acquired immunodeficiency syndrome (AIDS) - indicator condition with onset within 30 days prior to screening
- •Life expectancy of < 2 years
- •Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline/Day 1
- •Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit
- •Active hepatitis C virus (HCV) infection defined as positive for HCV antibody and having detectable HCV RNA
- •Positive hepatitis B surface antigen or other evidence of active hepatitis B virus (HBV) infection.
- •Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment, or compliance with the protocol.
- •Pregnant or lactating females
- •Have history of significant drug sensitivity or drug allergy
- •Have previously participated in an investigational trial involving administration of any investigational agent, other than TDF, within 30 days prior to the study dosing
- •NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
FTC/TAF+3rd ARV Agent (Cohort 3, Part A)
Participants between 2 to < 6 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
干预措施: 3rd ARV agent (Drug)
FTC/TAF+3rd ARV Agent (Cohort 4, Part A)
Participants between 1 month to < 2 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
干预措施: F/TAF (Drug)
F/TAF+3rd ARV Agent (Cohort 1)
Participants between 12 to < 18 years of age and ≥ 35 kg in body weight will switch their current 2-NRTI containing regimen to F/TAF (200/25 mg for unboosted 3rd agent and 200/10 mg for boosted 3rd agent) while continuing on their 3rd ARV agent for 48 weeks.
干预措施: F/TAF (Drug)
F/TAF+3rd ARV Agent (Cohort 1)
Participants between 12 to < 18 years of age and ≥ 35 kg in body weight will switch their current 2-NRTI containing regimen to F/TAF (200/25 mg for unboosted 3rd agent and 200/10 mg for boosted 3rd agent) while continuing on their 3rd ARV agent for 48 weeks.
干预措施: 3rd ARV agent (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 1)
Participants between 6 to < 12 years of age and ≥ 25 kg in body weight must be on a boosted protease inhibitor (PI) as their 3rd ARV agent and will switch their current 2-NRTI regimen to F/TAF 200/25 mg while continuing on their boosted PI for 48 weeks.
干预措施: F/TAF (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 1)
Participants between 6 to < 12 years of age and ≥ 25 kg in body weight must be on a boosted protease inhibitor (PI) as their 3rd ARV agent and will switch their current 2-NRTI regimen to F/TAF 200/25 mg while continuing on their boosted PI for 48 weeks.
干预措施: Boosted PIs (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2)
Participants between 2 to < 12 years of age and between 17 kg to < 25 kg in body weight must be on a boosted protocol specified 3rd ARV agent and will switch their current 2-NRTI containing regimen to F/TAF 120/15 mg while continuing their 3rd ARV agent for 48 weeks.
干预措施: F/TAF (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2)
Participants between 2 to < 12 years of age and between 17 kg to < 25 kg in body weight must be on a boosted protocol specified 3rd ARV agent and will switch their current 2-NRTI containing regimen to F/TAF 120/15 mg while continuing their 3rd ARV agent for 48 weeks.
干预措施: 3rd ARV agent (Drug)
FTC/TAF+3rd ARV Agent (Cohort 3, Part A)
Participants between 2 to < 6 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
干预措施: F/TAF (Drug)
FTC/TAF+3rd ARV Agent (Cohort 4, Part A)
Participants between 1 month to < 2 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
干预措施: 3rd ARV agent (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 1)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: F/TAF (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 1)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: 3rd ARV agent (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 2)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: F/TAF (Drug)
F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 2)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: 3rd ARV agent (Drug)
FTC/TAF+3rd ARV Agent (Cohort 3, Part B)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: F/TAF (Drug)
FTC/TAF+3rd ARV Agent (Cohort 3, Part B)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: 3rd ARV agent (Drug)
FTC/TAF+3rd ARV Agent (Cohort 4, Part B)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: F/TAF (Drug)
FTC/TAF+3rd ARV Agent (Cohort 4, Part B)
Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.
干预措施: 3rd ARV agent (Drug)
FTC/TAF+3rd ARV Agent (Extension Phase)
After completion of 48 weeks, all participants will be given the option to participate in an extension phase of the study. Gilead will provide F/TAF until a) the participant turns 18 and F/TAF is commercially available for use in adults in the country in which the participant is enrolled or, b) F/TAF becomes commercially available for pediatric use in the country in which the participant is enrolled or, c) Gilead Sciences elects to terminate development of F/TAF in the applicable country.
干预措施: F/TAF (Drug)
FTC/TAF+3rd ARV Agent (Extension Phase)
After completion of 48 weeks, all participants will be given the option to participate in an extension phase of the study. Gilead will provide F/TAF until a) the participant turns 18 and F/TAF is commercially available for use in adults in the country in which the participant is enrolled or, b) F/TAF becomes commercially available for pediatric use in the country in which the participant is enrolled or, c) Gilead Sciences elects to terminate development of F/TAF in the applicable country.
干预措施: 3rd ARV agent (Drug)
结局指标
主要结局
Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF)
时间窗: Any time at Week 2 visit
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of TAF
时间窗: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24
时间窗: Baseline through Week 24
An AE is any untoward medical occurrence in a clinical study participant which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The TEAEs were defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.
次要结局
- PK Parameter (Cohort 1): Clast of TAF(Any time at Week 2 visit)
- PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV(Any time at Week 2 visit)
- PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV(Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits)
- PK Parameter (Cohort 2: Part A - Groups 1 and 2): Clast of TAF(Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits)
- PK Parameter (Cohort 1): CL/F of TAF(Any time at Week 2 visit)
- PK Parameter (Cohort 2: Part A - Groups 1 and 2): CL/F of TAF(Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits)
- PK Parameter (Cohort 1): Vz/F of TAF(Any time at Week 2 visit)
- PK Parameter (Cohort 2: Part A - Groups 1 and 2): Vz/F of TAF(Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits)
- PK Parameter (Cohort 1): AUCtau of FTC and TFV(Any time at Week 2 visit)
- PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV(Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits)
- PK Parameter (Cohort 1): Ctau of FTC and TFV(Any time at Week 2 visit)
- PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV(Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits)
- Percentage of Participants Experiencing TEAEs and SAEs Through Week 48(Baseline through Week 48)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm(Week 24)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the US FDA-Defined Snapshot Algorithm(Week 48)
- Change From Baseline in CD4+ Cell Count at Week 24(Baseline, Week 24)
- Change From Baseline in CD4+ Cell Count at Week 48(Baseline, Week 48)
- Change From Baseline in CD4 Percentage at Week 24(Baseline, Week 24)
- Change From Baseline in CD4 Percentage at Week 48(Baseline, Week 48)
- Number of Participants With Palatability of F/TAF Formulation(Week 2 (for Cohort 1), Week 2 and Week 4 (for Cohort 2))
- Number of Participants With Acceptability of F/TAF Formulation(Baseline up to Week 4)