A Phase II, Open Label, Single Arm Trial to Evaluate the Pharmacokinetics,Safety, Tolerability, and Antiviral Activity of Rilpivirine (TMC278) in Antiretroviral Naive HIV-1 Infected Adolescents and Children Aged >= 6 to <18 Years
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 主要终点
- Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
研究概览
简要总结
The purpose of this study is to evaluate the pharmacokinetics, safety and antiviral activity of rilpivirine (TMC278) 25 milligram (mg) or adjusted dose once daily in combination with an investigator-selected background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTIs) (zidovudine [AZT], abacavir [ABC], or tenofovir disoproxil fumarate [TDF] in combination with lamivudine [3TC] or emtricitabine [FTC] in antiretroviral (ARV) treatment-naïve adolescents and children aged greater than or equal to (>=) 6 to less than (<) 18 years.
详细描述
This is a Phase II, open-label (all people involved know the identity of the assigned drug) and single arm study. The study will consist of a screening period of maximum 8 weeks, an initial treatment period of 48 weeks, a post week 48 treatment extension period of 4 years (Cohort 1 only), and a 4 week follow-up (cohort 2 only) period. Participants who withdraw from the trial on or before the Week 48 visit or subjects with ongoing (serious) adverse events ([S]AEs), laboratory abnormalities, or viral load increase at the last on-treatment visit in the extension, will be seen for a follow-up visit 4 weeks later. The initial 48-week treatment period will be structured into 2 age Cohorts; Cohort 1 (Aged greater than or equal to [>=] 12 to less than [<] 18 years) and Cohort 2 (Children Aged >= 6 to < 12 years). The trial is designed to evaluate the steady-state pharmacokinetic (PK) profile (based on intensive PK analysis) and the short-term safety and antiviral activity of rilpivirine (RPV). Participants will receive RPV 25 milligram (mg), or weight-adjusted dose orally once daily for 240 weeks when administered in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). The trial will also evaluate long-term (48 weeks and 240 weeks [Cohort 1]) safety, efficacy, and pharmacokinetics of rilpivirine in combination with the background regimen of 2 NRTIs. Patients safety will be monitored throughout the study and during the follow up visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has documented human immuno deficiency virus (HIV-1) infection
- •Patients who meet the following criteria; a) Cohort 1: Patients Aged greater than or equal to (>=) 12 to less than (<) 18 years, weight is >= 32 kilogram (kg), b) Cohort 2; Aged >= 6 to < 12 years, weight is >= 17 kg
- •Must have HIV-1 plasma viral load at screening greater than equal to 500 HIV-1 ribonucleic acid (RNA) copies/mL
- •Have not received treatment with a therapeutic HIV vaccine or an HIV drug with the exception of a single dose of nevirapine (NVP) (Cohort 1 and Cohort 2) or up to 6 weeks of zidovudine (AZT) use (Cohort 2 only) prior to screening to prevent mother-to-child transmission (MTCT)
- •In the judgment of the investigator, it is appropriate to initiate antiretroviral therapy (ARV) therapy based on a patient's medical condition and taking into account guidelines for the treatment of HIV-1 infection in children of this age group
排除标准
- •Any previous use of ARVs with the exception of single dose NVP (Cohort 1 and Cohort 2) or up to 6 weeks of AZT (Cohort 2 only) to prevent MTCT
- •Plasma viral load at screening greater than 100,000 HIV-1 RNA copies/mL
- •Documented genotypic evidence of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance at screening or from historical data available in the source documents
- •Use of disallowed concomitant therapy from 4 weeks prior to the baseline visit
- •Patient has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness
- •Patient has active tuberculosis and/or is being treated for tuberculosis at screening
- •Personal history of cardiac disease (including congenital heart disease), or symptomatic arrhythmias, with the exception of sinus arrhythmia; personal history of asymptomatic arrhythmias is excluded if the asymptomatic arrhythmia is clinically significant in the opinion of the investigator
研究组 & 干预措施
Rilpivirine (TMC278)
The patients received rilpivirine with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a background regimen in cohort 1 [aged greater than or equal to (> =) 12 to less than (<) 18 years] for up to 240 weeks which is already completed and recruitment closed and will receive this treatment in cohort 2 (children aged > = 6 to < 12 years) for up to 48 weeks. The NRTIs include zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.
干预措施: Rilpivirine (Drug)
Rilpivirine (TMC278)
The patients received rilpivirine with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a background regimen in cohort 1 [aged greater than or equal to (> =) 12 to less than (<) 18 years] for up to 240 weeks which is already completed and recruitment closed and will receive this treatment in cohort 2 (children aged > = 6 to < 12 years) for up to 48 weeks. The NRTIs include zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.
干预措施: Zidovudine (Drug)
Rilpivirine (TMC278)
The patients received rilpivirine with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a background regimen in cohort 1 [aged greater than or equal to (> =) 12 to less than (<) 18 years] for up to 240 weeks which is already completed and recruitment closed and will receive this treatment in cohort 2 (children aged > = 6 to < 12 years) for up to 48 weeks. The NRTIs include zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.
干预措施: Abacavir (Drug)
Rilpivirine (TMC278)
The patients received rilpivirine with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a background regimen in cohort 1 [aged greater than or equal to (> =) 12 to less than (<) 18 years] for up to 240 weeks which is already completed and recruitment closed and will receive this treatment in cohort 2 (children aged > = 6 to < 12 years) for up to 48 weeks. The NRTIs include zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.
干预措施: Tenofovir disoproxil fumarate (Drug)
Rilpivirine (TMC278)
The patients received rilpivirine with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a background regimen in cohort 1 [aged greater than or equal to (> =) 12 to less than (<) 18 years] for up to 240 weeks which is already completed and recruitment closed and will receive this treatment in cohort 2 (children aged > = 6 to < 12 years) for up to 48 weeks. The NRTIs include zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.
干预措施: Lamivudine (Drug)
Rilpivirine (TMC278)
The patients received rilpivirine with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) as a background regimen in cohort 1 [aged greater than or equal to (> =) 12 to less than (<) 18 years] for up to 240 weeks which is already completed and recruitment closed and will receive this treatment in cohort 2 (children aged > = 6 to < 12 years) for up to 48 weeks. The NRTIs include zidovudine, abacavir, or tenofovir disoproxil fumarate in combination with lamivudine or emtricitabine.
干预措施: Emtricitabine (Drug)
结局指标
主要结局
Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
时间窗: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
Cmax,ss was the maximum observed plasma concentration of rilpivirine at steady state (steady state starting from Day 14).
Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss)
时间窗: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
Cmax,ss was the maximum plasma concentration of rilpivirine at steady state (steady state starting from Day 14). In the below data table, the measure type "Number" corresponds to Cmax,ss concentration.
Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)
时间窗: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
AUC24,ss was defined as the area under the plasma concentration versus time curve from time 0 to 24 hours post dosing of rilpivirine at steady state (steady state starting from Day 14).
Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)
时间窗: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
AUC24,ss was defined as the area under the plasma concentration versus time curve from time 0 to 24 hours post dosing of rilpivirine at steady state (steady state starting from Day 14). In the below data table, the measure type "Number" corresponds to AUC24, ss concentration.
次要结局
- Cohorts 1 and 2: Number of Participants With Adverse Events (AEs)(Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From Baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10))
- Cohorts 1 and 2: Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) Level Less Than (<) 50 Copies/mL by Time to Loss of Virologic Response (TLOVR) Method(At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only))
- Cohorts 1 and 2: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL by Food and Drug Administration (FDA) Snapshot Approach(At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only))
- Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data(Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10))
- Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability(Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10))
- Cohorts 1 and 2: Change From Baseline in Cluster of Differentiation (CD4+) Cells(Baseline (Day 1) and Week 48 for Cohorts 1 and 2; Week 240 for Cohort 1 alone)