AN OPEN-LABEL, MULTICENTER, MULTIPLE-DOSE PHARMACOKINETIC, SAFETY AND EFFICACY TRIAL OF MARAVIROC IN COMBINATION WITH OPTIMIZED BACKGROUND THERAPY FOR THE TREATMENT OF ANTIRETROVIRAL-EXPERIENCED CCR5-TROPIC HIV-1 INFECTED CHILDREN 2 - <18 YEARS OF AGE
试验速览
- 阶段
- 2 期
- 入组人数
- 103
- 试验地点
- 41
- 主要终点
- Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax)
研究概览
简要总结
The primary purpose of this study is to determine the pharmacokinetic properties (what the body does to maraviroc) and to determine a suitable dosing schedule of maraviroc in HIV-1 infected children and adolescents. This study will also determine whether maraviroc is safe to use in children and adolescents.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who are 2-18 years of age, treatment experienced for 6 months or longer with at least 2 ARV drug classes, with HIV-1 RNA ≥1,000 copies/mL
排除标准
- •X4- or dual/mixed-tropic virus detected by the Trofile™ viral tropism assay
- •Concomitant therapy with other investigational agents (other than experimental ARV agents available through pre-approval access programs)
- •Known ≥Grade 3 of any of the following laboratory tests at Screening or within 30 days prior to Baseline Visit: Neutrophil count, hemoglobin, platelets, AST, ALT, and creatinine, lipase;
- •Total bilirubin ≥Grade 3, unless ALL of the following are true: Current regimen includes atazanavir; ALT/AST < 2.5 X ULN; No symptoms other than jaundice or icterus.
- •Other laboratory values ≥Grade 3, must be reviewed by Pfizer.
研究组 & 干预措施
Maraviroc
Subjects will be stratified by age and formulation into one of the following cohorts:
Cohort 1: ≥2-<6 years of age, maraviroc liquid formulation; Cohort 2: ≥6-<12 years of age, maraviroc tablet formulation; Cohort 3: ≥6-<12 years of age, maraviroc liquid formulation and Cohort 4: ≥12-<18 years of age, maraviroc tablet formulation.
干预措施: Maraviroc (Drug)
结局指标
主要结局
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax)
时间窗: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
Cavg: calculated as area under the curve divided by a dosing interval of 12 hours. Cmin: directly observed plasma concentration prior to the next dose. Geometric Coefficient of Variation is defined as the geometric standard deviation to the power of the reciprocal of the geometric mean.
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality)
时间窗: Baseline up to 5 years
Incidence is reported in terms of number of events of AEs. The investigator used the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AEs as follows: Grade 1= Symptoms causing no or minimal interference with usual social and functional activities; Grade 2= Symptoms causing greater than minimal interference with usual social and functional activities; Grade 3= Symptoms causing inability to perform usual social and functional activities; Grade 4= Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data have been reported in the measure for Grade 3 and 4 as per system organ class and preferred term.
Treatment Discontinuation: Secondary Reasons- Serious Adverse Event (SAE) Related to Study Drug
时间窗: Baseline up to 5 years
The primary reason for a participant discontinuing from study drug or the clinical study was recorded in the source documents as well as the case report form. A discontinuation had to be reported immediately to the study medical monitor or his/her designated representative if it was due to an SAE and was considered as a secondary reason.
Area Under the Curve at Steady State (AUCtau)
时间窗: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
AUCtau is the area under the plasma concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 12 hours.
Time to Reach Maximum Plasma Concentration (Tmax)
时间窗: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
次要结局
- Percentage of Participants With HIV-1 RNA <400 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F) Approach(Week 24 and Week 48 post-treatment)
- Percentage of Participants With HIV-1 RNA <48 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F)Approach(Week 24 and Week 48 post-treatment)
- Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Weeks 24 and 48 Using Missing, Discontinuation = Failure (MD=F)Approach(Week 24 and Week 48 post-treatment)
- Percentage of Participants With HIV-1 RNA Levels < 48 Copies/mL at Weeks 24 and 48 Using MD=F Approach(Week 24 and Week 48 post-treatment)
- Percentage of Participants With HIV-1 RNA <400 Copies/mL and <48 Copies/mL Using the Time to Loss of Virologic Response Algorithm (TLOVR) at Week 48(Week 48)
- Percentage of Participants With >= 1.0 log10 Reduction in HIV-1RNA Concentration From Baseline to Week 24 and Week 48(Baseline to Week 24, Week 48 post-treatment)
- Change From Baseline in HIV-1 RNA (Original)(Baseline, Week 24, Week 48 post-treatment)
- Change From Baseline in HIV-1 RNA (Log10 Copies/mL)(Baseline, Week 24, Week 48 post-treatment)
- Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 24 and 48(Baseline, Week 24, Week 48 post-treatment)
- Change From Baseline in Percentage (%) of CD4+ Cells at Weeks 24 and 48(Baseline, Week 24 and Week 48 post-treatment)
- Number of Participants With Protocol Defined Virologic Failure(Week 48)
- Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48(Screening to Week 48)
- Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF(48 weeks)
- Percentage of Participants With Optimized Background Treatment Susceptibility Scores(48 weeks)