An Open-Label Multi-Center Study of Eculizumab in Children and Adolescents With a Diagnosis of Paroxysmal Nocturnal Hemoglobinuria
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 7
- 主要终点
- Peak And Trough Concentrations Of Eculizumab In Serum At Week 12
研究概览
简要总结
The primary objective of this study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) parameter estimates of eculizumab to confirm the dose regimens for pediatric and adolescent participants with PNH.
详细描述
This was an open-label, multi-center study of eculizumab administered to approximately 6 to 8 pediatric and adolescent participants aged 2 to 17 years with PNH. There were 3 periods in this study (screening, treatment, and post-treatment) with the treatment period having 2 dosing phases (induction and maintenance). If all screening criteria were met, the participant was eligible to enter the treatment period of the study after receiving Neisseria meningitidis (N. men), Streptococcus pneumoniae (S. pneumo), and Haemophilus influenzae (H. influ) vaccinations at least 14 days prior to first dose of study drug, or was vaccinated and received treatment with appropriate antibiotics until 14 days after the vaccinations. Participants received eculizumab intravenously (IV) based on their weight. Eculizumab was administered via an IV infusion at a rate of 5 to 10 milliliters (mL) per kilogram (kg) per hour (hr) (mL/kg/hr) for at least 25 minutes. The planned duration of treatment was 12 weeks with a 4-week induction phase and an 8-week maintenance phase. At the Investigator's and parents/legal guardian's discretion, participants who completed this study with eculizumab could continue treatment with commercially available eculizumab (Soliris®) and were followed in the Soliris® PNH Registry. Participants who stopped study participation before study completion or who did not continue with Soliris® treatment at the completion of the study were followed for 8 weeks and monitored for signs and symptoms of serious hemolysis.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants between 2 and 17 years of age;
- •Diagnosed with PNH;
- •Participants with ≥ 5% glycosylphosphatidylinositol-deficient red blood cells or granulocytes as confirmed by flow cytometry;
- •Participants must have shown evidence of hemolytic anemia as documented by lactate dehydrogenase greater than the upper limit of normal or at least 1 transfusion in the past 2 years for anemia or anemia related symptoms;
- •Written informed consent from a parent/guardian;
- •Negative pregnancy test for females of child bearing potential at screening;
- •Sexually active females must have documented a reliable and medically approved method of contraception;
- •Participant must have been vaccinated against N. men, S. pneumo, and H. influ at least 14 days prior to study drug initiation or received antibiotics for 14 days after the vaccinations.
排除标准
- •Prior eculizumab treatment;
- •Presence or suspicion of active bacterial infection at baseline;
- •Participation in another concurrent clinical study within at least 30 days prior to screening;
- •History of meningococcal/pneumococcal/gonococcal disease;
- •Pregnant, breast feeding, or intending to conceive during the study including the safety follow-up visits;
- •Any other condition that could increase the participant's risk or confound the outcome of the study.
研究组 & 干预措施
Eculizumab
Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 milligram (mg) weekly x 4; maintenance = 900 mg at Week 5; 900 mg every 2 weeks.
干预措施: Eculizumab (Drug)
结局指标
主要结局
Peak And Trough Concentrations Of Eculizumab In Serum At Week 12
时间窗: Pre-infusion and 1 hour post-infusion at End of Treatment (EOT) (Day 84 [Week 12]) or ET
Serum concentrations of eculizumab were measured by using a validated enzyme-linked immunosorbent assay (ELISA) method developed at Alexion Pharmaceuticals Bioanalytical Laboratory. The range of the analytical assay was 10 to 600 microgram per milliliter (μg/mL). Peak concentrations were not measured at the early termination (ET) visit.
次要结局
- Area Under The Curve (AUC) Of The Change From Baseline To Week 12 In Levels Of Lactate Dehydrogenase (LDH)(Baseline, EOT (Day 84 [Week 12]) or ET)
- Number Of Participants With Treatment-emergent Adverse Events (TEAEs)(First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT]))
- Concentration Of Plasma-free Hemoglobin At Baseline And Week 12(Baseline, EOT (Day 84 [Week 12]) or ET)
- Change From Baseline In LDH Levels(Baseline, Weeks 1 to 12 or ET)