A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (PNH)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 9
- 主要终点
- Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose
研究概览
简要总结
The purpose of this study was to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ravulizumab in pediatric participants with paroxysmal nocturnal hemoglobinuria (PNH).
详细描述
The study consists of a 4-week Screening Period, a 26-week Primary Evaluation Period, and an Extension Period of up to 4 years (with the exception of any country-specific mandates), whichever occurs first.
Efficacy and safety data are reported for the 26-week Primary Evaluation Period only. Analyses were conducted separately for complement inhibitor treatment-naïve participants and eculizumab-experienced participants.
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
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants from birth up to <18 years of age and weighing ≥ 5 kilograms at the time of consent.
- •PNH diagnosis confirmed by documented high-sensitivity flow cytometry.
- •Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia, history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cell transfusion due to PNH.
- •Lactate dehydrogenase (LDH) level ≥ 1.5 × upper limit of normal (ULN) for participants not being treated with eculizumab at screening and LDH level ≤ 1.5 × ULN for participants taking eculizumab.
- •Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae.
- •Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
排除标准
- •History of bone marrow transplantation.
- •History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.
- •Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).
- •Females who are pregnant or breastfeeding or who have a positive pregnancy test at screening or Day
- •Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.
结局指标
主要结局
Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose
时间窗: Week 18
Blood samples for determination of ravulizumab accumulation ratio for Cmax were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Cmax from the last maintenance dose (Week 18) divided by Cmax from the first maintenance dose (Week 2).
Change In Free Complement Component C5 (C5) Concentrations Over Time
时间窗: Baseline, Weeks 2, 10, 18, and 26 (end of infusion)
Blood samples for determination of free C5 were collected before and after administration of study drug at designated time points.
Maximum Observed Serum Concentration (Cmax) Of Ravulizumab
时间窗: Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127)
Blood samples for determination of ravulizumab Cmax were collected before and after administration of study drug at designated time points. Results are reported in micrograms/milliliter (μg/mL).
Trough Serum Concentration (Ctrough) Of Ravulizumab
时间窗: Week 2 (Day 15), Week 10 (Day 71), Week 18 (Day 127), Week 26 (Day 183)
Blood samples for determination of ravulizumab Ctrough were collected before and after administration of study drug at designated time points. Trough serum concentration was measured at end of dosing interval at steady state. Results are reported in μg/mL.
Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time
时间窗: Baseline, Weeks 2, 10, 18, and 26
Blood samples for determination of cRBC hemolytic activity were collected before and after administration of study drug at designated time points.
Mean Accumulation Ratio For Ctrough Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose
时间窗: Week 18
Blood samples for determination of ravulizumab accumulation ratio for Ctrough were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Ctrough from the last maintenance dose (Week 18) divided by Ctrough from the first maintenance dose (Week 2).
次要结局
- Percentage Of Participants Who Achieved Transfusion Avoidance (TA)(Week 26)
- Percentage Of Participants With Stabilized Hemoglobin At Week 26(Week 26)
- Change In Quality Of Life (QoL) From Baseline To Week 26(Baseline, Week 26)
- Percentage Change In Free Hemoglobin From Baseline To Week 26(Baseline, Week 26)
- Percentage Change From Baseline At Week 26 In Lactate Dehydrogenase (LDH) Levels(Baseline, Week 26)
- Percentage Of Participants With Breakthrough Hemolysis (BTH) At Week 26(Week 26)