A Phase 3, Open-Label, Multicenter Study of ALXN1210 in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 19
- 主要终点
- Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
研究概览
简要总结
The purpose of the study is to assess the efficacy of ravulizumab to control disease activity in children and adolescents with aHUS who have not previously used a complement inhibitor (complement inhibitor treatment-naïve), as well as in complement inhibitor-experienced (eculizumab-experienced) adolescent participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Complement Inhibitor Treatment Naïve:
- •Participants from birth up to <18 years of age and weighing ≥5 kilograms (kg) at the time of consent.
- •Participants had not been previously treated with complement inhibitors.
- •Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
- •Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
- •Female participants of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
- •Eculizumab Experienced:
- •Participants between 12 and <18 years of age (non-Japanese sites) or <18 years of age (Japanese sites) who had been treated with eculizumab according to the labelled dosing recommendation for aHUS for at least 90 days prior to screening.
- •Participants with documented diagnosis of aHUS.
- •Participants with clinical evidence of response to eculizumab indicated by stable TMA parameters at screening.
- •Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.
- •Females of childbearing potential and male participants with female partners of childbearing potential must have used highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
排除标准
- •Known familial or acquired ADAMTS13 ("a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13") deficiency (activity <5%).
- •Known Shiga toxin-related hemolytic uremic syndrome.
- •Positive direct Coombs test.
- •Females who planned to become pregnant during the study or were currently pregnancy or breastfeeding.
- •Identified drug exposure-related hemolytic uremic syndrome.
- •Bone marrow transplant/hematopoietic stem cell transplant within the last 6 months prior to the start of screening.
- •Hemolytic uremic syndrome related to known genetic defects of cobalamin C metabolism.
- •Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
- •Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease.
- •For eculizumab-experienced participants, prior use of complement inhibitors other than eculizumab.
- •For eculizumab-experienced participants, any known abnormal TMA parameters within 90 days prior to screening.
结局指标
主要结局
Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26
时间窗: Week 26
Complete TMA response during the 26-week Initial Evaluation Period is a composite outcome measure that required normalization of hematological parameters (platelet count and lactate dehydrogenase \[LDH\]) and improvement in kidney function (≥25% reduction in serum creatinine from baseline); for participants on dialysis, baseline was established at least 6 days after the end of dialysis. Participants had to meet these criteria for 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment. Formal statistical comparison analyses were not planned for this study. Percentage based on the responders among treated participants. Confidence interval (CI) based on exact confidence limits using the Clopper Pearson method.
次要结局
- Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants(Baseline through at least Week 52 and up to Week 111)
- Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire (Participants ≥5 Years Of Age) At Weeks 26 and 52(Baseline, Week 26 and Week 52)
- Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52(Week 52)
- Change From Baseline In LDH At Weeks 26 and 52(Baseline, Week 26 and Week 52)
- Change From Baseline In Platelet Count At Weeks 26 and 52(Baseline, Week 26 and Week 52)
- Participants Who Do Not Require Dialysis at Weeks 26 and 52(Week 26 and Week 52)
- Participants With Change From Baseline In CKD Stage At Weeks 26 and 52(Baseline, Week 26, and Week 52)
- Change From Baseline In Hemoglobin At Weeks 26 and 52(Baseline, Week 26 and Week 52)
- Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin ≥20 g/L Through Week 26 and Week 52(Baseline through Week 26 and through Week 52)
- Change From Baseline In eGFR At Weeks 26 and 52(Baseline, Week 26 and Week 52)