Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-naïve Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 37
- 主要终点
- Percentage Of 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 safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor.
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
- •Male or female ≥ 12 years of age and weighing ≥ 40 kg at the time of consent.
- •Evidence of thrombotic microangiopathy, 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, or at the time of, initiating study drug. Participants who received a meningococcal vaccine less than 2 weeks before initiating ravulizumab treatment must have received treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Participants who had not been vaccinated prior to initiating ravulizumab treatment should have received prophylactic antibiotics prior to and for at least 2 weeks after meningococcal vaccination. Participants < 18 years of age must have been vaccinated against haemophilus influenzae type b and streptococcus pneumoniae according to national and local vaccination schedule guidelines.
- •Female participants of childbearing potential and male participants with female partners of childbearing potential had to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
排除标准
- •A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency (activity < 5%).
- •Shiga toxin-related hemolytic uremic syndrome.
- •Positive direct Coombs test.
- •Pregnancy or breastfeeding.
- •Identified drug exposure-related hemolytic uremic syndrome (HUS).
- •Bone marrow transplant/hematopoietic stem cell transplant within last 6 months prior to start of Screening.
- •HUS related to known genetic defects of cobalamin C metabolism.
- •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).
研究组 & 干预措施
Ravulizumab
Participants were administered weight-based doses of ravulizumab every 8 weeks for 26 weeks in the Initial Evaluation Period.
After the Initial Evaluation Period, participants could enter an Extension Period and receive ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.
干预措施: Ravulizumab (Biological)
结局指标
主要结局
Percentage Of 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. The percentage was based on the responders among treated participants. The 95% confidence interval (CI) was based on the asymptotic Gaussian approximation method with a continuity correction.
次要结局
- Change From Baseline In Quality Of Life As Measured By The EuroQol 5-Dimension 3-Level (EQ-5D-3L) At Weeks 26 and 52(Baseline, Week 26 and Week 52)
- Time To Complete TMA Response(Baseline through Week 114)
- Proportion Of Participants With Complete TMA Response At Week 52(Week 52)
- Participants With Change From Baseline In CKD Stage 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)
- Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Weeks 26 and 52(Baseline, Week 26 and Week 52)
- Change From Baseline In LDH 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)
- Change From Baseline In Platelet Count 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 Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire At Weeks 26 and 52(Baseline, Week 26 and Week 52)