A Phase 2/3 Open-Label, Single-Arm Trial to Evaluate the Safety and Activity of Eculizumab in Pediatric Patients With Relapsing Neuromyelitis Optica Spectrum Disorder
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Change Between the Baseline Annualized Relapse Rate (ARR) and the On-Trial ARR at Week 52/53
研究概览
简要总结
The objective of this study is to evaluate the safety and efficacy of eculizumab in pediatric participants (aged 2 to < 18 years) with relapsing neuromyelitis optica spectrum disorder (NMOSD).
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
- •Male or female participants aged 2 years to < 18 years with body weight ≥ 10 kilograms (kg).
- •Vaccinated against Neisseria meningitidis within 3 years prior to, or at the time of initiating eculizumab. Participants who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics until 2 weeks after the vaccination.
- •Documented vaccination against haemophilus influenzae type b and streptococcus pneumoniae infections at least 2 weeks prior to dosing as per local and country-specific immunization guidelines for the appropriate age group.
- •Anti-aquaporin-4 antibody-positive and diagnosis of NMOSD as defined by the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria.
- •Historical Relapse Rate of at least 2 relapses in the last 2 years, and with at least 1 relapse in the year prior to Screening.
- •EDSS score ≤
- •Participants who enter the study receiving supportive immunosuppressive therapies (ISTs) for the prevention of relapse, either in combination or monotherapy, must be on a stable dosing regimen of adequate duration.
- •Female participants of childbearing potential must have a negative pregnancy test (serum human chorionic gonadotropin) at Screening and follow protocol-specified contraception guidance for avoiding pregnancy while on treatment and for 5 months after the last dose of eculizumab.
- •Male participants with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner must agree to use double barrier contraception (male condom plus appropriate barrier method for the female partner) while on treatment and for at least 5 months after the last dose of eculizumab.
排除标准
- •Parent or legal guardian is an Alexion employee.
- •Pregnant, breastfeeding, or intending to conceive during the course of the study.
- •Participants known to be human immunodeficiency virus positive or with congenital immunodeficiency.
- •Unresolved meningococcal or other serious infection.
- •Any unresolved acute or chronic systemic bacterial or other infection that is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics.
- •Use of rituximab or other biologicals such as tocilizumab within 6 months prior to Screening.
- •Use of mitoxantrone within 3 months prior to Screening.
- •Use of intravenous immunoglobulin or plasma exchange within 3 weeks prior to Screening.
- •Use of immunomodulatory therapies for multiple sclerosis within 3 months prior to Screening.
- •Has previously received treatment with eculizumab or other complement inhibitors.
研究组 & 干预措施
Eculizumab
All participants will receive open-label eculizumab by intravenous infusion during the Primary Treatment Period, starting on Day 1 and for a total of 52/53 weeks. The dosing regimen will be based on the participant's body weight. As body weight changes during the study, the participant's weight cohort and dose may change accordingly.
After completing the 52/53-week Primary Treatment Period, participants may continue receiving eculizumab in the Extension Treatment Period for 104 weeks.
干预措施: Eculizumab (Drug)
结局指标
主要结局
Change Between the Baseline Annualized Relapse Rate (ARR) and the On-Trial ARR at Week 52/53
时间窗: Baseline, Week 52/53
ARR was calculated as the number of relapses for each participant divided by the number of years of treatment for that participant. Baseline ARR was based on 24 months prior to screening.
Time to First On-trial Relapse
时间窗: Baseline up to Week 52/53
Time to First Relapse was defined as beginning at the time the participant's first dose of eculizumab was administered until the participant's first on-trial relapse was reported by the Investigator. Participants who did not experience an on-trial relapse were censored at the end of the study period.
次要结局
- Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 52/53(Baseline, Week 52/53)
- Change From Baseline in the Hauser Ambulation Index (HAI) Score at Week 52/53(Baseline, Weeks 52/53)
- Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Score at Week 52/53(Baseline, Weeks 52/53)
- Number of Participants With Shift From Baseline in Visual Acuity (VA)(Baseline, Week 52/53)
- Number of Participants With Shift From Baseline in Confrontational Visual Fields (VF)(Baseline, Weeks 52/53)
- Number of Participants With Shift From Baseline in Color Vision(Baseline, Weeks 52/53)
- Serum Eculizumab Concentration at Week 52(Week 52)
- Change From Baseline in Serum Free Complement Protein 5 (C5) Concentrations at Week 52(Baseline, Week 52)