Norwegian Study of Oral Cladribine and Rituximab in Multiple Sclerosis (NOR-MS) A Prospective Randomized Open-label Blinded Endpoint (PROBE) Multicenter Non-inferiority Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 267
- 试验地点
- 11
- 主要终点
- Number of new or enlarging cerebral MRI T2 lesions
研究概览
简要总结
The main aim and overall objective of the study is to assess whether rituximab is non-inferior to cladribine for the treatment of relapsing MS. Secondly, the investigators will test specific blood and MRI biomarkers that may contribute to future personalized treatment for MS patients. Furthermore, the investigators want to evaluate the health economic consequences of the two therapies.
详细描述
Multiple sclerosis (MS) is a demyelinating and neurodegenerative inflammatory disease of the central nervous system, affecting more than 12 000 patients in Norway and more than 2.2 mill patients worldwide.
Oral cladribine is one of the first choices for highly efficient disease modulatory treatment (DMT), while Rituximab is used off-label as DMT in relapsing MS. Large observational studies indicate good tolerance and treatment effect of rituximab in MS and studies from other diseases indicate a good safety profile. However, no phase 3 studies have been performed to test whether rituximab is as efficient as established MS treatments. Formal safety data is also lacking for the treatment with rituximab in MS.
The investigators will perform a prospective randomized open-label blinded endpoint multicenter non-inferiority study. The primary objective is to test whether rituximab is non-inferior to oral cladribine in the treatment of relapsing MS. 264 MS patients aged 18-65 years with relapsing MS will be recruited from 10 centers and followed for 96 weeks. The primary endpoint is difference in new T2 lesions between the groups. Furthermore, the investigators will test novel blood sample and MRI biomarkers to provide tools for personalized MS treatments. Finally, the health economic consequences of these treatment options will be evaluated.
This study will guide clinicians and patients in the future treatment choice for MS and can potentially make a huge impact on the costs of future MS treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Two independent blinded radiologists assess the primary endpoint, New or enlarging T2 lesions. The blinding is asserted by transfer of deidentified MRIs to a Research server, from where the assessment is performed, so that the radiologists know only the ID, not the treatment allocation of the patients from whom the assess MRIs.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 65 years
- •A diagnosis of relapsing MS according to the 2017 McDonald criteria
- •Disease activity seen as either a clinical relapse or MRI activity during the last 12 months
- •EDSS between 0 and 5.5
- •Thrombocytes and leukocytes within normal range, and lymphocytes above 0.8 x10 9/L before first dose of study medication
- •A) For women of childbearing potential: accepting to use adequate contraception in the trial period. If randomized to cladribine, women who use systemic hormonal contraception must accept to use additional barrier contraception during each treatment cycle and for four weeks after each treatment cycle.
- •B) For men: If randomized to cladribine, accepting to use adequate contraception in the safety period of 6 months after each treatment cycle.
- •Able to understand written and spoken Norwegian or English
- •Able to complete treatment or follow-ups in the study (e.g. no contraindications for MRI, severe psychiatric disease, drug abuse or plans of moving)
- •Signed informed consent
排除标准
- •Any contraindication or increased risk of side-effects from rituximab or cladribine (such as ongoing acute or chronic infection, live vaccination less than 4 weeks before start of treatment or planned live vaccination, immunocompromised, previous or active malignant disease, ongoing glucocorticoid treatment or allergy against any products of the medication)
- •Previous use of any of cladribine, rituximab, alemtuzumab, ocrelizumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression with long lasting effects
- •Fingolimod or natalizumab treatment within the last six months before inclusion
- •Current pregnancy or lactation
研究组 & 干预措施
Rituximab
Biosimilar rituximab concentrate for solution for infusion
干预措施: Rituximab (Biological)
Cladribine
Mavenclad oral cladribine tablets
干预措施: Cladribine (Drug)
结局指标
主要结局
Number of new or enlarging cerebral MRI T2 lesions
时间窗: Week 12-96
The primary outcome is the number of new or enlarging cerebral MRI T2 lesions per patient from week 12 to week 96
次要结局
- Relapse-free patients(Week -2 to 96)
- T2 lesions after 48 weeks(Week 12-48)
- Annual clinical relapse rate (ARR)(Week -2 to 96)
- Change in disability(Week -2 to 96)
- Disability progression(Week -2 to 96)
研究者
Gro Owren Nygaard
Gro Owren Nygaard, MD, PhD
Oslo University Hospital