Efficacy, Safety and Cost-effectiveness of B Cell Tailored Ocrelizumab Versus Standard Ocrelizumab in Relapsing Remitting Multiple Sclerosis: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 296
- 试验地点
- 1
- 主要终点
- Confirmed relapse-free patients
研究概览
简要总结
Rationale: B-cell depleting therapies like ocrelizumab are very effective in the treatment of relapsing remitting multiple sclerosis (RRMS). As B cell repopulation varies extensively between individuals (ranging from 27-175 weeks), using a treatment scheme with a fixed infusion interval may be suboptimal. So far personalized adapted treatment of ocrelizumab in RRMS has not been studied in a prospective setting.
Objective: Evaluating the efficacy, safety and cost-effectiveness of ocrelizumab when administered in personalized B cell tailored intervals in RRMS patients.
Study design: This is a national multicenter randomized controlled trial with 96 week follow-up.
Study population: The study population consists of 296 adult RRMS patients who have received ocrelizumab treatment for a minimum of 12 months (2x 300 mg infusion and 1x 600mg infusion).
Intervention: Patients will be randomized into the standard interval group (600 mg infusions every 24 weeks) or the personalized interval group in which the infusions will be extended as long as the serum CD19 B cell count is below 10 CD19 cells/µL, determined every 4 weeks.
Main study parameters: To conclude non-inferiority of personalized B cell tailored ocrelizumab there will be two co-primary endpoints: 1. the difference of percentage of confirmed relapse-free patients between the two groups after 96 weeks and 2. the difference of percentage of patients free from new/enlarging T2 lesions on MRI between the two groups after 96 weeks. Secondary study parameters are number of confirmed relapses, annualized relapse rate, number of new T2 lesions and brain atrophy on MRI, disability progression, no evidence of disease activity (NEDA), MS disease biomarkers (serum neurofilament light), quality of life, burden of treatment, immunoglobulin levels and (serious) adverse events including occurrence of infections and COVID-19. Furthermore, various immune cell subsets will be studied in relation to ocrelizumab concentration in a subgroup.
Nature and extent of the burden and risks: All patients will be subjected to visits every 24 weeks including clinical scoring and questionnaires. Blood samples and MRI scans will be taken and performed every 48 weeks. Continuous assessment of key stroke dynamics on the patients smartphone and monthly digital cognitive test and walk test will be performed in most patients. As CD19 B cells are kept near complete depletion, the estimated risk of recurrence of disease activity is very low.
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A current diagnosis of relapsing remitting multiple sclerosis according to the 2017 McDonald criteria34
- •EDSS score of 0 to 6.5
- •Treatment with ocrelizumab for a minimum of 48 weeks (two 300 mg infusions and one 600 mg infusion)
排除标准
- •Previous treatment with alemtuzumab, cladribine or stem cell transplantation
- •Relapse in the past 3 months prior to inclusion
- •Subsequent treatment with another DMT next to ocrelizumab in the past 6 months prior to inclusion
- •Inability to undergo regular MRI scanning
- •Women who are pregnant or expect to become pregnant during the study period
研究组 & 干预措施
Standard interval dosing
The standard group will receive ocrelizumab every 24 weeks following the current label.
Personalized B cell tailored ocrelizumab treatment
The personalized group will start with B cell measurements 24 weeks after the last infusion (baseline). The infusion interval will never be shorter than 24 weeks. The personalized group will start the study with a possible extension of the interval. The infusion will be postponed as long as CD19 B cell count stays below 10 cells/µL (determined every 4 weeks). When CD19 B cell count exceeds or is equal to 10 cells/µL, ocrelizumab infusion will be scheduled within two weeks
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Confirmed relapse-free patients
时间窗: 96 weeks
Difference of percentage of confirmed relapse-free patients between the two treatment groups after 96 weeks follow-up.
Change of T2 lesions on brain MR
时间窗: 96 weeks
Difference of percentage of patients without new/enlarging T2 MRI lesions between the two treatment groups after 96 weeks follow-up.
次要结局
- Total number of active (new and/or enlarging) T2 lesions on brain MRI(Baseline, year 1, year 2)
- Annualized relapse rate(Baseline, year 1, year 2)
- Disability progression during follow-up(Baseline, year 1, year 2)
- Brain atrophy(Baseline, year 1, year 2)
- NEDA (no evidence of disease activity)(96 weeks)
- Change of neurofilament light(96 weeks)
- Change of quality of life(Baseline, year 1, year 2)
- Change of burden of treatment(Baseline, year 1, year 2)
- Ocrelizumab wearing-off effect(Baseline, year 1, year 2)
- IgG levels(Baseline, year 1, year 2)
- Cost analysis(96 weeks)
- Disability progression: decrease of hand mobility(Baseline, 6 months,12 months, 18 months, 24 months)
- Disability progression: two minute walking distance(Baseline, 6 months,12 months, 18 months, 24 months)
- Disability progression: cognitive impairment(Baseline, 6 months,12 months, 18 months, 24 months)
- Disability progression during follow-up(Baseline, 6 months,12 months, 18 months, 24 months)
研究者
Zoé van Kempen
Principal Investigator
Amsterdam UMC, location VUmc