Safety and Efficacy of a Therapy With Cladribine Following a Treatment With Anti CD20 Compounds in Relapsing Multiple Sclerosis Patients: a Pilot Study
试验速览
- 阶段
- 不适用
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Changes in IgG serum concentrations in Cald-Group
研究概览
简要总结
Prolonged anti CD20 therapy for the treatment of active multiple sclerosis leading to continuous B cell depletion is associated with hypogammaglobulinemia predisposing to a potentially increased risk of serious infections, particularly in the more disabled and aged patients. No data have been published on the sequential use of anti CD20 therapies and cladribine, that is thought to act as an immune reconstitution agent. his study aims at investigating IgG and IgM serum concentration changes at 6 and 12 months after switching to cladribine in patients previously treated with anti CD20 therapies (ie, ocrelizumab ≥1.8 gr or rituximab 3.0 gr) for ≥18 months, as compared to continued anti CD20 therapies.
详细描述
The study population will include patients with remitting relapsing multiple sclerosis consulting the Multiple Sclerosis Center of Neurocenter of Southern Switzerland.
Enrolled patients will have 5 Study Visits, one every 3 months according to clinical practice. At visits at 3 and 6 months only adverse events will be collected for study purposes. Clinical assessments will be performed at baseline, Month 6 and Month 12. Clinical assessments correspond to medical exams performed routinely in MS patients treated with anti CD20 or cladribine therapy: clinical assessments, monitoring haemoglobin parameters, serum immunoglobulins, liver and renal function.(6, 12 months), radiological disability progression and biomarker of ongoing neurodegeneration (12 months).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsing MS according to Lublin;
- •Treatment with ocrelizumab or rituximab for ≥18 months and having received 1.8 / 3.0 gr, respectively;
- •CLAD_GROUP: Planning to switch to cladribine because of concerns about increased risks of infections related to hypogammaglobulinemia developing during long term anti CD20 therapies or a documented decrease of ≥10% IgG and/or IgM compared to pre- anti CD20 therapy;
- •or CD20_GROUP: no need to stop CD20 therapy due decrease of ≥10% IgG and/or IgM, or increased risk of infections related to hypogammaglobulinemia or other reasons, continued anti CD20 therapies clinically indicated;
- •EDSS ≤7.0;
- •Age >18 years.
排除标准
- •Non relapsing MS;
- •Pregnancy - breastfeeding;
- •Contraindications to perform MRI;
- •Contraindication to receive cladribine or to continue anti CD therapies
研究组 & 干预措施
CLAD-GROUP
Patients with cladribine therapy
干预措施: Cladribine Oral Tablet (Drug)
CD20-GROUP
Patients with anti CD20 therapy (ocrelizumab or rituximab)
干预措施: Rituximab (Drug)
CD20-GROUP
Patients with anti CD20 therapy (ocrelizumab or rituximab)
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Changes in IgG serum concentrations in Cald-Group
时间窗: 6 months
Standard laboratory test
Changes in IgM serum concentrations in Cald-Group
时间窗: 6 months
Standard laboratory test
Changes in IgM serum concentrations in Clad-Group
时间窗: 12 months
Standard laboratory test
Changes in IgG serum concentrations in Clad-Group
时间窗: 12 months
Standard laboratory test
次要结局
- Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies(12 months)
- Number/volume of cumulative new T2/ enlarging lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies(12 months)
- Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies(12 months)
- Number/volume of cumulative Gd enhancing lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies(12 months)
- Changes in serum neurofilament light chain concentration(12 months)
- Annualized relapse rate (ARR) over 12 months after switching to cladribine as compared to patients continuing anti CD20 therapies(12 months)
- Proportion of patients with disability progression(12 months)
- Proportion of patients reaching NEDA -3(12 months)
研究者
Claudio Gobbi
Head Physician
Ospedale Civico, Lugano