Oral Cladribine B-cell Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Percent Change in Class-switched Memory B Cells From Baseline to Week 96 nh
研究概览
简要总结
To study the impact of cladribine on peripheral and intrathecal B-cell, plasma cells, T cells and Tregs
详细描述
Primary: To quantify the temporal changes of memory B cells (CD19+/CD27+/IgD-/+), plasmablasts (CD19-/CD138+/CD38+) and T cells (CD4/CD45RA-/+, CCR7-/+, CD8+/CD45RA-/+/CCR7-/+), Tregs (CD4/CD8)/CD25+/CD127-/Fox3 P+) in the peripheral venous blood of pwMS with RRMS over 96w of treatment with oral cladribine.
These will be compared to the populations of non-memory or class-switched B cells (immature/transitional B cells CD10+/CD38+/CD19+, immature regulatory B cells CD10+/CD38+/CD19+/CD24+/IL-10+, mature B cells CD10-/CD38+/CD19+).
Secondary:
-
To study the effects of oral cladribine on:
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CSF OCBs and free immunoglobulin kappa and lambda light chain levels (FLC).
-
CSF markers of inflammation, in particular CXCL-13 and urine markers of inflammation (neopterin).
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CSF markers of neuroaxonal damage, in particular free neurofilament light chains.
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On the peripheral repertoire B-cells (immunoglobulin) and T-cells (T cell receptor) and plasma cells (soluble receptors).
-
To compare CSF OCB positivity and CSF light chain levels with a contemporary control group of alemtuzumab treated pwMS (historical data).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with MS who are being treated with oral cladribine at Barts Health NHS Trust will be approached to participate in this study.
- •Patients must be willing and able to undergo lumbar punctures
- •Patients who are OCB positive in their CSF (previous diagnostic lumbar puncture)
排除标准
- •Ineligible for oral cladribine under NHS England prescribing guidelines and those participating in MAGNIFY-MS study (cladribine tablets in active MS)
- •Unsuitable to have a lumbar puncture, for example spinal deformity, tethered cord syndrome or the use of aspirin or anticoagulants, and those unable to comply with study requirements, including frequency of visits and lumbar punctures.
- •Presence of comorbidities in which the administration of cladribine is contraindicated.
- •Abnormal baseline investigations (WBC<3 x 10*9/l, lymphocytes <1.0 x 10*9/l, neutrophil count <1.5 x 10*9/l, platelet count <100 x 10*9, haemoglobin <110g/l, LFT>/3x upper limit of normal of site reference ranges, potassium <2.8mmol/l or >5.5mmol/l, sodium <125 mmol/l, creatinine >130 umol/l)
研究组 & 干预措施
Cladribine (Mavenclad, Merck Serono Ltd)
In the summary of product characteristics the recommended cumulative dose is 3.5 mg/kg body weight over 2 years, taken as 1 treatment course of 1.75 mg/kg per year. Each treatment course consists of 2 treatment weeks, 1 at the beginning of the first month and 1 at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient takes 10 mg or 20 mg (1 or 2 tablets) as a single daily dose, depending on body weight
结局指标
主要结局
Percent Change in Class-switched Memory B Cells From Baseline to Week 96 nh
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in class-switched memory B cells (CD19+/CD27+/IgD-) in participants with RRMS treated with oral cladribine.
Percent Change in Non Class-switched Memory B Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in non class-switched memory B cells (CD19+/CD27+/IgD+) in participants with RRMS treated with oral cladribine.
Percent Change in Plasmablast From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in plasmablasts (CD19+/CD27+/CD38+) in participants with RRMS treated with oral cladribine.
Percent Change in Transitional B Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in transitional B cells (CD19+ IgD+ CD10+ CD27-) in participants with RRMS treated with oral cladribine.
Percent Change in Regulatory B Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in regulatory B cells (CD19+/CD24+/CD38+) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ Central Memory T Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ central memory T cells (CD45RA- CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ Naive T Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ naive T cells (CD45RA+ CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ TEMRA Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ TEMRA cells (CD45RA+ CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in CD4+ Effector Memory T Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD4+ effector memory T cells (CD45RA- CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ Central Memory T Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ central memory T cells (CD45RA- CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ Naive T Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ naive T cells (CD45RA+ CCR7+) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ TEMRA Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ TEMRA cells (CD45RA+ CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in CD8+ TEM Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in CD8+ effector memory T cells (CD45RA- CCR7-) in participants with RRMS treated with oral cladribine.
Percent Change in Regulatory T Cells From Baseline to Week 96
时间窗: Baseline to week 96
Percent change from baseline to Week 96 in regulatory T cells (CD4+ CD25+ FOXP3+) in participants with RRMS treated with oral cladribine.
次要结局
- Changes in CSF of κ Free Light Chain (KFLC) From Baseline to Week 48 and Week 96(Baseline to week 96)
- Change in CSF Oligoclonal Band (OCB) Positivity From Baseline to Week 48 and Week 96(Baseline to week 96)
- Changes in CSF of λ Free Light Chain (LFLC) Index From Baseline to Week 48 and Week 96(Baseline to week 96)
- Change in CSF CXCL-13 Levels From Baseline to Week 96(Baseline to week 96)
- Change in Urine Neopterin Levels From Baseline to Week 96(Baseline to week 96)
- Change in CSF Neurofilament Light Chain (NfL) Levels From Baseline to Week 96(Baseline to 96 weeks)
- Change in CSF Soluble CD138 Levels From Baseline to Week 96(Baseline to week 96)
- Changes in CSF Cytokine and Chemokine Levels From Baseline to Week 96(Baseline to week 96)