Signatures of Immune Reprogramming in Anti-CD52 Therapy of MS: Markers for Risk Stratification and Treatment Response
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Absolute and relative change of cell-counts compared to baseline of T cell subsets in the peripheral blood (every 6 months)
研究概览
简要总结
Alemtuzumab is a highly effective therapy in relapse remitting multiple sclerosis (RRMS). The aim of this study is to elucidate the mechanism of action of the neuroprotective potential of alemtuzumab in RRMS. Therefore, the investigators will semi-annually analyse blood samples of RRMS patients treated with alemtuzumab up to 36 months. Using in vitro/ ex vivo assays the investigators aim to detect and characterize immune cells including their functional activity. Furthermore, the study aims to combine this analysis with clinical data (MRI, EDSS: Expanded Disability Status Scale, MSFC: Multiple Sclerosis Functional Composite) to reveal the underlining mechanism of action of alemtuzumab to further improve its efficacy and safety for present and future patients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of MS according to the McDonald criteria 2010 and cranial MRI scan demonstrating white matter lesions attributable to MS within 5 years before prior to signing the informed consent form (ICF)
- •Age > 18 years
- •Written informed consent to study participation
排除标准
- •Medical, psychiatric, cognitive, or other conditions that, in the Investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, or to complete the study
- •Any progressive form of MS
- •Any condition that serves as a contraindication for alemtuzumab treatment
- •Any disability acquired from trauma or another illness that could interfere with the evaluation of disability due to MS
- •Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results, e.g., current peptic ulcer disease or other conditions that may predispose to hemorrhage
- •Significant autoimmune disease including but not limited to immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis
- •Inability to undergo MRI with gadolinium administration
研究组 & 干预措施
De novo patients with alemtuzumab
De novo patients prior and after alemtuzumab treatment initiation
干预措施: Alemtuzumab Injection [Lemtrada] (Drug)
Alemtuzumab treatment
Patients under alemtuzumab treatment
干预措施: Alemtuzumab Injection [Lemtrada] (Drug)
Extended alemtuzumab treatment
Patients requiring more than two alemtuzumab infusions
干预措施: Alemtuzumab Injection [Lemtrada] (Drug)
结局指标
主要结局
Absolute and relative change of cell-counts compared to baseline of T cell subsets in the peripheral blood (every 6 months)
时间窗: 36 month
• T cell subsets: * CD (cluster of differentiation) 4 and CD8 positive T cells: naïve T cells, T effector cells, T memory cells, regulatory T cells * T-helper subsets: Th1, Th2, Th17
Change from baseline in levels of markers of autoimmunity (ANA, cANCA and pANCA) in the serum (every 6 months):
时间窗: 36 month
- IFT (immunoflescence-test) of ANA, cANCA and pANCA
Change from baseline in levels of markers of autoimmunity (anti-dsDNA) in the serum (every 6 months):
时间窗: 36 month
- RIA (radioimmunoassay) of anti-dsDNA
Change from baseline in levels of markers of autoimmunity (anti-TSH-Receptor) in the serum (every 6 months):
时间窗: 36 month
- Levels of anti-TSH-Receptor (U/ml)
Absolute and relative change of cell-counts compared to baseline of natural killer cells in the peripheral blood (every 6 months)
时间窗: 36 month
• Natural killer cells: * CD56bright, CD56dim * Natural killer T cells
Absolute and relative change of cell-counts compared to baseline of B-cell subsets in the peripheral blood (every 6 months)
时间窗: 36 month
• B cell subsets: * Recent bone marrow emigrants, mature naïve, memory B cells * Plasma cells
Absolute and relative change of cell-counts compared to baseline of antigen-presenting cells in the peripheral blood (every 6 months)
时间窗: 36 month
• Antigen-presenting cells: * Dendritic cells: CD303+ plasmacytoid, CD11c+ and CD141+ myeloid dendritic cells * Monocytes and macrophages
Absolute and relative change of cell-counts compared to baseline of myeloid-derived suppressor cells in the peripheral blood (every 6 months)
时间窗: 36 month
• Myeloid-derived suppressor cells
Change from baseline in levels of markers of autoimmunity (antiplatelet antibodies) in the serum (every 6 months):
时间窗: 36 month
- Levels of antiplatelet antibodies (U/ml)
Change from baseline in levels of markers of autoimmunity(anti-TPO) in the serum (every 6 months):
时间窗: 36 month
- Levels of anti-TPO (U/ml)
Change from baseline in levels of markers of autoimmunity (anti-CCP) in the serum (every 6 months):
时间窗: 36 month
- Levels of anti-CCP (U/ml)
Change from baseline in levels of markers of autoimmunity (anti-GBM) in the serum (every 6 months):
时间窗: 36 month
- Levels of anti-GBM (U/ml)
Change from baseline in levels of markers of autoimmunity (Rheumatoid factor) in the serum (every 6 months):
时间窗: 36 month
- Levels of Rheumatoid factor (U/ml)
次要结局
- Functional characterization of T-cells and B cells in the peripheral blood (every 6 months)(36 month)