Understanding the 'Durable Effect' Concept of B-cell Modulating Therapies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change from baseline in the peripheral immune cell profile
研究概览
简要总结
This prospective, observational clinical study aims to longitudinally assess peripheral immune cell profiles of patients with relapsing-remitting multiple sclerosis (RRMS) receiving anti-CD20 therapy with ofatumumab (OFA), ocrelizumab (OCR), ublituximab (UBX), and rituximab (RTX). Throughout the study, clinical data - including relapse events, patient scores, and neuropsychological parameters - will be collected, along with results from imaging techniques such as Optical Coherence Tomography (OCT) and Magnetic Resonance Imaging (MRI). This clinical data will be combined with immunological analyses, including multidimensional flow cytometry (mFC), bulk RNA sequencing (bulk-Seq), T and B cell receptor sequencing (TCR/BCR-Seq), proteomics, and immunoglobulin analysis. This approach aims to enable a detailed characterization of changes in the immune cell repertoire and their impact on the clinical disease course.
详细描述
B cell targeted therapies have become a key element in the treatment of multiple sclerosis due to their effectiveness in rapid and long-lasting depletion of B cells in peripheral blood (PB), significantly reducing relapse rates and disability progression. The monoclonal antibodies OFA, OCR, UBX, and RTX target the B cell surface protein CD20, however it is unclear how B cell depletion and subsequent repopulation allows for immune system reconstitution and how other immune cell populations are affected by these therapies. Furthermore, the relevance of immune cell changes - beyond B cell depletion - for clinical disease stability remains insufficiently understood.
By collecting comprehensive and structured prospective clinical data alongside immunological analyses, this study aims for a better understanding of immunological changes in RRMS patients receiving anti-CD20 therapies and the implications of those alterations in immune cell profiles on the clinical disease course. REBELLION-MS plans for two patient cohorts: cohort 1 (C1; basic cohort) and cohort 2 (C2; in-depth cohort). Participants in C1 will be seen every 6 months up until month 24, then every 12 months. The following parameters will be collected: demographic data, disease characteristics incl. Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) data, serum samples, and Peripheral Blood Mononuclear Cells (PBMCs). Furthermore, Short Form-36 (SF-36) and Fatigue Scale for Motor and Cognitive Functions (FSMC) are documented. Participants of C2 will receive additional evaluations: clinical evaluation incl. EDSS and sampling of serum and PBMCs at months 1 and 3, Multiple sclerosis functional composite (MFSC) every 6 months, and optical coherence tomography (OCT) as well as neuropsychological assessment (NPT) every 12 months. Serum samples and PBMCs will be analyzed by mFC, bulk-Seq, TCR/BCR-Seq, and proteomics, among other methods.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed relapsing-remitting multiple sclerosis (RRMS) according to 2017 revised McDonald criteria
- •Current treatment with B cell modulating therapies or initiation/transition to B cell modulating therapies according to the "Summary of Product Characteristics (SmPC)"
- •EDSS score of 0.0 to 7.0
排除标准
- •Previous treatment with alemtuzumab, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation or bone marrow transplantation
- •Medical, psychiatric, cognitive, or other conditions that, in the opinion of the investigator, impair the patient's ability to understand the patient information and give informed consent
- •Patients receiving immunosuppressive treatment for conditions other than MS or long-term corticosteroid treatment
- •Patients with confirmed infection by the Human Immunodeficiency Virus or Hepatitis C Virus
研究组 & 干预措施
Cohort 1 (C1; basic cohort)
Participants will be seen every 6 months up until month 24, then every 12 months. The following parameters will be collected: demographic data, disease characteristics incl. EDSS and MRI data, serum samples, and PBMCs. Furthermore, SF-36 and FSMC are documented.
干预措施: Anti-CD20 antibody (Drug)
Cohort 2 (C2; in-depth cohort)
In addition to the parameters collected for C1, participants of C2 will receive: clinical evaluation incl. EDSS and sampling of serum and PBMCs at months 1 and 3, MFSC every 6 months, and OCT as well as NPT every 12 months.
干预措施: Anti-CD20 antibody (Drug)
结局指标
主要结局
Change from baseline in the peripheral immune cell profile
时间窗: Baseline up to 48 months
Immune cell subpopulations will be analyzed longitudinally by multidimensional flow cytometry \[% of all living cells and mean fluorescent intensity of different cell surface markers\].
Change from baseline in protein profile of the peripheral blood
时间窗: Baseline up to 48 months
Protein expression will be measured longitudinally using proteomics.
Change from baseline in TCR/BCR profile
时间窗: Baseline up to 48 months
T cell and B cell receptor profile will be measured longitudinally using BCR- and TCR-sequencing.
次要结局
- Change from baseline in Expanded Disability Status Scale (EDSS) Score(Baseline up to 48 months)
- Change from baseline in Short Form Health Survey (SF-36)(Baseline up to 48 months)
- Change from baseline on Magnetic Resonance Imaging (MRI)(Baseline up to 48 months)
- Change from baseline in Retinal Nerve Fiber Layer thickness (RNFL)(Baseline up to 48 months)
- Change from baseline in visual acuity (HCV and LCV)(Baseline up to 48 months)
- Change from baseline in Fatigue Scale for Motor and Cognitive Functions (FSMC)(Baseline up to 48 months)
- Change from baseline in Multiple Sclerosis Functional Composite (MSFC) Score(Baseline up to 48 months)
- Change from baseline in Symbol Digit Modalities Test (SDMT)(Baseline up to 48 months)
- Change from baseline in Verbal Memory Learning Test (VMLT)(Baseline up to 48 months)
- Change from baseline in Brief Visuospatial Memory Test (BVMT)(Baseline up to 48 months)
- Change from baseline in Montreal Cognitive Assessment (MoCA)(Baseline up to 48 months)
- Change from baseline in BDI-FS/BDI II(Baseline up to 48 months)
研究者
Univ.-Prof. Dr. med. Dr rer. nat. Sven Meuth
Chairman
Heinrich-Heine University, Duesseldorf