Signatures of Immune Reprogramming in Anti-CD52 Therapy of MS: Markers for Risk Stratification and Treatment Response

Overview

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.

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: January 2022

Interventions

  • Drug: Alemtuzumab Injection [Lemtrada]
    • Administration of 2 courses of alemtuzumab at an interval of 1 year. Course 1: Intravenous infusion of 12 mg alemtuzumab per day on 5 consecutive days. Course 2: Intravenous infusion of 12 mg alemtuzumab per day on 3 consecutive days.

Arms, Groups and Cohorts

  • De novo patients with alemtuzumab
    • De novo patients prior and after alemtuzumab treatment initiation
  • Alemtuzumab treatment
    • Patients under alemtuzumab treatment
  • Extended alemtuzumab treatment
    • Patients requiring more than two alemtuzumab infusions

Clinical Trial Outcome Measures

Primary Measures

  • Absolute and relative change of cell-counts compared to baseline of T cell subsets in the peripheral blood (every 6 months)
    • Time Frame: 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
  • Absolute and relative change of cell-counts compared to baseline of B-cell subsets in the peripheral blood (every 6 months)
    • Time Frame: 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 natural killer cells in the peripheral blood (every 6 months)
    • Time Frame: 36 month
    • • Natural killer cells: CD56bright, CD56dim Natural killer T cells
  • Absolute and relative change of cell-counts compared to baseline of antigen-presenting cells in the peripheral blood (every 6 months)
    • Time Frame: 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)
    • Time Frame: 36 month
    • • Myeloid-derived suppressor cells
  • Levels of markers of autoimmunity (ANA, cANCA and pANCA) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - IFT (immunoflescence-test) of ANA, cANCA and pANCA
  • Levels of markers of autoimmunity (anti-dsDNA) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - RIA (radioimmunoassay) of anti-dsDNA
  • Levels of markers of autoimmunity (anti-TSH-Receptor) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - Levels of anti-TSH-Receptor (U/ml)
  • Levels of markers of autoimmunity(anti-TPO) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - Levels of anti-TPO (U/ml)
  • Levels of markers of autoimmunity (Rheumatoid factor) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - Levels of Rheumatoid factor (U/ml)
  • Levels of markers of autoimmunity (anti-CCP) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - Levels of anti-CCP (U/ml)
  • Levels of markers of autoimmunity (anti-GBM) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - Levels of anti-GBM (U/ml)
  • Levels of markers of autoimmunity (antiplatelet antibodies) in comparison to basline in the serum (every 6 months):
    • Time Frame: 36 month
    • - Levels of antiplatelet antibodies (U/ml)

Secondary Measures

  • Functional characterization of T-cells and B cells in the peripheral blood (every 6 months)
    • Time Frame: 36 month

Participating in This Clinical Trial

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital Muenster
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Sven Meuth, Prof., Principal Investigator, Department of Neurology with Institute of Translational Neurology, University Hospital Muenster
  • Overall Contact(s)
    • Tobias Ruck, Dr.med., tobias.ruck@ukmuenster.de

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