Clinical trial NCT04082260: Signatures of Immune Reprogramming in Anti-CD52 Therapy of MS: Markers for Risk Stratification and Treatment Response
Official title: Signatures of Immune Reprogramming in Anti-CD52 Therapy of MS: Markers for Risk Stratification and Treatment Response
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Sclerosis
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
First posted: 2019-09-09
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The patient population will be patients with active RRMS, which will be rectruited in multiple KKNMS (Kompetenznetz Multiple Sklerose) centres.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Absolute and relative change of cell-counts compared to baseline of T cell subsets in the peripheral blood (every 6 months)
timeFrame: 36 month
measure: Absolute and relative change of cell-counts compared to baseline of B-cell subsets in the peripheral blood (every 6 months)
timeFrame: 36 month
measure: Absolute and relative change of cell-counts compared to baseline of natural killer cells in the peripheral blood (every 6 months)
timeFrame: 36 month
measure: Absolute and relative change of cell-counts compared to baseline of antigen-presenting cells in the peripheral blood (every 6 months)
timeFrame: 36 month
measure: Absolute and relative change of cell-counts compared to baseline of myeloid-derived suppressor cells in the peripheral blood (every 6 months)
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity (ANA, cANCA and pANCA) in the serum (every 6 months):
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity (anti-dsDNA) in the serum (every 6 months):
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity (anti-TSH-Receptor) in the serum (every 6 months):
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity(anti-TPO) in the serum (every 6 months):
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity (Rheumatoid factor) in the serum (every 6 months):
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity (anti-CCP) in the serum (every 6 months):
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity (anti-GBM) in the serum (every 6 months):
timeFrame: 36 month
measure: Change from baseline in levels of markers of autoimmunity (antiplatelet antibodies) in the serum (every 6 months):
timeFrame: 36 month
Secondary outcomes:
measure: Functional characterization of T-cells and B cells in the peripheral blood (every 6 months)
timeFrame: 36 month
Other outcomes:
measure: Clinical related data: Analysis of MRI scans
timeFrame: 36 month
measure: Clinical related data: Evaluation of disease activity and manifestation (EDSS) in comparison to baseline (every 6 months)
timeFrame: 36 month
measure: Clinical related data: Evaluation of disease activity and manifestation (MSFC) in comparison to baseline (every 6 months)
timeFrame: 36 month
measure: Clinical related data: Observation of relapse rates
timeFrame: 36 month
Locations:
city: Münster
country: Germany
facility: Department of Neurology
state: NRW
Study officials:
affiliation: Department of Neurology with Institute of Translational Neurology, University Hospital Muenster
name: Sven Meuth, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bierhansl L, Ruck T, Pfeuffer S, Gross CC, Wiendl H, Meuth SG. Signatures of immune reprogramming in anti-CD52 therapy of MS: markers for risk stratification and treatment response. Neurol Res Pract. 2019 Dec 13;1:40. doi: 10.1186/s42466-019-0045-x. eCollection 2019.