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

• Conditions: Multiple Sclerosis
• Interventions: Drug: Alemtuzumab Injection [Lemtrada]

• Registration Number: NCT04082260
• Lead Sponsor: University Hospital Muenster

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01
• Status Verified: 2019-08
• Study First Submitted: 2019-08-28
• Study First Submitted QC: 2019-09-05
• Study First Posted: 2019-09-09
• Last Update Submitted: 2019-09-18
• Last Update Posted: 2019-09-20
• Primary Completion: 2022-01
• Study Completion: 2022-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Extended alemtuzumab treatment	Alemtuzumab Injection [Lemtrada]	Patients requiring more than two alemtuzumab infusions
Alemtuzumab treatment	Alemtuzumab Injection [Lemtrada]	Patients under alemtuzumab treatment
De novo patients with alemtuzumab	Alemtuzumab Injection [Lemtrada]	De novo patients prior and after alemtuzumab treatment initiation

Primary Outcome Measures

Name	Time	Method
Absolute and relative change of cell-counts compared to baseline of T cell subsets in the peripheral blood (every 6 months)	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):	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):	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):	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)	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)	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)	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)	36 month	• Myeloid-derived suppressor cells
Change from baseline in levels of markers of autoimmunity (antiplatelet antibodies) in the serum (every 6 months):	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):	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):	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):	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):	36 month	- Levels of Rheumatoid factor (U/ml)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Neurology; 🇩🇪 Münster, NRW, Germany