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Trial record 1 of 1 for:    NCT04082260
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Signatures of Immune Reprogramming in Anti-CD52 Therapy of MS: Markers for Risk Stratification and Treatment Response (ProgramMS)

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ClinicalTrials.gov Identifier: NCT04082260
Recruitment Status : Recruiting
First Posted : September 9, 2019
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Multiple Sclerosis Drug: Alemtuzumab Injection [Lemtrada]

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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Signatures of Immune Reprogramming in Anti-CD52 Therapy of MS: Markers for Risk Stratification and Treatment Response
Actual Study Start Date : January 2017
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Alemtuzumab

Group/Cohort Intervention/treatment
De novo patients with alemtuzumab
De novo patients prior and after alemtuzumab treatment initiation
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.


Alemtuzumab treatment
Patients under alemtuzumab treatment
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.


Extended alemtuzumab treatment
Patients requiring more than two alemtuzumab infusions
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.





Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Change from baseline in levels of markers of autoimmunity (ANA, cANCA and pANCA) in the serum (every 6 months): [ Time Frame: 36 month ]
    - IFT (immunoflescence-test) of ANA, cANCA and pANCA

  7. Change from baseline in levels of markers of autoimmunity (anti-dsDNA) in the serum (every 6 months): [ Time Frame: 36 month ]
    - RIA (radioimmunoassay) of anti-dsDNA

  8. Change from baseline in levels of markers of autoimmunity (anti-TSH-Receptor) in the serum (every 6 months): [ Time Frame: 36 month ]
    - Levels of anti-TSH-Receptor (U/ml)

  9. Change from baseline in levels of markers of autoimmunity(anti-TPO) in the serum (every 6 months): [ Time Frame: 36 month ]
    - Levels of anti-TPO (U/ml)

  10. Change from baseline in levels of markers of autoimmunity (Rheumatoid factor) in the serum (every 6 months): [ Time Frame: 36 month ]
    - Levels of Rheumatoid factor (U/ml)

  11. Change from baseline in levels of markers of autoimmunity (anti-CCP) in the serum (every 6 months): [ Time Frame: 36 month ]
    - Levels of anti-CCP (U/ml)

  12. Change from baseline in levels of markers of autoimmunity (anti-GBM) in the serum (every 6 months): [ Time Frame: 36 month ]
    - Levels of anti-GBM (U/ml)

  13. Change from baseline in levels of markers of autoimmunity (antiplatelet antibodies) in the serum (every 6 months): [ Time Frame: 36 month ]
    - Levels of antiplatelet antibodies (U/ml)


Secondary Outcome Measures :
  1. Functional characterization of T-cells and B cells in the peripheral blood (every 6 months) [ Time Frame: 36 month ]

Other Outcome Measures:
  1. Clinical related data: Analysis of MRI scans [ Time Frame: 36 month ]
    - Number and location of lesions in MRI scans will be count

  2. Clinical related data: Evaluation of disease activity and manifestation (EDSS) in comparison to baseline (every 6 months) [ Time Frame: 36 month ]

    • Expanded Disability Status Scale (EDSS):

    • Scoring will be performed using standard scoring test from www.neurostatus.net.
    • EDSS is an ordinal clinical rating scale which ranges from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. EDSS steps 1.0 to 4.5 refer to people with MS who are fully ambulatory, while EDSS steps 5.0 to 9.5 are defined by the impairment to ambulation.

  3. Clinical related data: Evaluation of disease activity and manifestation (MSFC) in comparison to baseline (every 6 months) [ Time Frame: 36 month ]

    • Multiple Sclerosis Functional Composite (MSFC):

    • MSFC will be administered according to the MSFC manual of the National MS Society.
    • In brief measurements on the impact of MS in three key clinical dimensions: leg function and ambulation, arm and hand function, and cognitive function are done. Raw scores in different measurement scales are transformed into standard comparable scores (z-scores) and an overall composite score is calculated.

  4. Clinical related data: Observation of relapse rates [ Time Frame: 36 month ]
    - Number and time of relapses will be counted



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04082260


Contacts
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Contact: Tobias Ruck, Dr.med. tobias.ruck@ukmuenster.de

Locations
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Germany
Department of Neurology Recruiting
Münster, NRW, Germany, 48149
Contact: Tobias Ruck       tobias.ruck@ukmuenster.de   
Sponsors and Collaborators
University Hospital Muenster
Investigators
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Principal Investigator: Sven Meuth, Prof. Department of Neurology with Institute of Translational Neurology, University Hospital Muenster

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Responsible Party: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT04082260    
Other Study ID Numbers: ProgramMS2017
First Posted: September 9, 2019    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Alemtuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents