NCT04082260

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
150

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jan 2017

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2017

Completed
2.7 years until next milestone

First Submitted

Initial submission to the registry

August 28, 2019

Completed
12 days until next milestone

First Posted

Study publicly available on registry

September 9, 2019

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2022

Completed
Last Updated

September 20, 2019

Status Verified

August 1, 2019

Enrollment Period

5 years

First QC Date

August 28, 2019

Last Update Submit

September 18, 2019

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (13)

  • Absolute and relative change of cell-counts compared to baseline of T cell subsets in the peripheral blood (every 6 months)

    • 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

    36 month

  • Absolute and relative change of cell-counts compared to baseline of B-cell subsets in the peripheral blood (every 6 months)

    • B cell subsets: * Recent bone marrow emigrants, mature naïve, memory B cells * Plasma cells

    36 month

  • Absolute and relative change of cell-counts compared to baseline of natural killer cells in the peripheral blood (every 6 months)

    • Natural killer cells: * CD56bright, CD56dim * Natural killer T cells

    36 month

  • Absolute and relative change of cell-counts compared to baseline of antigen-presenting cells in the peripheral blood (every 6 months)

    • Antigen-presenting cells: * Dendritic cells: CD303+ plasmacytoid, CD11c+ and CD141+ myeloid dendritic cells * Monocytes and macrophages

    36 month

  • Absolute and relative change of cell-counts compared to baseline of myeloid-derived suppressor cells in the peripheral blood (every 6 months)

    • Myeloid-derived suppressor cells

    36 month

  • Change from baseline in levels of markers of autoimmunity (ANA, cANCA and pANCA) in the serum (every 6 months):

    \- IFT (immunoflescence-test) of ANA, cANCA and pANCA

    36 month

  • Change from baseline in levels of markers of autoimmunity (anti-dsDNA) in the serum (every 6 months):

    \- RIA (radioimmunoassay) of anti-dsDNA

    36 month

  • Change from baseline in levels of markers of autoimmunity (anti-TSH-Receptor) in the serum (every 6 months):

    \- Levels of anti-TSH-Receptor (U/ml)

    36 month

  • Change from baseline in levels of markers of autoimmunity(anti-TPO) in the serum (every 6 months):

    \- Levels of anti-TPO (U/ml)

    36 month

  • Change from baseline in levels of markers of autoimmunity (Rheumatoid factor) in the serum (every 6 months):

    \- Levels of Rheumatoid factor (U/ml)

    36 month

  • Change from baseline in levels of markers of autoimmunity (anti-CCP) in the serum (every 6 months):

    \- Levels of anti-CCP (U/ml)

    36 month

  • Change from baseline in levels of markers of autoimmunity (anti-GBM) in the serum (every 6 months):

    \- Levels of anti-GBM (U/ml)

    36 month

  • Change from baseline in levels of markers of autoimmunity (antiplatelet antibodies) in the serum (every 6 months):

    \- Levels of antiplatelet antibodies (U/ml)

    36 month

Secondary Outcomes (1)

  • Functional characterization of T-cells and B cells in the peripheral blood (every 6 months)

    36 month

Other Outcomes (4)

  • Clinical related data: Analysis of MRI scans

    36 month

  • Clinical related data: Evaluation of disease activity and manifestation (EDSS) in comparison to baseline (every 6 months)

    36 month

  • Clinical related data: Evaluation of disease activity and manifestation (MSFC) in comparison to baseline (every 6 months)

    36 month

  • +1 more other outcomes

Study Arms (3)

De novo patients with alemtuzumab

De novo patients prior and after alemtuzumab treatment initiation

Drug: Alemtuzumab Injection [Lemtrada]

Alemtuzumab treatment

Patients under alemtuzumab treatment

Drug: Alemtuzumab Injection [Lemtrada]

Extended alemtuzumab treatment

Patients requiring more than two alemtuzumab infusions

Drug: Alemtuzumab Injection [Lemtrada]

Interventions

Alemtuzumab Injection [Lemtrada]DRUG

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 treatmentDe novo patients with alemtuzumabExtended alemtuzumab treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

The patient population will be patients with active RRMS, which will be rectruited in multiple KKNMS (Kompetenznetz Multiple Sklerose) centres.

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Neurology

Münster, North Rhine-Westphalia, 48149, Germany

RECRUITING

Related Publications (1)

  • 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.

    PMID: 33324905DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Sven Meuth, Prof.

    Department of Neurology with Institute of Translational Neurology, University Hospital Muenster

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobias Ruck, Dr.med.

CONTACT

tobias.ruck@ukmuenster.de

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 28, 2019

First Posted

September 9, 2019

Study Start

January 1, 2017

Primary Completion

January 1, 2022

Study Completion

January 1, 2022

Last Updated

September 20, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will not share

Locations

DE(1)