relapsing-remitting multiple sclerosis MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: LEMTRADA 12 mg Konzentrat zur Herstellung einer Infusionslösung
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Alemtuzumab
CAS Number: 216503-57-0
Other de
Sponsors
Universitätsklinikum Münster
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form (ICF) 2. Age 18 to 55 years old (inclusive) as of the date the ICF is signed 3. Diagnosis of MS according to the McDonald criteria 2010 and cranial MRI scan demonstrating white matter lesions attributable to MS within 10 years before screening 4. Onset of MS symptoms (as determined by a neurologist, either at present or retrospectively) within 10 years of the date the ICF is signed 5. EDSS score 0.0 to 5.0 (inclusive) at Screening 6. Patients with (highly) active RRMS disease course indicated to receive alemtuzumab according to the following conditions (at least 1 out of 3 conditions has to be fulfilled): 1. =2 MS relapses within 24 months 2. clinical (=1 relapse) or MRI (new gadolinium enhancing lesions) disease activity under therapy with other disease-modifying therapies 3. severe relapse with high disease activity (=9 T2 hyperintense Lesions and =1 gadolinium enhancing lesion) on MRI. 7. Completion of all vaccinations required by the applicable immunization guidelines published by “ständige Impfkommission” (STIKO) 8. History of chickenpox or positive test for antibodies against varizella zoster virus (VZV) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical trial at present or within 4 weeks of study entry. There may be exceptions at the discretion of the Investigator 2. Has any progressive form of MS 3. Hypersensitivity to the active substance, or to any of the excipients of Lemtrada® 4. 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, to comply with the trial protocol, or to complete the study 5. Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS 6. 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 7. Known bleeding disorder (e.g,. dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand’s disease, disseminated intravascular coagulation (DIC), fibrinogen deficiency, or clotting factor deficiency) 8. 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 9. History of malignancy, except basal skin cell carcinoma 10. Major psychiatric disorder that is not adequately controlled by treatment 11. Epileptic seizures that are not adequately controlled by treatment 12. Active infection, e.g., deep-tissue infection, that the Investigator considers sufficiently serious to preclude study participation 13. In the Investigator’s opinion, is at high risk for infection (e.g., indwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration pneumonia or recurrent urinary tract infection) 14. Seropositivity for human immunodeficiency virus (HIV) 15. Infection with hepatitis C virus 16. Past or present hepatitis B infection (positive hepatitis B serology) 17. Active infection with human cytomegaly virus (HCMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) 18. Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis 19. Invasive fungal infections in history and at present 20. Cervical cytology other than PAP I or PAP II (Papanicolaou) or cervical high risk human papillomavirus (HPV) positivity 21. Any other illness or infection (latent or active) that, in the Investigator’s opinion, could be exacerbated by study medication 22. Differential blood count 1.5 × ULN SGOT/AST >3.0 × ULN SGPT/ALT >3.0 × ULN Alkaline phosphatase >2.5 × ULN Renal: Creatinine > 1.5 x ULN 26. Vaccinat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Combining clinical data with ex vivo and in vitro data, the study aims to shed more light on the mechanisms of action and the neuroprotective potential of alemtuzumab;Secondary Objective: Not appicable;Primary end point(s): Absolute and relative change from baseline of the following cell-counts in the peripheral blood: a. T cell subsets: - CD4 and CD8 positive T cells: naïve T cells, T effector cells, T memory cells, regulatory T cells; - T-helper subsets: Th1, Th2, Th17 b. B cell subsets: - Recent bone marrow emigrants, mature naïve, memory B cells - Plasma cells c. Natural killer cells: - CD56bright, CD56dim - Natural killer T cells d. Antigen-Presenting cells: - Dendritic cells: CD303+ plasmacytoid, CD11c+ and CD141+ myeloid dendritic cells - Monocytes and macrophages e. Myeloid-derived suppressor cells. ;Timepoint(s) of evaluation of this end point: 12, 24 and 36 months after initiaton of investigational treatment. In addition, on an optional basis: 6, 18 and 30 months after treatment initiation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Effficacy endpoints: 12, 24 and 36 months after initiation of investigational treatment. In addition, on an optional basis: 6, 18 and 30 months after treatment initiation, evaluation of certain non-invasive investigations even every 3 months. Examinations of CSF every 12 months only using samples collected on an optional basis. Safety endpoints: At least monthly monitoring for autoimmune diseases, at least quarterly monitoring for autoimmune thyroid diseases, at least semiannual performance of any other safety assessments.;Secondary end point(s): 1. Absolute and relative change from baseline in cell-counts in the CSF. The same cell-types as indicated for the primary endpoints will be evaluated. 2. Functional characterization of T-cells in the peripheral blood and the CSF: a. Activation status of cell surface receptors assessed by flow cytometry: Relative and absolute change from baseline of mean fluorescence intensity (MFI) and of proportion of positive cells regarding CD25, HLA-DR, LFA-1, CD29, CD69, CD71 expression b. Expression of co-inhibitory molecules assessed by flow cytometry: Relative and absolute change from baseline of MFI and of proportion of positive cells regarding PD-1 = CD279, ICOS = CD278, TIM-3, CTLA4 expression c. Effector functions of CD4 and CD8 positive T cells: - Relative and absolute change from baseline of the results of cell proliferation assays assessed as percentage of proliferated cells - Relative and absolute change from baseline of cytokine production measurement assessed as concentration - Relative and absolute change from baseline of cytolytic activity assessed by flow cytometry measurement of MFI and proportion of positive cells regarding Granzyme B, Perforin and CD107a expression - Relative and absolute change from baseline of intracellular calcium response assessed as concentration d. Migrational capacity: - Relative and absolute change from baseline MFI and proport | — |
Countries
Germany
Contacts
Public ContactKlinik für Allgemeine Neurologie
Universitätsklinikum Münster
Outcome results
None listed