Multiple Sclerosis MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: MAVENCLAD 10 mg tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: CLADRIBINE
CAS Number: 4291-63-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Westfälische Wilhelms-Universität Münster c/o Universitätsklinikum Münster, Geschäftsbereich Recht u. Drittmittel
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form (ICF) 2. Age 18 to 60 years old (inclusive) as of the date the ICF is signed 3. Diagnosis of MS according to the McDonald criteria 2017 and cranial MRI scan demonstrating white matter lesions attributable to MS 4. Therapy with cladribine is indicated (according to label) 5. EDSS score 0.0 to 6.0 (inclusive) 6. Patient did not receive cladribine treatment before and is cladribine treatment naive at time point of inclusion and first blood draw 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 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hypersensitivity to the active substance or to any of the excipients of the study medication 2. Acute infection 3. Infection with human immunodeficiency virus (HIV) 4. Active chronic infection (tuberculosis or hepatitis) 5. Suspected progressive multifocal leukoencephalopathy (PML) (a baseline magnetic resonance imaging (MRI) should be performed within 3 months before start of treatment with cladribine) 6. Varicella zoster virus antibody-negative patients 7. Immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy 8. Patients with significant disposition for infections 9. Abnormal lymphocyte count 10. Vaccination with live or attenuated live vaccines within 4 to 6 weeks before start of treatment with cladribine and also during and after cladribine treatment until normalization of white blood cell counts 11. Moderate or severe renal impairment (creatinine clearance 6) 13. Patients with active malignancies 14. Patients with hereditary problems of fructose intolerance 15. Pregnancy and breast-feeding 16. For female and male patients of reproductive potential: Unwilling to agree to use a highly effective method of contraception (Pearl index <1) within a period of 6 month after the last cladribine treatment. 17. Medical, psychiatric, cognitive, or other condition 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 18. Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial resp. 5 half-lives of the previously applied investigational medicinal product depending on which period is longer. Simultaneous inclusion of patients in the clinical trial MAGNIFY (EudraCT-No. 2017-002631-42, Sponsor: Merck KgaA) is permitted. There may be other exceptions at the discretion of the (coordinating) investigator. 19. Therapy with teriflunomide, ozanimod, ponesimod or fingolimod within 4 weeks before start of treatment with cladribine 20. Therapy with natalizumab within 6 weeks before start of treatment with cladribine 21. Therapy with mitoxantron, azathioprin, methotrexat, ciclosporin A or cyclophosphamid within 3 months before start of treatment with cladribine 22. Therapy with alemtuzumab, rituximab or ocrelizumab within 6 months before start of treatment with cladribine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Analysis of the T cell receptor repertoire of CD4 and CD8 T cells, and the B cell receptor repertoire of CD19 B cells before and during the first year after onset of cladribine treatment initiation. ;Secondary Objective: - Analysis of the T cell receptor repertoire of CD4 and CD8 T cells, and the B cell receptor repertoire of CD19 B cells before and during the second year after onset of cladribine treatment Initiation - Analysis of the impact of cladribine treatment on the transcriptional profile of CD4, CD8 and CD19 cells using unbiased RNAseq of sorted cells and PBMCs - Analysis of the impact of cladribine treatment on immune cell subsets (T cells, B cells, monocytes, NK cells, dendritic cells, CD4, CD8 T cells) - Analysis of the impact of cladribine treatment on immune cell activation status, markers of cell death and immune senescence - Analysis of the impact of cladribine treatment on mitochondrial energy metabolism (i.e. oxidative phosphorylation) of CD4 and CD8 T cells ;Primary end point(s): Changes in the T cell receptor repertoire (CD4 and CD8 T cells) and B cell receptor repertoire (CD19 B cells) 3 and 12 months after start of first treatment course (as compared to baseline) will be assessed using thawed PBMC by deep sequencing of the T cell receptor and the B cell receptor repertoire.;Timepoint(s) of evaluation of this end point: 3 and 12 months after start of first treatment course | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Changes in the T cell receptor repertoire (CD4 and CD8 T cells) and B cell receptor repertoire (CD19 B cells) 12 months after start of second treatment course (as compared to baseline) will be assessed using thawed PBMC by deep sequencing of the T cell receptor and the B cell receptor repertoire. • Changes in the transcriptional profiles of CD4 and CD8 T cells as well as CD19 B cells 3 and 12 months after start of first treatment course (as compared to baseline) will be assessed by RNAseq of sorted CD4, CD8, and CD19 expressing cells and PBMCs in a subgroup of 10 patients. • Changes in proportions and absolute counts of immune cell subsets (T cells, B cells, monocytes, NK cells, dendritic cells, CD4, CD8 T cells) 3 and 12 months after start of first treatment course (as compared to baseline), and 12 months after start of second treatment course (as compared to baseline), analyzed by flow cytometry. • Changes in the immune cell activation status, in markers of cell death and immune senescence 3 and 12 months after start of first treatment course (as compared to baseline), and 12 months after start of second treatment course (as compared to baseline), analyzed by flow cytometry. • Changes in the mitochondrial energy metabolism (i.e. oxidative phosphorylation) of CD4 and CD8 T cells, 3 and 12 months after start of first treatment course (as compared to baseline), and 12 months after start of second treatment course (as compared to baseline), assessed by maximal respiratory capacity using seahorse agilent technology (oxygen consumption rate in pmol/min). ;Timepoint(s) of evaluation of this end point: see above | — |
Countries
Germany
Contacts
Public ContactProf. Dr. med. Luisa Klotz
Klinik für Neurologie mit Institut für translationale Neurologie am UKM
Outcome results
None listed