Multiple Sclerosis (MS), acute episode MedDRA version: 20.0 Level: HLT Classification code 10052785 Term: Multiple sclerosis acute and progressive System Organ Class: 100000004852
Conditions
Interventions
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: Methylprednisolone
Other descriptive name: METHYLPREDNISOLONE
Concentration unit: mg milligram(s)
Concentration
Sponsors
Universität Leipzig
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. = 18 years 2. Diagnosis of MS (according to McDonald criteria, revision of 2017) or of clinically isolated syndrome of CNS demyelination 3. Acute relapse (new or recurring symptoms lasting at least 24 hrs, affecting the subject’s activities of daily living [ADL]) 4. Initial therapy of current relapse with IVMP (2500 - 5000 mg total dose) with unsatisfactory response 5. EDSS at screening 2.0-8.0 6. At screening, interval since onset of current relapse maximum 28 days 7. At screening, interval since end of initial course of IVMP** at least 7 days 8. Before onset of qualifying MS relapse, clinically stable for at least 30 days 9. Written informed consent 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 140 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Primary (PPMS) or secondary progressive MS (SPMS) 2. Pseudo-relapse associated with fever or infection. Assessment of a potential pseudo-relaose will be performed at screening and include a) history, b) clinical findings on physical examination, c) vital signs and d) laboratory results. 3. Known chronic autoimmune disorder (except for autoimmune thyroidits with hypothyroidism under sufficient substitution treatment) or deteriorating neurological condition except for MS 4. Known malignant disease within 5 years of screening (except for localized basal cell carcinoma) 5. Current or past relevant psychiatric disease (dementia, dissociative disorder, psychotic features, schizophrenia) 6. Current depression (if BDI > 17 pts., thorough clinical evaluation is necessary to determine if MP therapy is feasible) 7. Known allergies against methylprednisolone, a component of the MP product to be used locally; or against any components of immunoadsorption columns potentially used at the study site (i.e. camelid immunoglobulins or agarose if TheraSorb® may be used; protein A/ Peptid GAM if Immunosorba/Globaffin® may be used) 8. Side-effects from MP during the initial treatment course that would, if recurring, foreseeably lead to MP discontinuation 9. Contraindications to the use of methylprednisolone: • Insufficiently controlled diabetes • Insufficiently controlled arterial hypertension; • active infection with elevated inflammation parameters (e.g. hemogram, CrP); • tuberculosis (According to the Fachinformation (SmPC) for methylprednisolone, tuberculosis should be ruled out before any administration of i.v. methylprednisolone; unless a chest X-ray was performed and found unremarkable within the past year, a chest X-ray is recommended. Such chest X-ray constitutes part of clinical routine and is not a study procedure. ) • vaccination with a live vaccine within 2 weeks before randomization; • severe osteoporosis / osteopenia; 10. Contraindications to the use of IA: • Current use of ACE-inhibitors or sartans (taken within 3 d prior to visit 3/beginning of treatment), which can neither be replaced nor paused • Known disorders of the hemostatic system of vascular (e.g. von Willebrand syndrome), coagulation (e.g. hemophilia) or cellular (e.g. thrombocytopenia) origin • Conditions that prohibit anticoagulation using heparin and/or citrate 11. Abnormal results of coagulation tests, or thrombocytopenia at Screening acc. to local laboratory reference values 12. Known active infection with hepatitis B, C or HIV 13. Any condition which is, at the time of screening and foreseeably for the remaining study period, severely compromising immune function (e.g. AIDS, severe systemic infection) 14. Current drug abuse 15. Pregnant or breast feeding women 16. Women of child bearing potential without highly effective contraceptive measures (Clinical Trial Facilitation Group (CTFG) 9/15/2014) during the interval between screening and day 45. 17. Anticipated poor compliance (e.g. due to long travel distance to the trial site) 18. Current participation in other interventional clinical trial 19. Patients under legal supervision or guardianship. 20. Patients placed in an institution by official or court order
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prove the superiority of immunoadsorption over a 2nd course of methylprednisolone as an escalating treatment of steroid refractory relapses in RRMS and CIS. ;Secondary Objective: Validation of the superiority of immunoadsorption based on further neurological evaluations (e.g. MS functional composite/MSFC) and comparison of the two treatment modalities regarding safety and patient satisfaction (acceptance, well-being, quality of life).;Primary end point(s): Primary efficacy endpoint: EDSS on day 45 or before start of any rescue treatment after EoT (if applicable) ;Timepoint(s) of evaluation of this end point: On day 45 or before start of any rescue treatment after EoT (if applicable) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints (sEP) • subscore in the functional system predominantly affected by the current relapse (pFS) • MSFC • visual acuity (by Snellen score); in optic neuritis • HRQoL measures;Timepoint(s) of evaluation of this end point: On days 45, 90 and 180. | — |
Countries
Germany
Contacts
Public ContactKlinik und Poliklinik für Neurologi
Universität Leipzig
Outcome results
None listed