Trial document




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  DRKS00014289

Trial Description

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Title

Escalationtherapy of a MS-relapse by Methylprednisolone vs Immunoadsorption

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Trial Acronym

EMMA

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URL of the Trial

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Brief Summary in Lay Language

This study will include patients with an acute relapse of multiple sclerosis, who received a first course of high-dose methylprednisolone (or an equivalent therapy) and did not respond satisfactory to this treatment. Two therapies will be compared: 1) a second high-dose methylprednisolone intravenously over 5 days and 2) five sessions of immunadsorption – an extracorporeal blood purification. Patients consenting to study participation will be randomized into one of the study arms.
The aim of the study is to find out, if treatment with immunadsorption at this time point leads to a higher improvement of MS symptoms compared to a second treatment with high-dose methylprednisolone. Furthermore, the tolerability of immunadsorption will be investigated.

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Brief Summary in Scientific Language

Efficacy: Confirmatory analysis by ANCOVA with stratification criteria and EDSS pre values as covariates and treatment as factor.
Description of the primary efficacy analysis and population: within full analysis set of all randomised patients following the intention-to-treat principle; no interim analysis.
Safety: Frequencies of (S)AE/(S)AR/(S)ADE, other clinically relevant safety results by Fisher's exact test, if applicable.
Secondary endpoint(s): all courses of EDSS/MSFC/pFS and Snellen score analysed by repeated-measures ANCOVA; QoL, depression and fatigue changes, compliance to/acceptance of treatment analysed by Mann-Whitney-U-Test; proportions analysed by Fisher’s exact test; neither.

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Do you plan to share individual participant data with other researchers?

Yes

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Description IPD sharing plan:

Selected anonymous data will be made available to the companies supporting the study at the end of the study for further research purposes.
This is only patient data concerning the medical device of the respective company.
In addition, the companies receive a semi-annual status report on the current status of the studies (no patient data).

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Organizational Data

  •   DRKS00014289
  •   2018/06/18
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  •   yes
  •   Approved
  •   072/18-ff, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig
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Secondary IDs

  •   2017-000635-13 
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Health Condition or Problem studied

  •   Multiple sclerosis acute and progressive
  •   G35 -  Multiple sclerosis
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Interventions/Observational Groups

  •   Immunoadsorption (IA): a selective extracorporeal blood purification technique, performed in 5 sessions within 10 days
  •   Daily infusion of 2000 mg i.v. methylprednisolone for 5 days
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   assessor
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   No
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Primary Outcome

To prove the superiority of immunoadsorption over a 2nd course of methylprednisolone as an escalating treatment of steroid refractory relapses in RRMS (relapsing-remitting multiple sclerosis) and CIS (clinically isolated syndrom).

Primary efficacy endpoint: EDSS (Expanded Disability Status Scale) on day 45 or before start of any rescue treatment after EoT (end of tratment), (if applicable).

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Secondary Outcome

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).

Key secondary endpoints (sEP)
• subscore in the functional system predominantly affected by the current relapse (pFS)
• MSFC (MS Functional Composite)
• visual acuity (by Snellen score); in optic neuritis
• HRQoL measures (Health-Related Quality of Life)
Secondary Outcomes will be analysed on day 45 and at end of study.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2019/12/11
  •   140
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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 (Expanded Disability Status Scale)
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

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Exclusion Criteria

1. Primary (PPMS) or secondary progressive MS (SPMS)
2. Pseudo-relapse associated with fever or infection
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
• 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

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Addresses

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    • Universitätsklinikum Leipzig
    • Liebigstr. 18
    • 04103  Leipzig
    • Germany
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    • Universität Leipzig Medizinische Fakultät ZKS Leipzig - KKS
    • Ms.  Nicole  Köppe-Bauernfeind  
    • Härtelstr. 16-18
    • 04107  Leipzig
    • Germany
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    • Klinik und Poliklinik für Neurologie
    • Mr.  Prof. Dr. med.  Florian  Then Bergh 
    • Liebigstraße 20
    • 04103  Leipzig
    • Germany
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    • Klinik und Poliklinik für Neurologie
    • Mr.  Prof. Dr. med.  Florian  Then Bergh 
    • Liebigstraße 20
    • 04103  Leipzig
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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    • Miltenyi Biotec GmbH
    • Friedrich-Ebert-Straße 68
    • 51429  Bergisch Gladbach
    • Germany
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    • Fresenius Medical Care Deutschland GmbH
    • Else-Kröner-Strasse 1
    • 61352  Bad Homburg
    • Germany
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    • DIAMED Medizintechnik GmbH
    • Stadtwaldgürtel 77
    • 50935  Köln
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

  •   Prüfplan der EMMA Studie
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* This entry means the parameter is not applicable or has not been set.