multiple sclerosis
Conditions
Interventions
Product Name: Human autologous mesenchymal stem cells
Pharmaceutical Form: Infusion
INN or Proposed INN: MSC2015
Other descriptive name: UNDIFFERENTIATED AUTOLOGOUS MESENCHYMAL STEM CELLS
Concentratio
Sponsors
SALK - Gemeinnützige Salzburger Landeskliniken Betriebsges. m.b.H., Christian-Doppler-Klinik, UK für Neurologie der PMU
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of MS a. Relapsing remitting MS (RRMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (Betainterferon, Glatirameracetate, Natalizumab, Mitoxantrone, Fingolimod) as evidenced by one or more of the following: i. =1 clinically documented relapse in past 12 months ii. =2 clinically documented relapses in last 24 months iii. =1 GEL at MRI performed within the last 12 months or new T2 lesion at MRI performed within the last 12 months compared to a previous MRI performed within the last 12 months. b. Secondary progressive MS (SPMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (betainterferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by both: i. an increase of =1.0 EDSS point (if at randomization EDSS = 5.0) or 0.5 EDSS point (if at randomization EDSS = 5.5) in the last 12 months ii. =1 clinically documented relapse or = 1 GEL at MRI within the last twelve months. c. Primary progressive MS (PPMS) patients with all following features: i. an increase of =1.0 EDSS point (if at randomization EDSS = 5.0) or 0.5 EDSS point (if at randomization EDSS =5.5), in the last 12 months ii. = 1 GEL at MRI performed within the last 12 months iii. positive cerebrospinal fluid (CSF), oligoclonal banding 2. Age 18 to 50 years 3. Disease duration 2 to 10 years (included) 4. EDSS 3.0 to 6.5 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 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: These criteria are used to exclude MS patients with medical problems that would significantly increase their risk of serious morbidity or mortality from MSCT or any other facet of this protocol: 1. RRMS not fulfilling inclusion criteria 2. SPMS not fulfilling inclusion criteria 3. PPMS not fulfilling inclusion criteria 4. Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or C, syphilis 5. Any chronic or acute disease or Known allergy to any substances related to study treatment that could be non compatible with the trial protocol as per clinician’s judgement 6. Treatment with any immunosuppressive therapy, including Natalizumab and Fingolimod, within the 3 months prior to randomization 7. Treatment with Interferon-beta or glatiramer acetate within the 30 days prior to randomization 8. Treatment with corticosteroids within the 30 days prior to randomization 9. Relapse occurred during the 60 days prior to randomization 10. Previous history of malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than 1 year 11. Severely limited life expectancy by another co-morbid illness 12. History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts 13. Pregnancy or risk of pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study) 14. eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination. 15. Inability to give written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to assess the safety of IV therapy with autologous MSCs in multiple sclerosis patients;Secondary Objective: to gather preliminary information of the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).;Primary end point(s): incidence and severity of adverse events in MSCs treatment group compared to placebo group Co-primary endpoint: number of GEL counted over week 4, 12 and 24 compared between treatment groups;Timepoint(s) of evaluation of this end point: 24 weeks after MSCs treatment or placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - number of GEL counted over week 28, 36 and 48 (cross-over re-treatment) compared with the number of GEL counted over 4, 12 and 24 weeks (placebo vs. active treatment periods) within each group - combined unique MRI activity (number of new or enlarging T2, or enhancing or reenhancing lesions), and volume of GEL over 4, 12, 24 weeks compared between treatment groups Volume of black holes (BH) over 24 weeks compared between treatment groups - combined unique MRI activity and volume of GEL over week 28, 36 and 48 (crossover re-treatment) compared with the same outcomes over 4, 12 and 24 weeks (placebo vs. active treatment periods) within each group. Volume of BH over week 48 (cross-over re-treatment) compared with the same outcome over week 24 week (placebo vs. active treatment periods) within each group - Volume of T2 lesions over 24 weeks compared between treatment groups - Volume of T2 lesions over week 48 (cross-over re-treatment) compared with the same outcome over week 24 week (placebo vs. active treatment periods) within each group - number of relapses in MSCs treatment group vs. placebo group in the first 24 weeks and after cross-over re-treatment in the two groups - time to sustained progression of disability and proportion of progression-free patients compared betweentreatment groups during the first 24 weeks and after cross-over re-treatment in the two groups - proportion of disease-free patients defined as patients without relapses, with no evidence of sustained progression of disability and new MRI activity compared between treatment groups during the first 24 weeks and after cross-over retreatment in the two groups - changes in Multiple Sclerosis Functional Composite (MSFC) score and Symbol Digit Modalities Test (SDMT) score in the MSC treated group vs. placebo group during the first 24 weeks and after cross-over re-treatment in the two groups;Timepoint(s) of evaluation of this end point: as described above in section E.5 | — |
Countries
Austria
Contacts
Public ContactDaniela Sinadinoska
SALK - Christian-Doppler-Klinik, Universitätsklinik für Neurologie der PMU, Studienbüro Neurologie
Outcome results
None listed