Mesenchymal Stem Cells for Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Phase 1/2 Clinical Trial With Autologous Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01730547
• Other study ID #: MSC-MS
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2013
• Est. completion date: November 20, 2021

Study information

• Verified date: May 2023
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to evaluate the safety and efficacy of autologous mesenchymal stromal cells as treatment for Multiple Sclerosis.

Description:

MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18-50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2-15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5-6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: November 20, 2021
• Est. primary completion date: May 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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 (beta-interferon, glatiramer acetate, 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

b. Secondary progressive MS (SPMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by both: i. an increase of =1 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 the following features: i. an increase of =1 EDSS point (if at randomization EDSS = 5.0) or 0.5 EDSS point (if at randomization EDSS =5.5), in the last twelve 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

Exclusion Criteria:

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 Hepatitis C

5. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization

6. Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization

7. Treatment with corticosteroids within the 30 days prior to randomization

8. Relapse occurred during the 60 days prior to randomization

9. Previous history of a malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year

10. Severely limited life expectancy by another co-morbid illness

11. History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts

12. Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study)

13. eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination.

14. Inability to give written informed consent in accordance with research ethics board guidelines

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• Autologous mesenchymal stem cells

Locations

Country	Name	City	State
Sweden	Karolinska Institute, Karolinska University Hospital Solna	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the safety of IV therapy with autologous Mesenchymal Stem Cells (MSCs) in MS patients.	The primary objective of the study is to assess the safety of IV therapy with autologous MSCs in MS. Number of participants with adverse events will be documented at week 0,4,8,12,16,20,24,28,32,36,40,44,48 post treatment. Co-primary objective of the study is to evaluate the activity of autologous MSCS in MS patients, in terms of reduction as compared to placebo in the total number of contrast-enhancing lesions (GEL) at MRI acquired on conventional 1,5 T MRI scans over 24 weeks.	48 weeks
Secondary	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).		48 weeks