Mesenchymal Stem Cells for Multiple Sclerosis

NCT ID: NCT01730547

Last Updated: 2023-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2021-11-20

Brief Summary

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

Detailed 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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Early treatment with mesenchymal stem cells

Patients receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24. Fommow up at week 48

Group Type: ACTIVE_COMPARATOR

Autologous mesenchymal stem cells

Intervention Type: BIOLOGICAL

Delayed treatment with mesenchymal stem cells

Patients receive placebo for 24 weeks followed by autologous MSCs at week 24, with a follow-up visit at week 48.

Group Type: ACTIVE_COMPARATOR

Autologous mesenchymal stem cells

Intervention Type: BIOLOGICAL

Interventions

Autologous mesenchymal stem cells

Intervention Type: BIOLOGICAL

Eligibility 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 (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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Lou Brundin

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Karolinska Institute, Karolinska University Hospital Solna

Stockholm, , Sweden

Countries

Sweden

References

Uccelli A, Laroni A, Brundin L, Clanet M, Fernandez O, Nabavi SM, Muraro PA, Oliveri RS, Radue EW, Sellner J, Soelberg Sorensen P, Sormani MP, Wuerfel JT, Battaglia MA, Freedman MS; MESEMS study group. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis. Trials. 2019 May 9;20(1):263. doi: 10.1186/s13063-019-3346-z.

Reference Type: DERIVED

PMID: 31072380 (View on PubMed)

Other Identifiers

MSC-MS

Identifier Type: -

Identifier Source: org_study_id