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Mesenchymal Stem Cells for Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status

Completed

Phase

Phase 1

Locations

Sweden

Study Type

Interventional

Intervention

Autologous mesenchymal stem cells

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Mesenchymal stem cells, Multiple Sclerosis, Autoimmune diseases

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
Age 18 to 50 years
Disease duration 2 to 10 years (included)
EDSS 3.0 to 6.5

Exclusion Criteria:

RRMS not fulfilling inclusion criteria
SPMS not fulfilling inclusion criteria
PPMS not fulfilling inclusion criteria
Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or Hepatitis C
Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization
Treatment with corticosteroids within the 30 days prior to randomization
Relapse occurred during the 60 days prior to randomization
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
Severely limited life expectancy by another co-morbid illness
History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts
Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study)
eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination.
Inability to give written informed consent in accordance with research ethics board guidelines

Sites / Locations

Karolinska Institute, Karolinska University Hospital Solna

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Early treatment with mesenchymal stem cells

Delayed treatment with mesenchymal stem cells

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

Full Information

NCT ID

NCT01730547

First Posted

November 9, 2012

Last Updated

May 30, 2023

Sponsor

Karolinska Institutet

1. Study Identification

Unique Protocol Identification Number

NCT01730547

Brief Title

Mesenchymal Stem Cells for Multiple Sclerosis

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

February 2013 (undefined)

Primary Completion Date

May 9, 2019 (Actual)

Study Completion Date

November 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Karolinska Institutet

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

Mesenchymal stem cells, Multiple Sclerosis, Autoimmune diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Early treatment with mesenchymal stem cells

Arm Type

Active Comparator

Arm Description

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

Arm Title

Delayed treatment with mesenchymal stem cells

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Autologous mesenchymal stem cells

Primary Outcome Measure Information:

Title

To assess the safety of IV therapy with autologous Mesenchymal Stem Cells (MSCs) in MS patients.

Description

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

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).

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Age 18 to 50 years Disease duration 2 to 10 years (included) EDSS 3.0 to 6.5 Exclusion Criteria: RRMS not fulfilling inclusion criteria SPMS not fulfilling inclusion criteria PPMS not fulfilling inclusion criteria Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or Hepatitis C Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization Treatment with corticosteroids within the 30 days prior to randomization Relapse occurred during the 60 days prior to randomization 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 Severely limited life expectancy by another co-morbid illness History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study) eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination. Inability to give written informed consent in accordance with research ethics board guidelines

Facility Information:

Facility Name

Karolinska Institute, Karolinska University Hospital Solna

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

31072380

Citation

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.

Results Reference

derived

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Mesenchymal Stem Cells for Multiple Sclerosis

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