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Safety and Efficacy of Intravenous Autologous Mesenchymal Stem Cells for MS: a Phase 2 Proof of Concept Study (MESCAMS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Ottawa Hospital Research Institute
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT02239393
First received: September 10, 2014
Last updated: January 6, 2016
Last verified: January 2016
  Purpose

The mechanism of action of MSC relies on their ability to modulate pathogenic immune responses and provide neuroprotection through the release of anti-apoptotic, anti-oxidant and trophic factors as demonstrated by in-vitro and in-vivo preclinical studies.

Patients will be randomized to receive immediate vs. delayed treatment with either a dose equal to 1-2 millions/kg of body weight of autologous MSC, or equivalent volume of suspension media at baseline. At week 24 treatments will be reversed.

The primary outcome of this study is to evaluate:

  • Treatment's safety within one year from MSC administration by measuring the number, time-frame and severity of adverse events and
  • Treatment's activity in terms of reduction in total number of gadolinium-enhancing lesions (GEL) by magnetic resonance imaging (MRI) scans.

Secondary outcomes are to gain preliminary information on the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).


Condition Intervention Phase
Multiple Sclerosis
Biological: Mesenchymal Stem Cells
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: MEsenchymal Stem Cell Therapy for CAnadian MS Patients

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Safety [ Time Frame: 24 weeks from first infusion ] [ Designated as safety issue: Yes ]
    Incidence and severity of adverse events in MSC treatment group compared to placebo group

  • Efficacy [ Time Frame: 24 weeks from first infusion ] [ Designated as safety issue: No ]
    Total number of gadolinium-enhancing lesions (GEL) on MRI scan


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 48 weeks from first infusion ] [ Designated as safety issue: No ]
    Number of gadolinium-enhancing lesions (GEL) counted over week 28, 36, 48 compared with the number of GEL counted over 4, 12, 24 weeks.

  • Efficacy [ Time Frame: 24 weeks from first infusion ] [ Designated as safety issue: No ]
    Combined unique magnetic resonance imaging (MRI) activity (number of new or enlarging T2, or enhancing or re-enhancing lesions), volume of gadolinium-enhancing lesions (GEL) and volume of black holes (BH) over 4, 12, 24 weeks compared between treatment groups.

  • Efficacy [ Time Frame: 48 weeks from first infusion ] [ Designated as safety issue: No ]
    Combined unique magnetic resonance imaging (MRI) activity, volume of gadolinium-enhancing lesions (GEL) and volume of black holes (BH) over week 28, 36, 48 compared with the same outcomes over 4, 12 and 24 weeks.

  • Efficacy [ Time Frame: 48 weeks from first infusion ] [ Designated as safety issue: No ]
    Number of relapses in MSC treatment group vs. placebo group in the first 24 weeks and after cross-over re-treatment in the two groups.

  • Efficacy [ Time Frame: 48 weeks from first infusion ] [ Designated as safety issue: No ]
    Time to sustained progression of disability and proportion of progression-free patients compared between treatment groups during the first 24 weeks and after cross-over.


Estimated Enrollment: 40
Study Start Date: June 2015
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Autologous Mesenchymal Stem Cells
At week 0 a single infusion of either ex-vivo expanded autologous MSC or suspension media will be administered intravenously at a dose of 1 to 2 x 1000000 MSC/Kg body weight. At week 24, another infusion will be performed for cross-over re-treatment: at week 24 treatments will be reversed compared to week 0.
Biological: Mesenchymal Stem Cells

Mesenchymal Stem Cells in Plasma-Lyte A (Baxter) suspension media, containing 5% Human Albumin and 10% dimethylsulfoxide (DMSO, total volume of 5mL DMSO in final cell product) and autologous MSCs at a dose of 1 to 2 x 106 MSC/Kg participant's body weight at randomization.

Matching placebo Plasma-Lyte A (Baxter) suspension media, containing 5% Human Albumin and 10% DMSO (total volume of 5mL DMSO in final cell product).

Experimental: Suspension media
At week 0 a single infusion of either ex-vivo expanded autologous MSC or suspension media will be administered intravenously at a dose of 1 to 2 x 1000000 MSC/Kg body weight. At week 24, another infusion will be performed for cross-over re-treatment: at week 24 treatments will be reversed compared to week 0.
Biological: Mesenchymal Stem Cells

Mesenchymal Stem Cells in Plasma-Lyte A (Baxter) suspension media, containing 5% Human Albumin and 10% dimethylsulfoxide (DMSO, total volume of 5mL DMSO in final cell product) and autologous MSCs at a dose of 1 to 2 x 106 MSC/Kg participant's body weight at randomization.

Matching placebo Plasma-Lyte A (Baxter) suspension media, containing 5% Human Albumin and 10% DMSO (total volume of 5mL DMSO in final cell product).


Detailed Description:

The mechanism of action of Mesenchymal Stem Cells (MSCs) relies on their ability to modulate pathogenic immune responses and provide neuroprotection through the release of anti-apoptotic, anti-oxidant and trophic factors as demonstrated by in vitro and in vivo preclinical studies.

Patients will be randomized to receive immediate vs. delayed treatment with either a dose equal to 1-2 millions/kg of body weight of autologous MSC, or equivalent volume of suspension media at baseline. At 6 months treatments will be reversed.

The primary outcome of this study is to evaluate

  • treatment's safety within one year from MSC administration by measuring the the number, time-frame and severity of adverse event and
  • treatment's activity in terms of reduction in the total number of contrast-gadolinium enhancing lesions (GEL) by magnetic resonance imaging (MRI) scans.

Secondary outcomes are to gain preliminary information on the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1) Males and females with a diagnosis of MS

    1. Relapsing remitting MS (RRMS) not responding to at least 1 year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, dimethyl fumarate, teriflunomide, alemtuzumab) as evidenced by at least one of the following:

      • i) ≥1 clinically documented relapse in past 12 months
      • ii) ≥2 clinically documented relapses in past 24 months
      • iii) ≥1 gadolinium-enhancing lesion (GEL) at MRI performed within the past 12 months
    2. Secondary progressive MS (SPMS) with 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 past 12 months
      • ii) ≥1 clinically documented relapse or ≥ 1 gadolinium-enhancing lesion (GEL) at MRI within the past 12 months
    3. 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 past 12 months
      • ii) ≥ 1 gadolinium-enhancing lesion (GEL) at MRI performed within the past 12 months
      • iii) positive cerebrospinal fluid (CSF) (oligoclonal banding)
  • 2) Age 18 to 50 years old, inclusive at time of informed consent
  • 3) Disease duration 2 to 10 years (inclusive)
  • 4) EDSS 3.0 to 6.5
  • 5) Able and willing to sign informed consent prior to any study-related activities

Exclusion Criteria:

  • 1) RRMS not fulfilling inclusion criteria
  • 2) SPMS not fulfilling inclusion criteria
  • 3) PPMS not fulfilling inclusion criteria
  • 4) A history of active or chronic infection including infection with HIV1-2, chronic Hepatitis B or Hepatitis C
  • 5) Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
  • 6) Previous treatment with cladribine or alemtuzumab
  • 7) Treatment with interferon-beta, glatiramer acetate, teriflunomide or dimethyl fumarate within the 30 days prior to randomization (all teriflunomide patients will be required to have followed a wash-out with either cholestyramine or activated charcoal as indicated in the product monograph)
  • 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 a malignancy (patient reported) other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year
  • 11) Severely limited life expectancy by any other co-morbid illness
  • 12) History of previous diagnosis of myelodysplasia or previous hematologic disease (patient reported) or current clinically relevant abnormalities of white blood cell counts
  • 13) Pregnancy or risk of pregnancy (this includes participants that are not willing to practice active contraception for the duration of the study)
  • 14) eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination
  • 15) Known allergy to gentamicin or related aminoglycosides
  • 16) Inability to give written informed consent in accordance with research ethics board guidelines
  • 17) Concomitant participation in another clinical trial
  • 18) Inability to adhere to protocol according to the investigator's medical judgement
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02239393

Contacts
Contact: Carol Freedman, BMR (PT) MESCAMS@ohri.ca

Locations
Canada, Manitoba
Health Sciences Centre Recruiting
Winnipeg, Manitoba, Canada, R3A 1R9
Contact: James J. Marriott, MD MSc FRCPC    204-787-4951    jmarriott@exchange.hsc.mb.ca   
Contact: Barbara Stanger, RN    204-787-2905    bstanger@hsc.mb.ca   
Principal Investigator: James J. Marriott, MD MSc FRCPC         
Canada, Ontario
Ottawa Hospital - General Campus Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Catherine Hilliker, RN    613-737-8104 ext 7    MESCAMS@ohri.ca   
Principal Investigator: Mark S. Freedman, MD MSc FRCPC         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
Principal Investigator: Mark S. Freedman, MSc MD FRCPC Ottawa Hospital Research Institute
  More Information

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT02239393     History of Changes
Other Study ID Numbers: 20140368 
Study First Received: September 10, 2014
Last Updated: January 6, 2016
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
Multiple Sclerosis
Mesenchymal Stem Cells
MSC

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 23, 2016