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

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) 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, dimethylfumarate, teriflunomide, alemtuzumab) 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 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 15 years (inclusive)
• 4) EDSS 2.5 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