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

NCT02239393 | Completed Phase 2 DMC

• 1 other identifier: 20140368
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Mesenchymal Stem Cells; MSC

Outcome Measures

Primary Outcomes (2)

• Safety

  Incidence and severity of adverse events in MSC treatment group compared to placebo group

  24 weeks from first infusion

• Efficacy

  Total number of gadolinium-enhancing lesions (GEL) on MRI scan

  24 weeks from first infusion

Secondary Outcomes (5)

• Efficacy

  48 weeks from first infusion

• Efficacy

  24 weeks from first infusion

• Efficacy

  48 weeks from first infusion

• Efficacy

  48 weeks from first infusion

• Efficacy

  48 weeks from first infusion

Study Arms (2)

Autologous Mesenchymal Stem Cells

EXPERIMENTAL

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

Suspension media

EXPERIMENTAL

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

Interventions

Mesenchymal Stem Cells BIOLOGICAL

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).

Autologous Mesenchymal Stem Cells; Suspension media

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \) Males and females with a diagnosis of MS
• 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
• 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
• 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)
• \) Age 18 to 50 years old, inclusive at time of informed consent
• \) Disease duration 2 to 15 years (inclusive)
• \) EDSS 2.5 to 6.5

You may not qualify if:

• \) A history of active or chronic infection including infection with HIV1-2, chronic Hepatitis B or Hepatitis C
• \) Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
• \) Previous treatment with cladribine or alemtuzumab
• \) 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)
• \) Treatment with corticosteroids within the 30 days prior to randomization
• \) Relapse occurred during the 60 days prior to randomization
• \) 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
• \) Severely limited life expectancy by any other co-morbid illness
• \) History of previous diagnosis of myelodysplasia or previous hematologic disease (patient reported) or current clinically relevant abnormalities of white blood cell counts
• \) Pregnancy or risk of pregnancy (this includes participants that are not willing to practice active contraception for the duration of the study)
• \) eGFR \< 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination
• \) Known allergy to gentamicin or related aminoglycosides
• \) Inability to give written informed consent in accordance with research ethics board guidelines
• \) Concomitant participation in another clinical trial
• \) Inability to adhere to protocol according to the investigator's medical judgement

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (2)

Health Sciences Centre

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (2)

• Thebault S, Reaume M, Marrie RA, Marriott JJ, Furlan R, Laroni A, Booth RA, Uccelli A, Freedman MS. High or increasing serum NfL is predictive of impending multiple sclerosis relapses. Mult Scler Relat Disord. 2022 Mar;59:103535. doi: 10.1016/j.msard.2022.103535. Epub 2022 Jan 19.

  PMID: 35078125 DERIVED

• 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.

  PMID: 31072380 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Mark S. Freedman, MSc MD FRCPC

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2014
• First Posted: September 12, 2014
• Study Start: June 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: March 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)