MEsenchymal StEm Cells for Multiple Sclerosis

NCT02403947 | Terminated Phase 1 DMC

• 1 other identifier: 12 394 03
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), which ultimately leads to myelin damage and axonal loss. The disease is complex and multifactorial, but the key pathogenic event appears to be an uncontrolled response of components of the immune system (T and B lymphocytes) to myelin proteins. No definitive treatment is available for MS, however immunomodulatory and immunosuppressant drugs act as disease-modifying agents (DMDs). Unfortunately, the current treatments demonstrate partial efficacy in targeting the deleterious immune reactions. According to the present knowledge of the pathophysiology of MS, an ideal therapeutic strategy would be to modulate or suppress the aggressive immune process, to protect axons and neurons from degeneration, and to enhance repair and facilitate remyelination. A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown remarkable ability to modulate the immune response. This study will evaluate the safety of injecting MSCs in people with MS.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Bone-marrow; Stem cells; Cell therapy

Outcome Measures

Primary Outcomes (2)

• Safety of MSCs infusion, number, timeframe of occurrence and severity of Adverse Events

  Safety assessed by number, timeframe of occurrence and severity of Adverse Events

  24 weeks from the first infusion

• efficacy: number of contrast-enhancing lesions (GEL) at MRI scan

  total number of contrast-enhancing lesions (GEL) at MRI scan

  24 weeks from the first infusion

Secondary Outcomes (5)

• Efficacy of the experimental treatment in term of combined MRI activity

  48 weeks from the first infusion

• Efficacy assessed by combined unique MRI activity, volume of GEL, and volume of BH

  24 weeks from the first infusion

• Efficacy assessed by combined unique MRI activity, volume of GEL and volume of BH

  48 weeks from the first infusion

• Efficacy: Number of relapses

  24 weeks from the first infusion

• Efficacy: Time to sustained progression of disability

  24 weeks from the first infusion

Study Arms (2)

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 1-2 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

Drug: Mesenchymal stem cells

Suspension media

PLACEBO COMPARATOR

At week 0 a single infusion of either ex-vivo expanded autologous MSC or suspension media will be administered intravenously at a dose of 1-2 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

Drug: Suspension media

Interventions

Mesenchymal stem cells DRUG

After the sampling of bone-marrow and culture of MSCs by the French Blood Establishment (Midi-Pyrénées), patients will receive an IV injection of MSCs.

Mesenchymal stem cells

Suspension media DRUG

injection suspension media

Suspension media

Eligibility Criteria

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

You may qualify if:

• Age 18 to 50 years
• Disease duration 2 to 10 years (included)
• Diagnosis of MS
• 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:
• more or egal 1 clinically documented relapse in past 12 months
• more or egal 2 clinically documented relapses in last 24 months
• more or egal 1 GEL at MRI performed within the last 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) as evidenced by both::
• With more or egal 1 clinically documented relapse in the last twelve months
• Without on-going relapses, but with more or egal 1 GEL at MRI performed within the last 12 months.
• Primary progressive MS (PPMS) patients with all the following features:
• more or egal 1 GEL at MRI performed within the last 12 months
• Positive cerebrospinal fluid (CSF) (oligoclonal banding).
• EDSS (Expanded Disability Status Scale) 3.0 to 6.5
• Women of childbearing age with an effective contraception.

You may not qualify if:

• Inferior to 3 months since treatment with any immunosuppressive therapy including natalizumab and fingolimod
• Inferior or egal to 1 month since last treatment with interferon-beta or glatiramer acetate
• Corticosteroid treatment Inferior or egal to 30 days
• Relapse inferior or egal to 60 days
• Any active or chronic infection including infection with HIV1-2 (Human Immunodeficiency Virus 2) or HTLV I-II (Human T-lymphotropic virus I-II) or Syphilis or chronic Hepatitis B or Hepatitis C inferior to 1 month
• 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 (estimated Glomerular Filtration Rate ) inferior to 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.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Purpan Hospital

Toulouse, 31059, France

Location

Related Publications (1)

• 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

• Clanet Michel, MD,PhD

  Neurology Department of Purpan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: March 9, 2015
• First Posted: March 31, 2015
• Study Start: February 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: December 3, 2018

Record last verified: 2018-11

Locations

FR (1)