Autologous Mesenchymal Stromal Cells for Multiple Sclerosis

Study Overview
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Brief Summary
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This study evaluates the effect of cryopreserved autologous adult bone-marrow mesenchymal stromal cells (BM-MSC) in patients with active multiple sclerosis, compared to placebo. Patients will be allocated to one of the 2 treatment arms (BM-MSC or placebo)and at month 6, the treatment will be crossed to receive the other product. The objective is to assess the safety of a single infusion BM-MSC, and to explore its efficacy in these patients. Patients will be evaluated at month 12 and will be followed-up for a total of 3 years.

Detailed Description
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To date, there is no effective therapy to cure multiple sclerosis (MS). Immunomodulatory therapies are useful in reducing the frequency of inflammatory processes (relapses) but don't delay significantly the progression of the disease, prevent long term disability or induce the repair of damaged tissue. This proposal contemplates the use of adult autologous bone marrow mesenchymal stromal cells (BM-MSC) as an alternative therapeutic strategy to treat patients with active MS. This is a randomized, double blind, crossover clinical trial in which 8 patients with active forms of MS and moderate disability will enter the trial with the primary objective of assessing the safety and tolerability of a single intravenous infusion of BM-MSC. Secondary objectives are to assess the efficacy by gadolinium enhancing lesions though magnetic resonance imaging, neurophysiological effects and immunological effects. Once randomized, patients will undergo BM extraction and once confirmed the availability of the needed dose, they will be randomized to one of the 2 treatment arms (BM-MSC named XCEL-MC-ALPHA, or placebo). XCEL-MC-ALPHA will be cryopreserved for all patients regardless the allocated arm. At month 6, the treatment will be crossed. Patients will be evaluated at month 12 and will be followed-up for a total of 3 years.

Official Title
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Treatment of Autologous Mesenchymal Stem Cells Derived From Bone Marrow as a Potential Therapeutic Strategy for the Treatment of Multiple Sclerosis

Conditions
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Relapsing-Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis

Intervention / Treatment
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* Drug: XCEL-MC-ALPHA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18 and 60 years of age Patients with MS Relapsing-remitting or secondary progressive MS Patients to whom are not indicated or are not in a position to initiate treatment with disease-modifying drugs Expanded Disability Status Scale (EDDS) score <6.5 Nine T2 lesions at least Active multiple sclerosis as defined either by 1 outbreak in the last year or at least one Gadolinium-enhancing lesion in the last 6 months Signed informed consent form Exclusion Criteria: Interferon beta or glatiramer acetate 3 months prior the screening Natalizumab or fingolimod in the 6 months prior the screening Mitoxantrone, cyclophosphamide or other immunosuppressive therapy at any time Has received an experimental treatment within 3 months prior the screening MS outbreak within the 4 weeks prior the randomization Serum creatinine> 2.0 mg/dl Infectious disease active or uncontrolled Fertile patients who are not using a suitable method of contraception Pregnant or lactating woman Immunodeficiency Positive serology to HIV, Hepatitis B, Hepatitis C or syphilis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A: XCEL-MC-ALPHA/Placebo<br>Single infusion of cryopreserved bone-marrow adult mesenchymal stromal cells followed by placebo infusion at month 6. | Drug: XCEL-MC-ALPHA<br>* Single infusion<br>* Other names: Bone-marrow mesenchymal stromal cells;Drug: Placebo<br>* Single infusion<br>|
| Experimental: Treatment B: Placebo/XCEL-MC-ALPHA<br>Single infusion of placebo followed by cryopreserved bone-marrow adult mesenchymal stromal cells infusion at month 6. | Drug: XCEL-MC-ALPHA<br>* Single infusion<br>* Other names: Bone-marrow mesenchymal stromal cells;Drug: Placebo<br>* Single infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Safety profile | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative number of MRI Gd-enhancing lesions | Imaging procedure | 12 months | 
| Multiple Sclerosis Outbreaks | Medical assessment | 12 months | 
| Expanded Disability Status Scale (EDDS) score | Quantification of disability | 12 months | 
| Cumulative number of lesions visualized on T2 sequence | Imaging procedure | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, Bone marrow mesenchymal stromal cells, Stem cells, Nervous System Diseases, Demyelinating Diseases, Autoimmune Diseases