Autologous Mesenchymal Stromal Cells for Multiple Sclerosis (EMMES)

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

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.

Study Overview

• Status: Completed
• Conditions: Relapsing-Remitting Multiple Sclerosis; Secondary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: XCEL-MC-ALPHA; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08005
    • Hospital Vall Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A: XCEL-MC-ALPHA/Placebo; Single infusion of cryopreserved bone-marrow adult mesenchymal stromal cells followed by placebo infusion at month 6.	Drug: XCEL-MC-ALPHA; Single infusion; Other Names: Bone-marrow mesenchymal stromal cells; Drug: Placebo; Single infusion
EXPERIMENTAL: Treatment B: Placebo/XCEL-MC-ALPHA; Single infusion of placebo followed by cryopreserved bone-marrow adult mesenchymal stromal cells infusion at month 6.	Drug: XCEL-MC-ALPHA; Single infusion; Other Names: Bone-marrow mesenchymal stromal cells; Drug: Placebo; Single infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Banc de Sang i Teixits
• Collaborators: Vall d'Hebron Research Institute (VHIR)
• Investigators: Principal Investigator: Xavier Montalban, MD, PhD, Hospital Vall d'Hebron

Publications and helpful links

Helpful Links

• Blood and Tissue Bank of Catalonia
• Multiple Sclerosis center of Catalonia
• Vall d'Hebron Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 11, 2015
• Primary Completion (ACTUAL): November 27, 2017
• Study Completion (ACTUAL): November 15, 2018

Study Registration Dates

• First Submitted: June 3, 2015
• First Submitted That Met QC Criteria: July 8, 2015
• First Posted (ESTIMATE): July 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 21, 2020
• Last Update Submitted That Met QC Criteria: January 15, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Stem cells; Multiple sclerosis; Nervous System Diseases; Autoimmune Diseases; Demyelinating Diseases; Bone marrow mesenchymal stromal cells
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: XCEL-MS-02