MEsenchymal StEm Cells for Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— MESEMS  

Official title:

MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS) Phase I-II Clinical Trial With Autologous Mesenchymal Stem Cells (MSCs) for the Therapy of Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01854957
• Other study ID #: MESEMS
• Secondary ID: 2011-001295-19
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: May 8, 2013
• Last updated: May 13, 2013
• Start date: July 2012
• Est. completion date: September 2014

Study information

• Verified date: May 2013
• Source: University of Genova
• Contact: Antonio Uccelli, MD
• Phone: +390103537028
• Email: MESEMS[@]unige.it
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial Summary

A double-blind, randomized, cross-over phase I/II study to evaluate the safety and the efficacy of the intravenous administration of autologous Mesenchymal Stem Cells (MSC) to patients with active multiple sclerosis (MS) resistant to currently available therapies.

Description:

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 6 months 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 the number, time-frame and severity of adverse event and

• treatment's activity in terms of reduction in the total number of contrast-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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 1. Diagnosis of MS

a. 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: i. =1 clinically documented relapse in past 12 months

ii. =2 clinically documented relapses in last 24 months

iii. =1 GEL at MRI performed within the last 12 months

b. 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:

i. an increase of =1 point of the expanded disability status scale (EDSS) (if at randomization EDSS = 5.0) or 0.5 EDSS point (if at randomization EDSS = 5.5) in the last 12 months

ii. =1 clinically documented relapse or = 1 GEL at MRI within the last twelve months.

c. 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 last twelve months

ii. = 1 GEL at MRI performed within the last 12 months

iii. positive cerebrospinal fluid (CSF) (oligoclonal banding

• 2. Age 18 to 50 years

• 3. Disease duration 2 to 10 years (included)

• 4. EDSS 3.0 to 6.5

Exclusion Criteria:

• 1. RRMS not fulfilling inclusion criteria

• 2. SPMS not fulfilling inclusion criteria

• 3. PPMS not fulfilling inclusion criteria

• 4. Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or Hepatitis C

• 5. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization

• 6. Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization

• 7. Treatment with corticosteroids within the 30 days prior to randomization

• 8. Relapse occurred during the 60 days prior to randomization

• 9. 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

• 10. Severely limited life expectancy by another co-morbid illness

• 11. History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts

• 12. Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study)

• 13. eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination.

• 14. Inability to give written informed consent in accordance with research ethics board guidelines

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• Autologous Mesenchymal Stem Cells
Single dose of 1-2 x 1000000 cells/Kg body weight

Locations

Country	Name	City	State
Italy	University of Genova	Genova

Sponsors (3)

Lead Sponsor	Collaborator
Antonio Uccelli	Azienda Ospedaliera Universitaria Integrata Verona, Ospedale San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Incidence and severity of adverse events in MSC treatment group compared to placebo group.	24 weeks from the first infusion	Yes
Primary	efficacy	total number of contrast-enhancing lesions (GEL) at MRI scan	24 weeks from the first infusion	No
Secondary	Efficacy	Number of GEL counted over week 28, 36 and 48 compared with the number of GEL counted over 4, 12 and 24 weeks.	48 weeks from the first infusion	No
Secondary	Efficacy	Combined unique MRI activity (number of new or enlarging T2, or enhancing or re-enhancing lesions), volume of GEL and volume of black holes (BH) over 4, 12, 24 weeks compared between treatment groups.	24 weeks form the first infusion	No
Secondary	Efficacy	Combined unique MRI activity, volume of GEL and volume of BH over week 28, 36 and 48 compared with the same outcomes over 4, 12 and 24 weeks.	48 weeks from the first infusion	No
Secondary	Efficacy	Number of relapses in MSC treatment group vs. placebo group in the first 24 weeks and after cross-over re-treatment in the two groups.	48 weeks from the first infusion	No
Secondary	Efficacy	Time to sustained progression of disability and proportion of progression-free patients compared between treatment groups during the first 24 weeks and after cross-over	48 weeks from the first infusion	No