MEsenchymal Stem Cell Therapy for CAnadian MS Patients
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Multiple Sclerosis
- Sponsor
- Ottawa Hospital Research Institute
- Enrollment
- 31
- Locations
- 2
- Primary Endpoint
- Efficacy
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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).
Detailed Description
The mechanism of action of Mesenchymal Stem Cells (MSCs) 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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •RRMS not fulfilling inclusion criteria
- •SPMS not fulfilling inclusion criteria
- •PPMS not fulfilling inclusion criteria
- •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
Outcomes
Primary Outcomes
Efficacy
Time Frame: 24 weeks from first infusion
Total number of gadolinium-enhancing lesions (GEL) on MRI scan
Safety
Time Frame: 24 weeks from first infusion
Incidence and severity of adverse events in MSC treatment group compared to placebo group
Secondary Outcomes
- Efficacy(48 weeks from first infusion)