Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients

Study Overview
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Brief Summary
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This will be a phase I, open, multicenter, international study performed by 3 participating centres across two countries (Italy and Switzerland). Fifteen to 24 patients affected by SPMS will be enrolled, according to a standard phase I design over 18 months. All patients will enter a 3 months run in phase. Thereafter they will receive one of four different doses of allogenic hNSCs (dose A=5 millions hNSCs; dose B=10 millions hNSCs; dose C=16 millions hNSCs; dose D=24 millions hNSCs). Following hNSCs injection, all SPMS patients will receive immunosuppression with tacrolimus for 6 months. Patients will be clinically followed monthly for 1 year and then every 6 months for the 5 years following the study completion (possibly all life long). MRI assessments will be performed monthly for the first 6 months and then every 3 months for 5 years following the study completion.

Official Title
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A Phase I Multicenter Study of Allogenic, Intracerebroventricular Human Neural Stem Cells Transplantation for the Experimental Treatment of Secondary Progressive Multiple Sclerosis Patients

Conditions
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Secondary-progressive Multiple Sclerosis

Intervention / Treatment
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* Biological: Human Neural Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SPMS with progressive accumulation of disability after initial relapsing course, with or without disease activity (Lublin et al. 2014). EDSS ≥ 6.5 and ≤ 8 EDSS progression over the 2 years prior to study start of ≥ 1.0 point for patients with EDSS =6.5 at the time of inclusion , and of ≥ 0.5 points for patients with EDSS > 6.5 at the time of inclusion Age ≥ 18 and ≤ 60 years Failure of best medical treatment as judged by the treating neurologist and declared absence of therapeutic alternatives Exclusion Criteria: Neurological conditions other than MS. Psychiatric disorders, severe cognitive decline and personality and relational disorders. History or known presence of significant systemic, infectious, oncologic or metabolic disorders. Presence of any other autoimmune disease. Chronic infections (HBV, HCV, HIV, tuberculosis). Inability to perform MRI scans. Immunomodulant/immunosuppressive treatments in the last 6 months before inclusion. Current participation to other experimental studies. Inability to provide informed consent. Any contra-indication to lumbar puncture and the surgical procedure (e.g. use of anticoagulants) Pregnancy and breast feeding.

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
Intervention Model: Sequential Assignment
Interventional Model Description: Fifteen to 24 patients affected by SPMS will be enrolled, according to a standard phase I design over 18 months. All patients will enter a 3 months run in phase. Thereafter they will receive one of four different doses of allogenic hNSCs (dose A=5 millions hNSCs; dose B=10 millionshNSCs; dose C=16 millions hNSCs; dose D=24 millions hNSCs).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Neural Stem Cells Suspension<br>Intraventricular injections of Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10,16 or 24 millions) | Biological: Human Neural Stem Cells<br>* Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10, 16 or 24 millions). hNSCs are produced by the Laboratorio Cellule Staminali of Terni according to GMP guidelines and are obtained from brain specimens of several fetal human donors from spontaneous miscarriages occurred after the 8th week after conception.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent AE | To Evaluate the Feasibility, Safety and Tolerability of intracerebroventricular injection of allogenic hNSCs | 1 year | 
| Percentage of Mortality in treated patients | Percentage of subjects (%) with death due to procedure (mortality correlated to treatment) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Functional disability | this will be measured by the change of the Expanded Disability Scale (EDSS-disability score about pyramidal, cereberral, brainstem, sensory, bowel and bladder, visual, cerebral Functional Systems) during the study period. | Up to 1 year | 
| Change in Functional disability | this will be measured by the change of the the Multiple Sclerosis Functional Composite (MSFC-scores about upper extremity function, ambulation and cognitive function) during the study period. | Up to 1 year | 
| Activity of Cognitive function | This will be measured as the mean change of the score of the RAO Brief Repeatable Battery of Neuropsychological Test, during the study period. | Up to 1 year | 
| Relapses Rate | Relapses will be measured by the change in EDSS scale | Up to 1 year | 
| Relapses Rate | Relapses will be measured by the Imaging evaluations | Up to 1 year | 
| MS Biomarkers | Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments) | Up to 1 year | 
| Alteration in Neurophysiological parameters | Assessed by Evoked Potentials. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell Transplantation, Neural Stem Cells