- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03282760
Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients (NSC-SPMS)
A Phase I Multicenter Study of Allogenic, Intracerebroventricular Human Neural Stem Cells Transplantation for the Experimental Treatment of Secondary Progressive Multiple Sclerosis Patients
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Terni, Italy, 05100
- Azienda Ospedaliera Santa Maria di Terni
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Foggia
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San Giovanni Rotondo, Foggia, Italy, 71013
- Casa Sollievo della Sofferenza - IRCCS
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Lugano, Switzerland, 6900
- Neurocentro della Svizzera Italiana, Istituto di Neurosienze cliniche della svizzera italiana, Centro sclerosi Multipla
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Human Neural Stem Cells Suspension
Intraventricular injections of Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10,16 or 24 millions)
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of Treatment Emergent AE
Time Frame: 1 year
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To Evaluate the Feasibility, Safety and Tolerability of intracerebroventricular injection of allogenic hNSCs
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1 year
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Percentage of Mortality in treated patients
Time Frame: 1 year
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Percentage of subjects (%) with death due to procedure (mortality correlated to treatment)
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1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Functional disability
Time Frame: Up to 1 year
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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.
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Up to 1 year
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Change in Functional disability
Time Frame: Up to 1 year
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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.
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Up to 1 year
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Activity of Cognitive function
Time Frame: Up to 1 year
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This will be measured as the mean change of the score of the RAO Brief Repeatable Battery of Neuropsychological Test, during the study period.
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Up to 1 year
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Relapses Rate
Time Frame: Up to 1 year
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Relapses will be measured by the change in EDSS scale
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Up to 1 year
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Relapses Rate
Time Frame: Up to 1 year
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Relapses will be measured by the Imaging evaluations
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Up to 1 year
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MS Biomarkers
Time Frame: Up to 1 year
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Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)
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Up to 1 year
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Alteration in Neurophysiological parameters
Time Frame: Up to 1 year
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Assessed by Evoked Potentials.
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Up to 1 year
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: Angelo L Vescovi, PhD, Casa Sollievo Della Sofferenza IRCCS
Publications and helpful links
General Publications
- Gelati M, Profico D, Projetti-Pensi M, Muzi G, Sgaravizzi G, Vescovi AL. Culturing and expansion of "clinical grade" precursors cells from the fetal human central nervous system. Methods Mol Biol. 2013;1059:65-77. doi: 10.1007/978-1-62703-574-3_6.
- Mazzini L, Gelati M, Profico DC, Sgaravizzi G, Projetti Pensi M, Muzi G, Ricciolini C, Rota Nodari L, Carletti S, Giorgi C, Spera C, Domenico F, Bersano E, Petruzzelli F, Cisari C, Maglione A, Sarnelli MF, Stecco A, Querin G, Masiero S, Cantello R, Ferrari D, Zalfa C, Binda E, Visioli A, Trombetta D, Novelli A, Torres B, Bernardini L, Carriero A, Prandi P, Servo S, Cerino A, Cima V, Gaiani A, Nasuelli N, Massara M, Glass J, Soraru G, Boulis NM, Vescovi AL. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med. 2015 Jan 27;13:17. doi: 10.1186/s12967-014-0371-2.
- Pluchino S, Gritti A, Blezer E, Amadio S, Brambilla E, Borsellino G, Cossetti C, Del Carro U, Comi G, 't Hart B, Vescovi A, Martino G. Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Ann Neurol. 2009 Sep;66(3):343-54. doi: 10.1002/ana.21745.
- Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature. 2003 Apr 17;422(6933):688-94. doi: 10.1038/nature01552.
- Ferrari D, Zalfa C, Nodari LR, Gelati M, Carlessi L, Delia D, Vescovi AL, De Filippis L. Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model. Cell Mol Life Sci. 2012 Apr;69(7):1193-210. doi: 10.1007/s00018-011-0873-5. Epub 2011 Nov 11.
- Gelati M, Profico DC, Ferrari D, Vescovi AL. Culturing and Expansion of "Clinical Grade" Neural Stem Cells from the Fetal Human Central Nervous System. Methods Mol Biol. 2022;2389:57-66. doi: 10.1007/978-1-0716-1783-0_5.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Neoplasms
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Neoplastic Processes
- Multiple Sclerosis
- Multiple Sclerosis, Chronic Progressive
- Sclerosis
- Neoplasm Metastasis
Other Study ID Numbers
- NSC SPMS
- 2015-004855-37 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Supporting Information Type
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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