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

Secondary-progressive Multiple Sclerosis Clinical Trial

— NSC-SPMS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03282760
• Other study ID #: NSC SPMS
• Secondary ID: 2015-004855-37
• Status: Completed
• Phase: Phase 1
• Start date: September 9, 2017
• Est. completion date: May 29, 2021

Study information

• Verified date: July 2021
• Source: Casa Sollievo della Sofferenza IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 29, 2021
• Est. primary completion date: May 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. SPMS with progressive accumulation of disability after initial relapsing course, with or without disease activity (Lublin et al. 2014).

2. EDSS = 6.5 and = 8

3. 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

4. Age = 18 and = 60 years

5. Failure of best medical treatment as judged by the treating neurologist and declared absence of therapeutic alternatives

Exclusion Criteria:

1. Neurological conditions other than MS.

2. Psychiatric disorders, severe cognitive decline and personality and relational disorders.

3. History or known presence of significant systemic, infectious, oncologic or metabolic disorders.

4. Presence of any other autoimmune disease.

5. Chronic infections (HBV, HCV, HIV, tuberculosis).

6. Inability to perform MRI scans.

7. Immunomodulant/immunosuppressive treatments in the last 6 months before inclusion.

8. Current participation to other experimental studies.

9. Inability to provide informed consent.

10. Any contra-indication to lumbar puncture and the surgical procedure (e.g. use of anticoagulants)

11. Pregnancy and breast feeding.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Neoplasm Metastasis
• Sclerosis
• Secondary-progressive Multiple Sclerosis

Intervention

Biological:
• Human Neural Stem Cells
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.

Locations

Country	Name	City	State
Italy	Casa Sollievo della Sofferenza - IRCCS	San Giovanni Rotondo	Foggia
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni
Switzerland	Neurocentro della Svizzera Italiana, Istituto di Neurosienze cliniche della svizzera italiana, Centro sclerosi Multipla	Lugano

Sponsors (4)

Lead Sponsor	Collaborator
Casa Sollievo della Sofferenza IRCCS	Associazione Revert ONLUS, Fondazione Cellule Staminali, Neurocenter of Southern Switzerland

Countries where clinical trial is conducted

Italy,  Switzerland, 

References & Publications (5)

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. — View Citation

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. — View Citation

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, Sorarù 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent AE	To Evaluate the Feasibility, Safety and Tolerability of intracerebroventricular injection of allogenic hNSCs	1 year
Primary	Percentage of Mortality in treated patients	Percentage of subjects (%) with death due to procedure (mortality correlated to treatment)	1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	Relapses Rate	Relapses will be measured by the change in EDSS scale	Up to 1 year
Secondary	Relapses Rate	Relapses will be measured by the Imaging evaluations	Up to 1 year
Secondary	MS Biomarkers	Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)	Up to 1 year
Secondary	Alteration in Neurophysiological parameters	Assessed by Evoked Potentials.	Up to 1 year