Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients (NSC-SPMS)

• ClinicalTrials.gov Identifier: NCT03282760
• Recruitment Status: Completed
• First Posted: September 14, 2017
• Last Update Posted: July 12, 2021
• Sponsor: Casa Sollievo della Sofferenza IRCCS
• Collaborators: Associazione Revert ONLUS; Neurocenter of Southern Switzerland; Fondazione Cellule Staminali
• Information provided by (Responsible Party): Casa Sollievo della Sofferenza IRCCS

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Secondary-progressive Multiple Sclerosis	Biological: Human Neural Stem Cells	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention 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)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 9, 2017
• Actual Primary Completion Date: May 29, 2021
• Actual Study Completion Date: May 29, 2021

Arms and Interventions

Arm	Intervention/treatment
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)	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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment Emergent AE [ Time Frame: 1 year ]
   To Evaluate the Feasibility, Safety and Tolerability of intracerebroventricular injection of allogenic hNSCs
2. Percentage of Mortality in treated patients [ Time Frame: 1 year ]
   Percentage of subjects (%) with death due to procedure (mortality correlated to treatment)

Secondary Outcome Measures :

1. Change in Functional disability [ Time Frame: Up to 1 year ]
   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.
2. Change in Functional disability [ Time Frame: Up to 1 year ]
   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.
3. Activity of Cognitive function [ Time Frame: Up to 1 year ]
   This will be measured as the mean change of the score of the RAO Brief Repeatable Battery of Neuropsychological Test, during the study period.
4. Relapses Rate [ Time Frame: Up to 1 year ]
   Relapses will be measured by the change in EDSS scale
5. Relapses Rate [ Time Frame: Up to 1 year ]
   Relapses will be measured by the Imaging evaluations
6. MS Biomarkers [ Time Frame: Up to 1 year ]
   Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)
7. Alteration in Neurophysiological parameters [ Time Frame: Up to 1 year ]
   Assessed by Evoked Potentials.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Italy

Casa Sollievo della Sofferenza - IRCCS

San Giovanni Rotondo, Foggia, Italy, 71013

Azienda Ospedaliera Santa Maria di Terni

Terni, Italy, 05100

Switzerland

Neurocentro della Svizzera Italiana, Istituto di Neurosienze cliniche della svizzera italiana, Centro sclerosi Multipla

Lugano, Switzerland, 6900

Sponsors and Collaborators

Casa Sollievo della Sofferenza IRCCS

Associazione Revert ONLUS

Neurocenter of Southern Switzerland

Fondazione Cellule Staminali

Investigators

• Study Director: Angelo L Vescovi, PhD; Casa Sollievo della Sofferenza IRCCS

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Casa Sollievo della Sofferenza IRCCS
• ClinicalTrials.gov Identifier: NCT03282760
• Other Study ID Numbers: NSC SPMS; 2015-004855-37 ( EudraCT Number )
• First Posted: September 14, 2017
• Last Update Posted: July 12, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication
• Supporting Materials: Clinical Study Report (CSR)

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Casa Sollievo della Sofferenza IRCCS:

Cell Transplantation; Neural Stem Cells

Additional relevant MeSH terms:

Neoplasm Metastasis; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Neoplastic Processes; Neoplasms; Chronic Disease; Disease Attributes