Clinical trial NCT03282760: Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Secondary-progressive Multiple Sclerosis
Keywords: Cell Transplantation
Neural Stem Cells
Lead sponsor: Casa Sollievo della Sofferenza IRCCS
Sponsor class: OTHER
Collaborators: name: Associazione Revert ONLUS
name: Neurocenter of Southern Switzerland
name: Fondazione Cellule Staminali
First posted: 2017-09-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of Treatment Emergent AE
timeFrame: 1 year
measure: Percentage of Mortality in treated patients
timeFrame: 1 year
Secondary outcomes:
measure: Change in Functional disability
timeFrame: Up to 1 year
measure: Change in Functional disability
timeFrame: Up to 1 year
measure: Activity of Cognitive function
timeFrame: Up to 1 year
measure: Relapses Rate
timeFrame: Up to 1 year
measure: Relapses Rate
timeFrame: Up to 1 year
measure: MS Biomarkers
timeFrame: Up to 1 year
measure: Alteration in Neurophysiological parameters
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza - IRCCS
state: Foggia
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Lugano
country: Switzerland
facility: Neurocentro della Svizzera Italiana, Istituto di Neurosienze cliniche della svizzera italiana, Centro sclerosi Multipla
Study officials:
affiliation: Casa Sollievo della Sofferenza IRCCS
name: Angelo L Vescovi, PhD
role: STUDY_DIRECTOR
References:
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.
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, 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.
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.
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. doi: 10.1038/nature01552.
citation: 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.
citation: 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.