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

Conditions

Secondary-progressive Multiple Sclerosis

Keywords

Cell Transplantation, Neural Stem Cells

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.

Leone MA, Gelati M, Profico DC, Gobbi C, Pravatà E, Copetti M, Conti C, Abate L, Amoruso L, Apollo F, Balzano RF, Bicchi I, Carella M, Ciampini A, Colosimo C, Crociani P, D'Aloisio G, Di Viesti P, Ferrari D, Fogli D, Fontana A, Frondizi D, Grespi V, Kuhle J, Laborante A, Lombardi I, Muzi G, Paci F, Placentino G, Popolizio T, Ricciolini C, Sabatini S, Silveri G, Spera C, Stephenson D, Stipa G, Tinella E, Zarrelli M, Zecca C, Ventura Y, D'Alessandro A, Peruzzotti-Jametti L, Pluchino S, Vescovi AL.

2023-11-2725 citations

10.1016/j.stem.2023.11.001

Human Neural Stem Cell-Based Drug Product: Clinical and Nonclinical Characterization

Daniela Celeste Profico, Maurizio Gelati, Daniela Ferrari, Giada Sgaravizzi, Claudia Ricciolini et al. (13 authors)

International Journal of Molecular Sciences2022-11-0313 citations

10.3390/ijms232113425

Culturing and Expansion of "Clinical Grade" Neural Stem Cells from the Fetal Human Central Nervous System.

Gelati M, Profico DC, Ferrari D, Vescovi AL.

2022-01-014 citations

10.1007/978-1-0716-1783-0_5

Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats

Cristina Zalfa, Laura Rota Nodari, Elena Vacchi, Maurizio Gelati, Daniela Celeste Profico et al. (21 authors)

Cell Death and Disease2019-04-2542 citations

10.1038/s41419-019-1582-5

Interventions

BIOLOGICALHuman 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.

Study design

Allocation

NA

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

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).

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

No

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Relapses Rate	Up to 1 year	Relapses will be measured by the change in EDSS scale
Change in Functional disability	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.
Alteration in Neurophysiological parameters	Up to 1 year	Assessed by Evoked Potentials.
MS Biomarkers	Up to 1 year	Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)
Activity of Cognitive function	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.

Countries

Italy, Switzerland

Outcome results

None listed