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

NCT03282760 | Completed Phase 1 DMC

• 2 other identifiers: NSC SPMS2015-004855-37
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 3

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.

Conditions

Secondary-progressive Multiple Sclerosis

Keywords

Cell Transplantation; Neural Stem Cells

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment Emergent AE

  To Evaluate the Feasibility, Safety and Tolerability of intracerebroventricular injection of allogenic hNSCs

  1 year

• Percentage of Mortality in treated patients

  Percentage of subjects (%) with death due to procedure (mortality correlated to treatment)

  1 year

Secondary Outcomes (7)

• Change in Functional disability

  Up to 1 year

• Change in Functional disability

  Up to 1 year

• Activity of Cognitive function

  Up to 1 year

• Relapses Rate

  Up to 1 year

• Relapses Rate

  Up to 1 year

Study Arms (1)

Human Neural Stem Cells Suspension

EXPERIMENTAL

Intraventricular injections of Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10,16 or 24 millions)

Biological: Human Neural Stem Cells

Interventions

Human Neural Stem Cells BIOLOGICAL

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.

Human Neural Stem Cells Suspension

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• SPMS with progressive accumulation of disability after initial relapsing course, with or without disease activity (Lublin et al. 2014).
• EDSS ≥ 6.5 and ≤ 8
• Age ≥ 18 and ≤ 60 years
• Failure of best medical treatment as judged by the treating neurologist and declared absence of therapeutic alternatives

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Casa Sollievo della Sofferenza IRCCS: lead
• Associazione Revert ONLUS: collaborator
• Neurocenter of Southern Switzerland: collaborator
• Fondazione Cellule Staminali: collaborator

Study Sites (3)

Casa Sollievo della Sofferenza - IRCCS

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Azienda Ospedaliera Santa Maria di Terni

Terni, 05100, Italy

Location

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

Lugano, 6900, Switzerland

Location

Related Publications (7)

• 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.

  PMID: 23934834 BACKGROUND

• 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.

  PMID: 25889343 BACKGROUND

• 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.

  PMID: 19798728 BACKGROUND

• 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.

  PMID: 12700753 BACKGROUND

• 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.

  PMID: 22076651 BACKGROUND

• Leone MA, Gelati M, Profico DC, Gobbi C, Pravata 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. Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis. Cell Stem Cell. 2023 Dec 7;30(12):1597-1609.e8. doi: 10.1016/j.stem.2023.11.001. Epub 2023 Nov 27.

  PMID: 38016468 DERIVED

• 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.

  PMID: 34558001 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Angelo L Vescovi, PhD

  Casa Sollievo della Sofferenza IRCCS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 9, 2017
• First Posted: September 14, 2017
• Study Start: September 9, 2017
• Primary Completion: May 29, 2021
• Study Completion: May 29, 2021
• Last Updated: July 12, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

CH (1); IT (2)