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

Primary Purpose

Secondary-progressive Multiple Sclerosis

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Human Neural Stem Cells

About this trial

This is an interventional treatment trial for Secondary-progressive Multiple Sclerosis focused on measuring Cell Transplantation, Neural Stem Cells

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Casa Sollievo della Sofferenza - IRCCS
Azienda Ospedaliera Santa Maria di Terni
Neurocentro della Svizzera Italiana, Istituto di Neurosienze cliniche della svizzera italiana, Centro sclerosi Multipla

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Human Neural Stem Cells Suspension

Arm Description

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

Outcomes

Primary Outcome Measures

Incidence of Treatment Emergent AE

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

Percentage of Mortality in treated patients

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

Secondary Outcome Measures

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.

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.

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.

Relapses Rate

Relapses will be measured by the change in EDSS scale

Relapses Rate

Relapses will be measured by the Imaging evaluations

MS Biomarkers

Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)

Alteration in Neurophysiological parameters

Assessed by Evoked Potentials.

Full Information

NCT ID

NCT03282760

First Posted

August 9, 2017

Last Updated

July 9, 2021

Sponsor

Casa Sollievo della Sofferenza IRCCS

Collaborators

Associazione Revert ONLUS, Neurocenter of Southern Switzerland, Fondazione Cellule Staminali

1. Study Identification

Unique Protocol Identification Number

NCT03282760

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

September 9, 2017 (Actual)

Primary Completion Date

May 29, 2021 (Actual)

Study Completion Date

May 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Casa Sollievo della Sofferenza IRCCS

Collaborators

Associazione Revert ONLUS, Neurocenter of Southern Switzerland, Fondazione Cellule Staminali

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Secondary-progressive Multiple Sclerosis

Keywords

Cell Transplantation, Neural Stem Cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Human Neural Stem Cells Suspension

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Human Neural Stem Cells

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of Treatment Emergent AE

Description

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

Time Frame

1 year

Title

Percentage of Mortality in treated patients

Description

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

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Change in Functional disability

Description

Time Frame

Up to 1 year

Title

Change in Functional disability

Description

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.

Time Frame

Up to 1 year

Title

Activity of Cognitive function

Description

This will be measured as the mean change of the score of the RAO Brief Repeatable Battery of Neuropsychological Test, during the study period.

Time Frame

Up to 1 year

Title

Relapses Rate

Description

Relapses will be measured by the change in EDSS scale

Time Frame

Up to 1 year

Title

Relapses Rate

Description

Relapses will be measured by the Imaging evaluations

Time Frame

Up to 1 year

Title

MS Biomarkers

Description

Investigation of potential candidate biomarkers able to monitor disease activity and predict clinical course in MS (Neurofilaments)

Time Frame

Up to 1 year

Title

Alteration in Neurophysiological parameters

Description

Assessed by Evoked Potentials.

Time Frame

Up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: SPMS with progressive accumulation of disability after initial relapsing course, with or without disease activity (Lublin et al. 2014). EDSS ≥ 6.5 and ≤ 8 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 Age ≥ 18 and ≤ 60 years Failure of best medical treatment as judged by the treating neurologist and declared absence of therapeutic alternatives Exclusion Criteria: 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. Immunomodulant/immunosuppressive treatments in the last 6 months before inclusion. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Angelo L Vescovi, PhD

Organizational Affiliation

Casa Sollievo della Sofferenza IRCCS

Official's Role

Study Director

Facility Information:

Facility Name

Casa Sollievo della Sofferenza - IRCCS

City

San Giovanni Rotondo

State/Province

Foggia

ZIP/Postal Code

71013

Country

Italy

Facility Name

Azienda Ospedaliera Santa Maria di Terni

City

Terni

ZIP/Postal Code

05100

Country

Italy

Facility Name

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

City

Lugano

ZIP/Postal Code

6900

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All IPD that underlie results in a publication

Citations:

PubMed Identifier

23934834

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.

Results Reference

background

PubMed Identifier

25889343

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.

Results Reference

background

PubMed Identifier

19798728

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.

Results Reference

background

PubMed Identifier

12700753

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.

Results Reference

background

PubMed Identifier

22076651

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.

Results Reference

background

PubMed Identifier

34558001

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.

Results Reference

derived

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

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