Neural Stem Cell Transplantation in Multiple Sclerosis Patients

NCT03269071 | Completed Phase 1 DMC

• 1 other identifier: 2016-002020-86 (EudraCT)
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study evaluating the feasibility, safety and tolerability of intrathecally administered human Neural Stem Cells (hNSCs), at an escalating dose ranging from 0.7x10\^6±10% cells to 5.7x10\^6±10% cells/kg of body weight, in patients affected by Progressive Multiple Sclerosis

Conditions

Progressive Multiple Sclerosis

Keywords

Multiple Sclerosis; Cell Therapy; Human Neural Stem Cells

Outcome Measures

Primary Outcomes (12)

• SHORT TERM (0-24 hours) Overall survival

  Number of patients alive all over the trial

  0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)

• SHORT TERM (0-24 hours) Overall safety and tolerability measured by Adverse Event (AE) recording

  Number of AEs in alive patients all over the trial

  0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)

• SHORT TERM (0-24 hours) Changes in neurological conditions not related to disease

  Number of changes in neurological conditions not related to disease of alive patients all over the trial

  0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)

• SHORT TERM (0-24 hours) Proportion of successful intrathecal administration procedure (feasibility)

  Number of successful intrathecal administration procedures versus all intrathecal administration procedures in the whole trial

  0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)

• MID TERM (day 1- day 14) Overall survival

  Number of alive patients in the whole trial

  from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)

• MID TERM (day 1- day 14) Overall safety and tolerability measured by AE recording

  Number of AEs of alive patients in the whole trial

  from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)

• MID TERM (day 1- day 14) Changes in neurological conditions not related to disease

  Number of changes in neurological conditions not related to disease in alive patients of the whole trial

  from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)

• LONG TERM (day 15 - week 96) Overall survival

  Number of alive patients in the whole trial

  from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)

• LONG TERM (day 15 - week 96) Overall safety and tolerability measured by AE recording

  Number of AEs in alive patients of the whole trial

  from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)

• Long term incidence of malignancies

  Incidence of malignancies in alive patients of the whole trial

  from day 0 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)

• Evaluation of changes in quality of life measures

  Health-related quality of life will be assessed by standardized questionnaires

  12, 24, 48, 72 and 96 weeks

• LONG TERM (day 15 - week 96) Changes in neurological conditions not related to the disease

  Number of changes in the neurological conditions not related to disease in alive patients of the whole trial

  from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)

Study Arms (4)

Treatment Cohort A

EXPERIMENTAL

See Study Description TC-A: 0.7 x 10\^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight

Drug: human fetal-derived Neural Stem Cells (hNSCs)

Treatment Cohort B

EXPERIMENTAL

See Study Description TC-B: 1.4 x 10\^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight

Drug: human fetal-derived Neural Stem Cells (hNSCs)

Treatment Cohort C

EXPERIMENTAL

See Study Description TC-C: 2.8 x 10\^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight

Drug: human fetal-derived Neural Stem Cells (hNSCs)

Treatment Cohort D

EXPERIMENTAL

See Study Description TC-D: 5.7 x 10\^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight

Drug: human fetal-derived Neural Stem Cells (hNSCs)

Interventions

human fetal-derived Neural Stem Cells (hNSCs) DRUG

The Drug Product (DP) can be classified as an ATIMP belonging to the class of Cell Therapy Medicinal Products (EU law). The ATIMP consists of human fetal-derived Neural Stem Cells (hNSCs) re-suspended in their final formulation medium as defined in the Investigational Medical Product Dossier (IMPD). For dosage indications, see specific Treatment Cohorts (TC), from A to D. The product will be administered intrathecally through lumbar puncture.

Also known as: human Neural Stem Cells (hNCSs)

Treatment Cohort A; Treatment Cohort B; Treatment Cohort C; Treatment Cohort D

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signature of the informed consent by the patient or patients' legal tutors
• Age 18 to 55 years
• Diagnosis of a. Progressive MS as per the revised MC Donald 2010 criteria with a progressive course according to 2013 Lublin phenotypes classification (PMS) with failure or intolerance to all approved therapies according to the disease course or without any alternative approved therapy
• Evidence of progression of disease defined by an increase of ≥ 0.5 Expanded Disability Status Scale (EDSS) points in the last 12 months
• Disease duration 2 to 20 years (included)
• Expanded Disability Status Scale (EDSS) ≥ 6.5
• Presence of oligoclonal band in the cerebrospinal fluid (CSF) is required for Primary Progressive MS

You may not qualify if:

• They will be excluded from the study patients:
• with any active or chronic infection or diseases other than MS including but not limited to infection with HIV1-2, Hepatitis B or Hepatitis C and tuberculosis or immune deficiency syndromes;
• treated with any immunosuppressive therapy, including but not limited to natalizumab and fingolimod, within the 3 months prior to screening;
• treated with interferon-beta or glatiramer acetate within the 30 days prior to screening;
• treated with corticosteroids within the 30 days prior to screening;
• if relapse occurred during the 30 days prior to screening;
• with contraindications for or intolerance to any medication, treatments and procedures that will be used in the study;
• pregnant or in lactation or of childbearing age who are not willing to use a contraceptive method effective\* for the entire duration of the study;
• who, in the opinion of the investigator, showing any condition that would preclude study participation.
• refer to guideline http://www.hma.eu/fileadmin/dateien/Human\_Medicines/01 About\_HMA/Working\_Groups/CTFG/2014\_09\_HMA\_CTFG\_Contraception.pdf

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Fondazione Italiana Sclerosi Multipla: collaborator

Study Sites (1)

IRCCS Ospedale San Raffaele

Milan, MI, 20132, Italy

Location

Related Publications (6)

• Kokaia Z, Martino G, Schwartz M, Lindvall O. Cross-talk between neural stem cells and immune cells: the key to better brain repair? Nat Neurosci. 2012 Jul 26;15(8):1078-87. doi: 10.1038/nn.3163.

  PMID: 22837038 RESULT

• Martino G, Franklin RJ, Baron Van Evercooren A, Kerr DA; Stem Cells in Multiple Sclerosis (STEMS) Consensus Group. Stem cell transplantation in multiple sclerosis: current status and future prospects. Nat Rev Neurol. 2010 May;6(5):247-55. doi: 10.1038/nrneurol.2010.35. Epub 2010 Apr 20.

  PMID: 20404843 RESULT

• 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 RESULT

• 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 RESULT

• Pluchino S, Zanotti L, Rossi B, Brambilla E, Ottoboni L, Salani G, Martinello M, Cattalini A, Bergami A, Furlan R, Comi G, Constantin G, Martino G. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature. 2005 Jul 14;436(7048):266-71. doi: 10.1038/nature03889.

  PMID: 16015332 RESULT

• Genchi A, Brambilla E, Sangalli F, Radaelli M, Bacigaluppi M, Furlan R, Andolfo A, Drago D, Magagnotti C, Scotti GM, Greco R, Vezzulli P, Ottoboni L, Bonopane M, Capilupo D, Ruffini F, Belotti D, Cabiati B, Cesana S, Matera G, Leocani L, Martinelli V, Moiola L, Vago L, Panina-Bordignon P, Falini A, Ciceri F, Uglietti A, Sormani MP, Comi G, Battaglia MA, Rocca MA, Storelli L, Pagani E, Gaipa G, Martino G. Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study. Nat Med. 2023 Jan;29(1):75-85. doi: 10.1038/s41591-022-02097-3. Epub 2023 Jan 9.

  PMID: 36624312 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Condition Hierarchy (Ancestors)

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

• Gianvito Martino

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: August 30, 2017
• First Posted: August 31, 2017
• Study Start: May 17, 2017
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2021
• Last Updated: September 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)