<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03269071</url>
  </required_header>
  <id_info>
    <org_study_id>2016-002020-86 (EudraCT)</org_study_id>
    <nct_id>NCT03269071</nct_id>
  </id_info>
  <brief_title>Neural Stem Cell Transplantation in Multiple Sclerosis Patients</brief_title>
  <acronym>STEMS</acronym>
  <official_title>Neural Stem Cell Transplantation in Multiple Sclerosis Patient: a Phase I Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondazione Italiana Sclerosi Multipla</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>IRCCS San Raffaele</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase I study evaluating the feasibility, safety and tolerability of intrathecally&#xD;
      administered human Neural Stem Cells (hNSCs), at an escalating dose ranging from 0.7x10^6±10%&#xD;
      cells to 5.7x10^6±10% cells/kg of body weight, in patients affected by Progressive Multiple&#xD;
      Sclerosis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, monocentric, national, therapeutic exploratory, phase I, not&#xD;
      randomized, open label, not controlled, single dose escalation clinical trial.&#xD;
&#xD;
      Each subject will participate in the study for approximately 96 weeks. Participation will&#xD;
      include a screening evaluation between -28 and -7 days before the Advance Therapy&#xD;
      Investigational Medicinal Products (ATIMP) administration.&#xD;
&#xD;
      A follow-up with clinical visits will be performed from 1 to 96 weeks.&#xD;
&#xD;
      The protocol will consist of a total of four treatment cohorts (TCs), labeled from A to D,&#xD;
      each receiving a single escalating dose of allogenic fetal-derived human Neural Stem Cells&#xD;
      (hNSCs) injected intrathecally, as it follows:&#xD;
&#xD;
        -  TC-A: 0.7x10^6 ± 10% cells/kg of body weight;&#xD;
&#xD;
        -  TC-B: 1.4x10^6 ± 10% cells/kg of body weight;&#xD;
&#xD;
        -  TC-C: 2.8x10^6 ± 10% cells/kg of body weight;&#xD;
&#xD;
        -  TC-D: 5.7x10^6 ± 10% cells/kg of body weight.&#xD;
&#xD;
      The intrathecal injection of hNSCs will be performed in a hospitalized setting. The trial&#xD;
      will start with TC-A and will go through the subsequent enrolment of patients to be included&#xD;
      in TCs from B to D.&#xD;
&#xD;
      Each cohort will consist of three patients at minimum. In case of safety issue the number in&#xD;
      each TC will be increased to six patients.&#xD;
&#xD;
      After the inclusion of the first patient of the TC the investigators will wait at least 14&#xD;
      days to treat the second patient. The same interval time will be used for all the following&#xD;
      patient within the same TC. After the inclusion of all the planned patients within a TC and&#xD;
      with no Dose Limiting Toxicity (DLT) within the TC, the investigators will wait at least 3&#xD;
      months before switching to the upper TC. In case of 1 DLT within the TC, the cohort will be&#xD;
      extended to six patients. If another DLT will be observed, the current dosage will be&#xD;
      considered excessive and the immediate lower dosage will be considered the Maximum Tolerated&#xD;
      Dose (MTD).&#xD;
&#xD;
      The safety monitoring board will review all safety date in the case of evaluated Adverse&#xD;
      Event (AE) ≥ 3 &quot;possibly related to human Neural Stem Cells&quot; by investigators and in any case&#xD;
      before the shifts between TCs.&#xD;
&#xD;
      This approach will be repeated for every TC up to the end of the study. At the end of the&#xD;
      total follow-up, a long term follow up is planned for all enrolled and treated patients in&#xD;
      the study, in accordance with the national applicable laws and the international guidelines.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 17, 2017</start_date>
  <completion_date type="Actual">July 31, 2021</completion_date>
  <primary_completion_date type="Actual">July 31, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>SHORT TERM (0-24 hours) Overall survival</measure>
    <time_frame>0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of patients alive all over the trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SHORT TERM (0-24 hours) Overall safety and tolerability measured by Adverse Event (AE) recording</measure>
    <time_frame>0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of AEs in alive patients all over the trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SHORT TERM (0-24 hours) Changes in neurological conditions not related to disease</measure>
    <time_frame>0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of changes in neurological conditions not related to disease of alive patients all over the trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SHORT TERM (0-24 hours) Proportion of successful intrathecal administration procedure (feasibility)</measure>
    <time_frame>0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of successful intrathecal administration procedures versus all intrathecal administration procedures in the whole trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MID TERM (day 1- day 14) Overall survival</measure>
    <time_frame>from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of alive patients in the whole trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MID TERM (day 1- day 14) Overall safety and tolerability measured by AE recording</measure>
    <time_frame>from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of AEs of alive patients in the whole trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MID TERM (day 1- day 14) Changes in neurological conditions not related to disease</measure>
    <time_frame>from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of changes in neurological conditions not related to disease in alive patients of the whole trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>LONG TERM (day 15 - week 96) Overall survival</measure>
    <time_frame>from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of alive patients in the whole trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>LONG TERM (day 15 - week 96) Overall safety and tolerability measured by AE recording</measure>
    <time_frame>from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of AEs in alive patients of the whole trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Long term incidence of malignancies</measure>
    <time_frame>from day 0 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Incidence of malignancies in alive patients of the whole trial</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of changes in quality of life measures</measure>
    <time_frame>12, 24, 48, 72 and 96 weeks</time_frame>
    <description>Health-related quality of life will be assessed by standardized questionnaires</description>
  </primary_outcome>
  <primary_outcome>
    <measure>LONG TERM (day 15 - week 96) Changes in neurological conditions not related to the disease</measure>
    <time_frame>from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)</time_frame>
    <description>Number of changes in the neurological conditions not related to disease in alive patients of the whole trial</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Progressive Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Treatment Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>See Study Description&#xD;
TC-A: 0.7 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>See Study Description&#xD;
TC-B: 1.4 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>See Study Description&#xD;
TC-C: 2.8 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Cohort D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>See Study Description&#xD;
TC-D: 5.7 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>human fetal-derived Neural Stem Cells (hNSCs)</intervention_name>
    <description>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).&#xD;
For dosage indications, see specific Treatment Cohorts (TC), from A to D.&#xD;
The product will be administered intrathecally through lumbar puncture.</description>
    <arm_group_label>Treatment Cohort A</arm_group_label>
    <arm_group_label>Treatment Cohort B</arm_group_label>
    <arm_group_label>Treatment Cohort C</arm_group_label>
    <arm_group_label>Treatment Cohort D</arm_group_label>
    <other_name>human Neural Stem Cells (hNCSs)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signature of the informed consent by the patient or patients' legal tutors&#xD;
&#xD;
          2. Age 18 to 55 years&#xD;
&#xD;
          3. Diagnosis of a. Progressive MS as per the revised MC Donald 2010 criteria with a&#xD;
             progressive course according to 2013 Lublin phenotypes classification (PMS) with&#xD;
             failure or intolerance to all approved therapies according to the disease course or&#xD;
             without any alternative approved therapy&#xD;
&#xD;
          4. Evidence of progression of disease defined by an increase of ≥ 0.5 Expanded Disability&#xD;
             Status Scale (EDSS) points in the last 12 months&#xD;
&#xD;
          5. Disease duration 2 to 20 years (included)&#xD;
&#xD;
          6. Expanded Disability Status Scale (EDSS) ≥ 6.5&#xD;
&#xD;
          7. Presence of oligoclonal band in the cerebrospinal fluid (CSF) is required for Primary&#xD;
             Progressive MS&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        They will be excluded from the study patients:&#xD;
&#xD;
          1. with any active or chronic infection or diseases other than MS including but not&#xD;
             limited to infection with HIV1-2, Hepatitis B or Hepatitis C and tuberculosis or&#xD;
             immune deficiency syndromes;&#xD;
&#xD;
          2. treated with any immunosuppressive therapy, including but not limited to natalizumab&#xD;
             and fingolimod, within the 3 months prior to screening;&#xD;
&#xD;
          3. treated with interferon-beta or glatiramer acetate within the 30 days prior to&#xD;
             screening;&#xD;
&#xD;
          4. treated with corticosteroids within the 30 days prior to screening;&#xD;
&#xD;
          5. if relapse occurred during the 30 days prior to screening;&#xD;
&#xD;
          6. with contraindications for or intolerance to any medication, treatments and procedures&#xD;
             that will be used in the study;&#xD;
&#xD;
          7. pregnant or in lactation or of childbearing age who are not willing to use a&#xD;
             contraceptive method effective* for the entire duration of the study;&#xD;
&#xD;
          8. who, in the opinion of the investigator, showing any condition that would preclude&#xD;
             study participation.&#xD;
&#xD;
               -  refer to guideline http://www.hma.eu/fileadmin/dateien/Human_Medicines/01&#xD;
                  About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gianvito Martino</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS San Raffaele</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <state>MI</state>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>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.</citation>
    <PMID>22837038</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>20404843</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>19798728</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>12700753</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>16015332</PMID>
  </results_reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>September 2, 2021</last_update_submitted>
  <last_update_submitted_qc>September 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS San Raffaele</investigator_affiliation>
    <investigator_full_name>Gianvito MARTINO</investigator_full_name>
    <investigator_title>Prof.</investigator_title>
  </responsible_party>
  <keyword>Multiple Sclerosis</keyword>
  <keyword>Cell Therapy</keyword>
  <keyword>Human Neural Stem Cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>It is not yet known the best way to exploit the Individual Participant data (IPD) that will become available</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT03269071/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03269071
org study id: 2016-002020-86 (EudraCT)
nct id: NCT03269071
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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
This is a prospective, monocentric, national, therapeutic exploratory, phase I, not
      randomized, open label, not controlled, single dose escalation clinical trial.

      Each subject will participate in the study for approximately 96 weeks. Participation will
      include a screening evaluation between -28 and -7 days before the Advance Therapy
      Investigational Medicinal Products (ATIMP) administration.

      A follow-up with clinical visits will be performed from 1 to 96 weeks.

      The protocol will consist of a total of four treatment cohorts (TCs), labeled from A to D,
      each receiving a single escalating dose of allogenic fetal-derived human Neural Stem Cells
      (hNSCs) injected intrathecally, as it follows:

        -  TC-A: 0.7x10^6 ± 10% cells/kg of body weight;

        -  TC-B: 1.4x10^6 ± 10% cells/kg of body weight;

        -  TC-C: 2.8x10^6 ± 10% cells/kg of body weight;

        -  TC-D: 5.7x10^6 ± 10% cells/kg of body weight.

      The intrathecal injection of hNSCs will be performed in a hospitalized setting. The trial
      will start with TC-A and will go through the subsequent enrolment of patients to be included
      in TCs from B to D.

      Each cohort will consist of three patients at minimum. In case of safety issue the number in
      each TC will be increased to six patients.

      After the inclusion of the first patient of the TC the investigators will wait at least 14
      days to treat the second patient. The same interval time will be used for all the following
      patient within the same TC. After the inclusion of all the planned patients within a TC and
      with no Dose Limiting Toxicity (DLT) within the TC, the investigators will wait at least 3
      months before switching to the upper TC. In case of 1 DLT within the TC, the cohort will be
      extended to six patients. If another DLT will be observed, the current dosage will be
      considered excessive and the immediate lower dosage will be considered the Maximum Tolerated
      Dose (MTD).

      The safety monitoring board will review all safety date in the case of evaluated Adverse
      Event (AE) ≥ 3 "possibly related to human Neural Stem Cells" by investigators and in any case
      before the shifts between TCs.

      This approach will be repeated for every TC up to the end of the study. At the end of the
      total follow-up, a long term follow up is planned for all enrolled and treated patients in
      the study, in accordance with the national applicable laws and the international guidelines.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: SHORT TERM (0-24 hours) Overall survival
time frame: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of patients alive all over the trial
measure: SHORT TERM (0-24 hours) Overall safety and tolerability measured by Adverse Event (AE) recording
time frame: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of AEs in alive patients all over the trial
measure: SHORT TERM (0-24 hours) Changes in neurological conditions not related to disease
time frame: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of changes in neurological conditions not related to disease of alive patients all over the trial
measure: SHORT TERM (0-24 hours) Proportion of successful intrathecal administration procedure (feasibility)
time frame: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of successful intrathecal administration procedures versus all intrathecal administration procedures in the whole trial
measure: MID TERM (day 1- day 14) Overall survival
time frame: from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of alive patients in the whole trial
measure: MID TERM (day 1- day 14) Overall safety and tolerability measured by AE recording
time frame: from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of AEs of alive patients in the whole trial
measure: MID TERM (day 1- day 14) Changes in neurological conditions not related to disease
time frame: from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of changes in neurological conditions not related to disease in alive patients of the whole trial
measure: LONG TERM (day 15 - week 96) Overall survival
time frame: from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of alive patients in the whole trial
measure: LONG TERM (day 15 - week 96) Overall safety and tolerability measured by AE recording
time frame: from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of AEs in alive patients of the whole trial
measure: Long term incidence of malignancies
time frame: from day 0 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Incidence of malignancies in alive patients of the whole trial
measure: Evaluation of changes in quality of life measures
time frame: 12, 24, 48, 72 and 96 weeks
description: Health-related quality of life will be assessed by standardized questionnaires
measure: LONG TERM (day 15 - week 96) Changes in neurological conditions not related to the disease
time frame: from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
description: Number of changes in the neurological conditions not related to disease in alive patients of the whole trial
arm group label: Treatment Cohort A
arm group type: Experimental
description: See Study Description
TC-A: 0.7 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
arm group label: Treatment Cohort B
arm group type: Experimental
description: See Study Description
TC-B: 1.4 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
arm group label: Treatment Cohort C
arm group type: Experimental
description: See Study Description
TC-C: 2.8 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
arm group label: Treatment Cohort D
arm group type: Experimental
description: See Study Description
TC-D: 5.7 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
intervention type: Drug
intervention name: human fetal-derived Neural Stem Cells (hNSCs)
description: 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.
arm group label: Treatment Cohort A
arm group label: Treatment Cohort B
arm group label: Treatment Cohort C
arm group label: Treatment Cohort D
other name: human Neural Stem Cells (hNCSs)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Gianvito Martino
role: Principal Investigator
affiliation: IRCCS San Raffaele
facility: 
country: Italy
citation: 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
citation: 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
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.
PMID: 19798728
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.
PMID: 12700753
citation: 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
responsible party type: Principal Investigator
investigator affiliation: IRCCS San Raffaele
investigator full name: Gianvito MARTINO
investigator title: Prof.
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Chronic Progressive
mesh term: Sclerosis
sharing ipd: No
ipd description: It is not yet known the best way to exploit the Individual Participant data (IPD) that will become available
provided document: 