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Neural Stem Cell Transplantation in Multiple Sclerosis Patients (STEMS)

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ClinicalTrials.gov Identifier: NCT03269071
Recruitment Status : Enrolling by invitation
First Posted : August 31, 2017
Last Update Posted : February 26, 2019
Sponsor:
Collaborator:
Fondazione Italiana Sclerosi Multipla
Information provided by (Responsible Party):
Gianvito MARTINO, IRCCS San Raffaele

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

Condition or disease Intervention/treatment Phase
Progressive Multiple Sclerosis Drug: human fetal-derived Neural Stem Cells (hNSCs) Phase 1

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neural Stem Cell Transplantation in Multiple Sclerosis Patient: a Phase I Study
Actual Study Start Date : May 17, 2017
Estimated Primary Completion Date : August 15, 2020
Estimated Study Completion Date : August 15, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Cohort A

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)

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.

Other Name: human Neural Stem Cells (hNCSs)

Experimental: Treatment Cohort B

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)

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.

Other Name: human Neural Stem Cells (hNCSs)

Experimental: Treatment Cohort C

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)

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.

Other Name: human Neural Stem Cells (hNCSs)

Experimental: Treatment Cohort D

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)

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.

Other Name: human Neural Stem Cells (hNCSs)




Primary Outcome Measures :
  1. SHORT TERM (0-24 hours) Overall survival [ Time Frame: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs) ]
    Number of patients alive all over the trial

  2. 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) ]
    Number of AEs in alive patients all over the trial

  3. 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) ]
    Number of changes in neurological conditions not related to disease of alive patients all over the trial

  4. 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) ]
    Number of successful intrathecal administration procedures versus all intrathecal administration procedures in the whole trial

  5. MID TERM (day 1- day 14) Overall survival [ Time Frame: from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs) ]
    Number of alive patients in the whole trial

  6. 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) ]
    Number of AEs of alive patients in the whole trial

  7. 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) ]
    Number of changes in neurological conditions not related to disease in alive patients of the whole trial

  8. 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) ]
    Number of alive patients in the whole trial

  9. 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) ]
    Number of AEs in alive patients of the whole trial

  10. Long term incidence of malignancies [ Time Frame: from day 0 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs) ]
    Incidence of malignancies in alive patients of the whole trial

  11. Evaluation of changes in quality of life measures [ Time Frame: 12, 24, 48, 72 and 96 weeks ]
    Health-related quality of life will be assessed by standardized questionnaires

  12. 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) ]
    Number of changes in the neurological conditions not related to disease in alive patients of the whole trial



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signature of the informed consent by the patient or patients' legal tutors
  2. Age 18 to 55 years
  3. 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
  4. Evidence of progression of disease defined by an increase of ≥ 0.5 Expanded Disability Status Scale (EDSS) points in the last 12 months
  5. Disease duration 2 to 20 years (included)
  6. Expanded Disability Status Scale (EDSS) ≥ 6.5
  7. Presence of oligoclonal band in the cerebrospinal fluid (CSF) is required for Primary Progressive MS

Exclusion Criteria:

They will be excluded from the study patients:

  1. 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;
  2. treated with any immunosuppressive therapy, including but not limited to natalizumab and fingolimod, within the 3 months prior to screening;
  3. treated with interferon-beta or glatiramer acetate within the 30 days prior to screening;
  4. treated with corticosteroids within the 30 days prior to screening;
  5. if relapse occurred during the 30 days prior to screening;
  6. with contraindications for or intolerance to any medication, treatments and procedures that will be used in the study;
  7. 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;
  8. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03269071


Locations
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Italy
IRCCS Ospedale San Raffaele
Milan, MI, Italy, 20132
Sponsors and Collaborators
IRCCS San Raffaele
Fondazione Italiana Sclerosi Multipla
  Study Documents (Full-Text)

Documents provided by Gianvito MARTINO, IRCCS San Raffaele:

Publications of Results:
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Responsible Party: Gianvito MARTINO, Prof., IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT03269071     History of Changes
Other Study ID Numbers: 2016-002020-86 (EudraCT)
First Posted: August 31, 2017    Key Record Dates
Last Update Posted: February 26, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: It is not yet known the best way to exploit the Individual Participant data (IPD) that will become available

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gianvito MARTINO, IRCCS San Raffaele:
Multiple Sclerosis
Cell Therapy
Human Neural Stem Cells

Additional relevant MeSH terms:
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Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases