Neural Stem Cell Transplantation in Multiple Sclerosis Patients (STEMS)

September 2, 2021 updated by: Gianvito MARTINO, IRCCS San Raffaele

Neural Stem Cell Transplantation in Multiple Sclerosis Patient: a Phase I Study

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • MI
      • Milan, MI, Italy, 20132
        • IRCCS Ospedale San Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • human Neural Stem Cells (hNCSs)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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
Time Frame: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
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
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
0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
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
0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
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
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
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
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
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
from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)
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
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
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
from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
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
from day 0 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
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, 24, 48, 72 and 96 weeks
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
from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS San Raffaele

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fondazione Italiana Sclerosi Multipla

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gianvito Martino, IRCCS San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 17, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 31, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 5, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2016-002020-86 (EudraCT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

It is not yet known the best way to exploit the Individual Participant data (IPD) that will become available

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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