Neural Stem Cell Transplantation in Multiple Sclerosis Patients
Condition: Progressive Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
Study type: Interventional
Phase: Phase 1

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
    

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.
    

Intervention name(s): human fetal-derived Neural Stem Cells (hNSCs)
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): human Neural Stem Cells (hNCSs)
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple Sclerosis; Cell Therapy; Human Neural Stem Cells