T Cell Vaccination in Patients With Progressive Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a double blind phase I-II clinical trial with multiple autologous T cell vaccinations
      using T cell lines reactive to 9 different myelin peptides of MBP, MOG and PLP, in patients
      with relapsing progressive Multiple Sclerosis.
    

Detailed description: 
      This trial is a phase I/II double-blind controlled clinical trial designed to evaluate the
      safety and clinical efficacy of multiple autologous T-cell vaccinations (on days 1, 30, 90
      and 180) in progressive MS patients which showed severe progression/deterioration in the
      functional status (at least, one degree in the EDSS scale) during the last year, or at least
      one severe relapse. The patients will be from our MS clinic and will be randomized (by
      computer) into two groups according to: age, disease duration, disease severity and
      progression rate. One group (2/3 of the patients) will receive the active treatment, i.e.
      TCV, and the other group (1/3 of the patients) will receive sham treatment (injection of
      sterile normal saline). The treating nurse, the treating physician, the examining neurologist
      (the one who will perform the neurological evaluation) and the patient will be blinded for
      the treatment.

      OBJECTIVES AND SIGNIFICANCE OF THE TRIAL

      A. To develop a new cell therapeutic modality for treating MS patients using attenuated
      autologous anti-MBP, anti-PLP and anti-MOG autoreactive T-cells as vaccines. The immune
      response induced by this vaccination will be directed specifically against the T-cells
      attacking the patient's nerve system (specifically the myelin sheath).

      B. To study and characterize these autoreactive T-cells in MS patients. The number and
      function of such cells in the course of the relapse of the disease, as well as during the
      periods of remissions, will be studied.

      C. To study the clinical efficacy of T-cell vaccination with attenuated anti-MBP and anti-MOG
      autologous T-cells on MS. The parameters to be examined will include: change in the
      disability status (by the EDSS disability scale, as well as by ambulation index and several
      other functional tests), the change in the relapse rate and in the timed 10-meters walking
      test, the PASAT test and the 9-hole peg test. MRI parameters will represent additional
      endpoints and will include: the changes in the total burden of the disease and in the
      quantity of irreversible damage (cortical atrophy and axonal loss). In addition, the effects
      of this treatment on the immune responses (i.e. number and proportion of activated
      lymphocytes, number and proportion of anti-myelin reactive lymphocytes in the peripheral
      blood and IgG antibody levels in the cerebrospinal fluid) will be evaluated in the treated MS
      patients.

      The significance and importance of the study are outlined as follows:

        1. It offers a new approach for the treatment of MS.

        2. This approach has the advantage of being devoid of toxic or general immunosuppressive
           effects.

        3. The study will pave the way for further studies that will improve our understanding of
           the mechanisms of the host immune response in MS and of the involvement of the MBP, PLP
           and MOG myelin proteins in the initiation of the auto-reactive immune response and of
           clinical MS.
    

Intervention name(s): multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides); T cell vaccination
Intervention type(s): Biological; Biological
Intervention description(s): multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides at days 1, 30,90,180; Multiple injections of autologous T cell lines reactive to 9 myelin peptides.
Other intervention name(s): multiple subcutenous injections of saline at days 1, 30,90,180.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: T cell vaccination; Immunotherapy; Tolerance; safety; clinical efficacy