T Cell Vaccination in Patients With Progressive Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Autologous T Cell Vaccination With Line Specific for 9 Myelin Peptides in Patients With Progressive / Relapsing Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01448252
• Other study ID #: TCV-HMO-CTIL
• Secondary ID: 27-15.15.00
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 5, 2011
• Last updated: October 6, 2011
• Start date: May 2002
• Est. completion date: March 2009

Study information

• Verified date: October 2011
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2009
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Clinically definite MS (according to Poser's criteria) of the relapsing-progressive type (RPMS).

2. Age: 18-60.

3. EDSS: 3.0 to 7.0.

4. Disease duration: > 1 year.

5. Evidence of disease progression of 1 degree in the EDSS scale, or at least two severe relapses (requiring hospitalization and treatment) during the year prior to inclusion.

6. MRI of the brain with at least 5 lesions in the white matter (T2 imaging).

7. Failure to benefit from other existing treatments according to the guidelines of the Israeli Ministry of Health.

Exclusion Criteria:

1. Patients with other systemic active disease.

2. Patients who had been treated with immunosuppressive drugs during the 3-6 months depending on the cytotoxicity of the medication used prior to the inclusion.

3. Patients who previously received cellular immunotherapy or who are participating in other experimental protocols.

4. Pregnancy; Pregnant women or women who do not use efficacious contraception (oral contraception, or intra-uterine device).

5. Patients with an additional autoimmune condition unrelated to MS or significant allergy.

6. Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent, or in whom the clinician believes that a follow-up period of at least 12 months will not be possible.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides)
multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides at days 1, 30,90,180
• T cell vaccination
Multiple injections of autologous T cell lines reactive to 9 myelin peptides.

Locations

Country	Name	City	State
Israel	Dept of Neurology,Hadassah ein-Kerem	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EDSS changes	Follow up in changes in the EDSS score	one year	No
Primary	Relapse rate of MS	recording of the relapses of MS during the year of the study and the prior to the study	one year follow up	No
Primary	PASAT test	recording of the performance in the PASAT test during the one year of the study	one year	No
Primary	Nine hole PEG test	recording of the performance in the Nine hole PEG test test during the one year of the study	one year	No
Primary	timed ten meter walking	recording of the performance in the timed ten meter walking test during the one year of the study	one year	No
Secondary	Quantitative MRI evaluation	the burden of T2 lesions load, of the hypo-intense T1 lesions, of the Gadolinium enhancing lesions and of the brain atrophy will be evaluated at the end of the study and compared to the baseline values	one year	No