T Cell Vaccination in Patients With Progressive Multiple Sclerosis

NCT ID: NCT01448252

Last Updated: 2011-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-05-31
• Study Completion Date: 2009-03-31

Brief 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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TCV

multiple T cell vaccinations against nine myelin peptides at days 1, 30, 90, 180

Group Type: ACTIVE_COMPARATOR

T cell vaccination

Intervention Type: BIOLOGICAL

Multiple injections of autologous T cell lines reactive to 9 myelin peptides.

Placebo

saline injections subcutaneously at the same 4 time points with active treatment

Group Type: SHAM_COMPARATOR

multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides)

Intervention Type: BIOLOGICAL

multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides at days 1, 30,90,180

Interventions

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

Intervention Type: BIOLOGICAL

T cell vaccination

Multiple injections of autologous T cell lines reactive to 9 myelin peptides.

Intervention Type: BIOLOGICAL

Other Intervention Names

multiple subcutenous injections of saline at days 1, 30,90,180.

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

Dimitrios Karussis

Head, Multiple Sclerosis Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dimitrios Karussis, Prof.

Role: PRINCIPAL_INVESTIGATOR

Hadassah Medical Organizatin

Rivka Abulafia-Lapid, PhD

Role: STUDY_DIRECTOR

Hadassah Medical Organization

Locations

Dept of Neurology,Hadassah ein-Kerem

Jerusalem, , Israel

Countries

Israel

References

Karussis D, Shor H, Yachnin J, Lanxner N, Amiel M, Baruch K, Keren-Zur Y, Haviv O, Filippi M, Petrou P, Hajag S, Vourka-Karussis U, Vaknin-Dembinsky A, Khoury S, Abramsky O, Atlan H, Cohen IR, Abulafia-Lapid R. T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial. PLoS One. 2012;7(12):e50478. doi: 10.1371/journal.pone.0050478. Epub 2012 Dec 14.

Reference Type: DERIVED

PMID: 23272061 (View on PubMed)

Other Identifiers

27-15.15.00

Identifier Type: OTHER

Identifier Source: secondary_id

TCV-HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id