Autologous T Cell Vaccination With Line Specific for 9 Myelin Peptides in Patients With Progressive / Relapsing Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- EDSS changes
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically definite MS (according to Poser's criteria) of the relapsing-progressive type (RPMS).
- •EDSS: 3.0 to 7.
- •Disease duration: > 1 year.
- •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.
- •MRI of the brain with at least 5 lesions in the white matter (T2 imaging).
- •Failure to benefit from other existing treatments according to the guidelines of the Israeli Ministry of Health.
排除标准
- •Patients with other systemic active disease.
- •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.
- •Patients who previously received cellular immunotherapy or who are participating in other experimental protocols.
- •Pregnancy; Pregnant women or women who do not use efficacious contraception (oral contraception, or intra-uterine device).
- •Patients with an additional autoimmune condition unrelated to MS or significant allergy.
- •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.
结局指标
主要结局
EDSS changes
时间窗: one year
Follow up in changes in the EDSS score
Relapse rate of MS
时间窗: one year follow up
recording of the relapses of MS during the year of the study and the prior to the study
PASAT test
时间窗: one year
recording of the performance in the PASAT test during the one year of the study
Nine hole PEG test
时间窗: one year
recording of the performance in the Nine hole PEG test test during the one year of the study
timed ten meter walking
时间窗: one year
recording of the performance in the timed ten meter walking test during the one year of the study
次要结局
- Quantitative MRI evaluation(one year)
研究者
Dimitrios Karussis
Head, Multiple Sclerosis Center
Hadassah Medical Organization