Tolerance-Induction With Dendritic Cells Treated With Vitamin-D3 and Loaded With Myelin Peptides, in Multiple Sclerosis Patients (TOLERVIT-MS)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Neurologic changes
研究概览
简要总结
The purpose of this study is to determine the safety and tolerability of the intranodal administration of autologous monocyte-derived dendritic cells tolerised with Vitamin-D3 and pulsed with myelin peptides (tolDC-VitD3) in multiple sclerosis patients . To select the most appropriate regime for the development of future therapeutic trials.
To evaluate the preliminary proof of concept by clinical and/or radiological activity and immunological markers.
详细描述
Phase I dose ascending ("best of five") clinical trial.
First group will start by intranodal injection in cervical lymph nodes of 5*10^6 tolDC-VitD3.
Up titration depending on security outcomes to 10*10^6 tolDC-VitD3, same route in second cohort dose and next uptitration to 15*10^6 tolDC-VitD3.
Six cycles per patient with the following schema: for the first four cycles the administration will be each 2 weeks, for the remaining 2 cycles administration each 4 weeks.
A last cohort with the dose identified in the previous groups, administered in patients treated with beta interferon, same route, same dose schema.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •EDSS of 0.0 - 6.
- •Multiple Sclerosis according to 2010 revised Mc Donald criteria, and less than 15 years of evolution of disease.
- •Patients with:
- •Active relapsing remitting multiple sclerosis (RRMS) (more than 1 relapse in last year and/or occurrence of ≥3 new T2 lesions or Gd positive) who not wish to be treated with current therapies.
- •Low activity RRMS (1 relapse in last year or occurrence of 1 or 2 T2 lesions or Gd positive) without treatment.
- •Progressive forms of MS with activity (at least 1 relapse in last year or occurrence 1 or 2 T2 lesions or Gd positive).
- •RRMS treated with interferon beta (Additional group)
- •T cell proliferation to the pool of myelin peptides against which is to induce immune tolerance: Myelin basic protein (MBP)13-32, MBP83-99, MBP111-129, MBP146-170, proteolipid protein (PLP) 139-154, Myelin oligodendrocyte glycoprotein (MOG)1-20, MOG35 -55).
- •Adequate peripheral venous access.
- •Signed informed consent.
排除标准
- •Use of corticosteroids during the prior 4 weeks.
- •Use of interferon beta -in patients who is retired by inefficiency or other causes- and glatiramer acetate in the 4 weeks prior.
- •Use of fingolimod, dimethylfumarate, natalizumab, immunoglobulins or plasmapheresis at 12 weeks; and teriflunomide in the 15 weeks prior.
- •Use of azathioprine, mitoxantrone, rituximab, methotrexate, cyclophosphamide, cyclosporine, alemtuzumab or other immunosuppressive drug, except corticosteroids, at any time.
- •Bone marrow or stem cell transplant at any time.
- •Relapse during the month prior of starting treatment. If it appears and the patient meets the eligibility criteria, must wait long enough until the end of the 30 days free of relapse. If corticosteroids are administered, the MRI performed during this period should not be considered, and a new MRI will be performed at 4 weeks after administration of corticosteroids.
- •Pregnancy or planning pregnancy within the next 12 months and breastfeeding.
- •Fertile patients who are not using an appropriate method of contraception. If the patient is menopausal or sterile it must be documented in the medical record.
- •Abusing drugs or alcohol.
- •Inability to undergo MRI evaluations.
- •Seropositivity for HIV, hepatitis B or C and/or syphilis.
- •History of oncological disease.
- •Clinically relevant concomitant disease: cardiac, pulmonary, neurological, renal or other major illness.
- •Splenectomy.
- •Dementia, psychiatric problems or other comorbidities that might interfere protocol compliance.
- •To be participating in another clinical study or to have participated in one in the last 3 months.
研究组 & 干预措施
5 * 10 ^6 tolDC-VitD3
5 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)
干预措施: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) (Drug)
10 * 10 ^6 tolDC-VitD3
10 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3).
干预措施: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) (Drug)
15 * 10 ^6 tolDC-VitD3
15 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3).
干预措施: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) (Drug)
Interferon-beta
Additional group (patients treated with beta-interferon) will receive the selected dose of those 3 previously cohorts studied
干预措施: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) (Drug)
Interferon-beta
Additional group (patients treated with beta-interferon) will receive the selected dose of those 3 previously cohorts studied
干预措施: Interferon-beta (Drug)
结局指标
主要结局
Neurologic changes
时间窗: 24 months
New relapse. Disability progression on Expanded Disability Status Scale (EDSS)
Safety as assessed by the occurrence and severity of adverse events
时间窗: 24 months
Occurence and severity of adverse events will be recorded
Radiologic changes
时间窗: 24 months
Number of new or enlarging T2 lesions on brain MRI. Number of Gadolinium (Gd)-enhancing T1 lesions on brain MRI
次要结局
- Annual relapse rate (ARR)(24 months)
- Symbol Digit Modalities Test (SDMT)(24 months)
- Lymphocyte proliferation to myelin peptides(24 months)
- Blood Immunomonitoring studies(24 months)
- Expanded Disability Status Scale (EDSS)(24 months)
- Radiologic preliminary efficacy(24 months)
- 9-Hole Peg Test (9HPT)(24 months)
- Feasibility(6 months)
- 25-Foot Walking Test (T25FW)(24 months)