A "negative"dendritic Cell-based Vaccine for the Treatment of Multiple Sclerosis: a First-in-human Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Safety (Occurrence and severity of adverse events will be recorded)
研究概览
简要总结
A first-in-human clinical trial to treat patients with multiple sclerosis by vaccination with tolerogenic dendritic cells (tolDC), generated using Good Manufacturing Practice (GMP) will be conducted. In doing so, the feasibility and safety of administering myelin-derived peptide-pulsed tolDC in patients with MS will be assessed.
详细描述
A phase I dose-escalating clinical trial will be conducted in a coordinated and comprehensive manner to determine safety and tolerability, and to enable selection of a suitable dose regimen for phase II trials. The primary objective of the phase I study will be to determine whether tolDC-based therapy is safe and well tolerated and to establish the dose-response, with clinical relapse rates, neurological disability (assessed using various scales) and MRI endpoints, measured over 12 months. Patients will serve as their own controls pre- and post-vaccination. Completion of screening assessments and confirmation of eligibility criteria should take no longer than 6 weeks. First-line treatments will be stopped 6 weeks before baseline at the latest.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •MS according to 2010 revised McDonald criteria (76);
- •Expanded disability status scale (EDSS) of 0-6.5 inclusive;
- •Disease duration of maximum 15 years and first signs or symptoms at least 6 months prior to enrolment in the study;
- •Active MS (relapsing and progressive): -1 relapse in the past year and/or
- •at least 1 enhancing lesion on brain MRI in the past year
- •new or enlarging T2 lesion(s) in comparison with a reference scan from maximum 1 year before
- •Neurologically stable with no evidence of relapse for at least 30 days prior to start of screening and throughout during the screening phase;
- •Positive T cell reactivity response to a mix of 7 myelin-derived peptides;
- •Able to sign informed consent;
- •Ability to comply with the protocol assessments;
- •Appropriate venous access.
- •Use of adequate contraceptive measures
排除标准
- •Previous use of immunosuppressive or cytostatic treatment, including mitoxantrone, alemtuzumab or bone marrow transplantation or stem cell transplantation at any time prior to enrolment;
- •Treatment with fingolimod or natalizumab or dimethylfumarate or teriflunomide within the last 3 months prior to study enrolment;
- •Pregnancy or planning pregnancy in the next 12 months and breast feeding;
- •Drug or alcohol abuse;
- •Inability to undergo MRI assessments;
- •History of or actual signs of immunodeficiency or malignancies;
- •Concurrent clinically relevant cardiac, immunological, pulmonary, neurological, renal or other major disease;
- •Hepatitis B, C, HIV, Syphilis or tuberculosis
- •Splenectomy;
- •Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that could interfere with the compliance to the protocol.
研究组 & 干预措施
tolerogenic dendritic cells (tolDC)
Each vaccine (5x106, 10x106 , or 15x106cells in 500 µL NaCl 0.9% solution supplemented with 5% human albumin) will be administered through intradermal injection at 5 sites (100 µL/site) in the subclavicular region (5-10 cm from the cervical lymph nodes). Injection sites will alternate between left and right sides.
干预措施: tolerogenic dendritic cells (tolDC) (Biological)
结局指标
主要结局
Safety (Occurrence and severity of adverse events will be recorded)
时间窗: 6 months
Occurrence and severity of adverse events will be recorded
Feasibility (Generation of GMP-grade cell product released according to QC)
时间窗: 6 months
Generation of GMP-grade cell product released according to QC
次要结局
- 9 Hole Peg Test (9HPT)(6 months)
- Symbol Digit Modalities test (SDMT)(6 months)
- Number of Gd-enhancing lesions on MRI(6 months)
- Number of new or enlarging T2 lesions on MRI(6 months)
- Expanded disability status scale (EDSS)(6 months)
- 25 Foot walk test (T25FW)(6 months)
研究者
Zwi Berneman
Professor
University Hospital, Antwerp