Allogenic Adipose Tissue-derived Mesenchymal Stromal Cells for the Treatment of Primary Progressive Multiple Sclerosis: an Open-label Phase I Clinical Trial.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Percentage of patients experiencing at least one adverse effect
研究概览
简要总结
In this study, we propose, for the first time, to test the safety and the potential efficacy of repeated allogenic Adipose tissue-derived Mesenchymal Stromal Cells IT injections in Primary Progressive Multiple Sclerosis patients.
详细描述
In this study, the investigators propose, for the first time, to test the safety and the potential efficacy of repeated allogenic Adipose tissue-derived Mesenchymal Stromal Cells (ASCs) IT injections in Primary Progressive Multiple Sclerosis (PPMS) patients. In fact, even if autologous Bone Marrow-Mesenchymal Stromal Cells (BM-MSC) and ASCs have already been infused intrathecally in multiple sclerosis, repeated injections of allogenic ASCs have never been tested in this disease. The use of allogenic cells is driven by recent publications reporting decreased suppressive properties of autologous MSC from MS patients.
The hypothesis is that 3 repeated intrathecal (IT) injections of allogenic ASCs every 3 months will be safe and can lower disease progression in PPMS patients.
Preamble of infusing ASCs in the first patient, it's necessary to constitute and characterize the ASC bank. ASC will be obtained from Allogeneic human mesenchymal stromal cells derived from adipose tissue of a living donor.
Once the bank is available, MS patients will be screened and included in Rennes university hospital to received ASC's infusions.
MS patients will be followed for one year after inclusion
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with Primary Progressive MS according to the criteria of Mc Donald 2017 (Thompson et al Lancet neurol, 2017)
- •Age between 18 and 55 years
- •EDSS score: 3 to 6 at inclusion
- •Documented evidence of disability progression independent of relapse activity at any point in time over the 2 years prior to the screening visit
- •Positive CSF with oligoclonal bands
- •For women of childbearing potential (WOCBP), effective contraception as per the CFTG recommendations (version 1.1)
- •Having signed a free, informed and written consent
- •Affiliated to social security scheme
排除标准
- •Inflammatory activity during the past year (relapses or new T2 MRI lesions)
- •Disease Modifying Drugs during the past year
- •Treatment with high dose corticosteroids during the 30 days preceding the inclusion
- •Contra indication to lumbar puncture/intrathecal infusion: intracranial hypertension, puncture site infections, severe thrombocytopenia (<50 G/L), anticoagulant or fibrinolytic treatment
- •Participation in another therapeutic trial in the last 6 months
- •Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of their liberty, pregnant or breastfeeding women, minors, persons unable to express their consent
研究组 & 干预措施
Patient
repeated allogenic ASCs IT injections
干预措施: Adipose tissue-derived Mesenchymal Stromal Cells (Drug)
结局指标
主要结局
Percentage of patients experiencing at least one adverse effect
时间窗: 48 weeks
Percentage of patients experiencing at least one adverse effect (AE) due to ASC infusion qualified as CTCAE V5 grade ≥ 3 or qualified as "serious" AE using the MeDRA terminology, and occurring between the first infusion and the end of the follow-up. The severity of the AE and the causality of the ASC infusion will be validated by a DSMB
次要结局
- Description of Adverse events related to experimental product(48 weeks)
- Clinical disease evolution at Week24 and Week48 after treatment : Confirmed Disability Progression using Expanded Disability Status Scale score(3 months)
- Clinical disease evolution at Week24 and Week48 after treatment : no evidence progression using 9HPT test(48 weeks)
- Clinical disease evolution at Week24 and Week48 after treatment : no evidence progression using T25-FW(48 weeks)
- Clinical disease evolution at Week24 and Week48 after treatment : MSFC mean changes(48 weeks)
- Quality of life disease evolution at Week24 and Week48 after treatment : Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire(48 weeks)
- Immunophenotyping(48 weeks)
- Detection of donor specific anti-HLA antibodies in the blood(28 weeks)
- MRI parameters : gadolinium (Gd) enhancing lesions(48 weeks)
- MRI parameters : new T2 lesions(48 weeks)
- MRI parameters : change in brain volume(48 weeks)
- MRI parameters : change in spinal cord volume(48 weeks)
- Clinical disease evolution at Week24 and Week48 after treatment : Expanded Disability Status Scale score(48 weeks)