Phase 1/2 Clinical Trial With Autologous Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- To assess the safety of IV therapy with autologous Mesenchymal Stem Cells (MSCs) in MS patients.
研究概览
简要总结
The aim of the study is to evaluate the safety and efficacy of autologous mesenchymal stromal cells as treatment for Multiple Sclerosis.
详细描述
MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18-50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2-15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5-6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of MS
- •a. Relapsing remitting MS (RRMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by one or more of the following: i. ≥1 clinically documented relapse in past 12 months ii. ≥2 clinically documented relapses in last 24 months iii. ≥1 GEL at MRI performed within the last 12 months
- •b. Secondary progressive MS (SPMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by both: i. an increase of ≥1 EDSS point (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥ 5.5) in the last 12 months ii. ≥1 clinically documented relapse or ≥ 1 GEL at MRI within the last twelve months.
- •c. Primary progressive MS (PPMS) patients with all the following features: i. an increase of ≥1 EDSS point (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥5.5), in the last twelve months ii. ≥ 1 GEL at MRI performed within the last 12 months iii. positive cerebrospinal fluid (CSF) (oligoclonal banding)
- •Age 18 to 50 years
- •Disease duration 2 to 10 years (included)
- •EDSS 3.0 to 6.5
排除标准
- •RRMS not fulfilling inclusion criteria
- •SPMS not fulfilling inclusion criteria
- •PPMS not fulfilling inclusion criteria
- •Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or Hepatitis C
- •Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
- •Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization
- •Treatment with corticosteroids within the 30 days prior to randomization
- •Relapse occurred during the 60 days prior to randomization
- •Previous history of a malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year
- •Severely limited life expectancy by another co-morbid illness
- •History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts
- •Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study)
- •eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination.
- •Inability to give written informed consent in accordance with research ethics board guidelines
结局指标
主要结局
To assess the safety of IV therapy with autologous Mesenchymal Stem Cells (MSCs) in MS patients.
时间窗: 48 weeks
The primary objective of the study is to assess the safety of IV therapy with autologous MSCs in MS. Number of participants with adverse events will be documented at week 0,4,8,12,16,20,24,28,32,36,40,44,48 post treatment. Co-primary objective of the study is to evaluate the activity of autologous MSCS in MS patients, in terms of reduction as compared to placebo in the total number of contrast-enhancing lesions (GEL) at MRI acquired on conventional 1,5 T MRI scans over 24 weeks.
次要结局
- To gather preliminary information of the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).(48 weeks)
研究者
Lou Brundin
MD, PhD
Karolinska Institutet