Neural Stem Cell Transplantation in Multiple Sclerosis Patient: a Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- SHORT TERM (0-24 hours) Overall survival
研究概览
简要总结
This is a phase I study evaluating the feasibility, safety and tolerability of intrathecally administered human Neural Stem Cells (hNSCs), at an escalating dose ranging from 0.7x10^6±10% cells to 5.7x10^6±10% cells/kg of body weight, in patients affected by Progressive Multiple Sclerosis
详细描述
This is a prospective, monocentric, national, therapeutic exploratory, phase I, not randomized, open label, not controlled, single dose escalation clinical trial.
Each subject will participate in the study for approximately 96 weeks. Participation will include a screening evaluation between -28 and -7 days before the Advance Therapy Investigational Medicinal Products (ATIMP) administration.
A follow-up with clinical visits will be performed from 1 to 96 weeks.
The protocol will consist of a total of four treatment cohorts (TCs), labeled from A to D, each receiving a single escalating dose of allogenic fetal-derived human Neural Stem Cells (hNSCs) injected intrathecally, as it follows:
- TC-A: 0.7x10^6 ± 10% cells/kg of body weight;
- TC-B: 1.4x10^6 ± 10% cells/kg of body weight;
- TC-C: 2.8x10^6 ± 10% cells/kg of body weight;
- TC-D: 5.7x10^6 ± 10% cells/kg of body weight.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Signature of the informed consent by the patient or patients' legal tutors
- •Age 18 to 55 years
- •Diagnosis of a. Progressive MS as per the revised MC Donald 2010 criteria with a progressive course according to 2013 Lublin phenotypes classification (PMS) with failure or intolerance to all approved therapies according to the disease course or without any alternative approved therapy
- •Evidence of progression of disease defined by an increase of ≥ 0.5 Expanded Disability Status Scale (EDSS) points in the last 12 months
- •Disease duration 2 to 20 years (included)
- •Expanded Disability Status Scale (EDSS) ≥ 6.5
- •Presence of oligoclonal band in the cerebrospinal fluid (CSF) is required for Primary Progressive MS
排除标准
- •They will be excluded from the study patients:
- •with any active or chronic infection or diseases other than MS including but not limited to infection with HIV1-2, Hepatitis B or Hepatitis C and tuberculosis or immune deficiency syndromes;
- •treated with any immunosuppressive therapy, including but not limited to natalizumab and fingolimod, within the 3 months prior to screening;
- •treated with interferon-beta or glatiramer acetate within the 30 days prior to screening;
- •treated with corticosteroids within the 30 days prior to screening;
- •if relapse occurred during the 30 days prior to screening;
- •with contraindications for or intolerance to any medication, treatments and procedures that will be used in the study;
- •pregnant or in lactation or of childbearing age who are not willing to use a contraceptive method effective* for the entire duration of the study;
- •who, in the opinion of the investigator, showing any condition that would preclude study participation.
- •refer to guideline http://www.hma.eu/fileadmin/dateien/Human_Medicines/01 About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf
研究组 & 干预措施
Treatment Cohort A
See Study Description
TC-A: 0.7 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
干预措施: human fetal-derived Neural Stem Cells (hNSCs) (Drug)
Treatment Cohort B
See Study Description
TC-B: 1.4 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
干预措施: human fetal-derived Neural Stem Cells (hNSCs) (Drug)
Treatment Cohort C
See Study Description
TC-C: 2.8 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
干预措施: human fetal-derived Neural Stem Cells (hNSCs) (Drug)
Treatment Cohort D
See Study Description
TC-D: 5.7 x 10^6 ± 10% human fetal-derived Neural Stem Cells (hNSCs) / kg of body weight
干预措施: human fetal-derived Neural Stem Cells (hNSCs) (Drug)
结局指标
主要结局
SHORT TERM (0-24 hours) Overall survival
时间窗: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of patients alive all over the trial
SHORT TERM (0-24 hours) Overall safety and tolerability measured by Adverse Event (AE) recording
时间窗: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of AEs in alive patients all over the trial
SHORT TERM (0-24 hours) Changes in neurological conditions not related to disease
时间窗: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of changes in neurological conditions not related to disease of alive patients all over the trial
SHORT TERM (0-24 hours) Proportion of successful intrathecal administration procedure (feasibility)
时间窗: 0-24 hours after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of successful intrathecal administration procedures versus all intrathecal administration procedures in the whole trial
MID TERM (day 1- day 14) Overall survival
时间窗: from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of alive patients in the whole trial
MID TERM (day 1- day 14) Overall safety and tolerability measured by AE recording
时间窗: from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of AEs of alive patients in the whole trial
MID TERM (day 1- day 14) Changes in neurological conditions not related to disease
时间窗: from 1 to 14 days after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of changes in neurological conditions not related to disease in alive patients of the whole trial
LONG TERM (day 15 - week 96) Overall survival
时间窗: from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of alive patients in the whole trial
LONG TERM (day 15 - week 96) Overall safety and tolerability measured by AE recording
时间窗: from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of AEs in alive patients of the whole trial
Long term incidence of malignancies
时间窗: from day 0 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
Incidence of malignancies in alive patients of the whole trial
Evaluation of changes in quality of life measures
时间窗: 12, 24, 48, 72 and 96 weeks
Health-related quality of life will be assessed by standardized questionnaires
LONG TERM (day 15 - week 96) Changes in neurological conditions not related to the disease
时间窗: from day 15 to week 96 after intrathecal injection of human Neural Stem Cells (hNSCs)
Number of changes in the neurological conditions not related to disease in alive patients of the whole trial
次要结局
未报告次要终点
研究者
Gianvito MARTINO
Prof.
IRCCS San Raffaele