An Open-label, Non-randomized, Phase I/II Study of Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and Liberation Therapy (When Associated With Chronic Cerebrovascular Venous Insufficiency) in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Proportion of patients with clinical improvement in EDSS score compared to baseline
研究概览
简要总结
STUDY OBJECTIVES:
Primary Objective: Assessment of treatment safety based on incidence of any treatment emergent/treatment associated adverse events prior to discharge and at 1, 3, 6 and 12 months post treatment.
Secondary objective: Assessment of efficacy at baseline, prior to discharge, 1 month, 3 months, 6 months and 12 months after treatment based on the following: EDSS and 29-item Multiple Sclerosis Impact Scale (MSIS-29), MS Functional Composite (MSFC) consisting of (1) Timed 25-Foot Walk, (2) 9 Hole Peg Test, and (3) Paced Auditory Serial Addition Test and gadolinium-enhanced magnetic resonance imaging (MRI)
详细描述
STUDY TREATMENT:
Investigational therapy product: Wharton Jelly derived allogeneic MSCs.
Method of administration and dose: Super selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs in dose of 100 million along with liberation therapy (when associated with CCSVI).
SAFETY AND EFFICACY EVALUATION:
The proposed study will assess safety and primary and secondary efficacy endpoints after super selective intravenous and intrathecal administration of allogeneic umbilical cord mesenchymal stem cells (UC-MSC) in 69 patients with Relapsing Remitting Multiple Sclerosis.
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
- •Main inclusion criteria: Males and Females between age 18 and 60 years with confirmed diagnosis of Relapsing Remitting Multiple Sclerosis made by a neurology expert/MS expert with lesions demonstrated on brain MRI that are consistent with MS and having an EDSS (Kurtzke Expanded Disability Status Scale) score between 3.5 & 6
- •Inclusion Criteria:
- •Males and Females between age 18 and 60 years
- •Diagnosis of Relapsing Remitting Multiple Sclerosis made by a neurology expert/MS expert with lesions demonstrated on brain MRI that are consistent with MS
- •Duration of disease: >5 years
- •Having an EDSS (Kurtzke Expanded Disability Status Scale) score between 3.5 & 6
- •History of 2 or more relapses within last 2 years with increase in EDSS scale of > 0.5 sustained for > 4 weeks
- •Failure to respond or intolerance to the currently available Multiple Sclerosis (MS) immunomodulatory treatments): the lack of response to these treatments will be determined/defined by history of 2 or more relapses within last 2 years with increase in EDSS scale of > 0.5 sustained for > 4 weeks
- •Must have proof of health insurance in country of residence
排除标准
- •Primary progressive, secondary progressive or progressive relapsing MS as defined by Lublin and Reingold,
- •These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapses but are distinguished from relapsing remitting subjects by the lack of clinically stable periods of clinical improvement.
- •Unable to perform Timed 25-Foot Walk, 9 Hole Peg Test (HPT) (with both upper extremities) and Paced Auditory Serial Addition Test (PASAT 3)
- •Females who are pregnant or nursing or females of childbearing potential who are unwilling to maintain contraceptive therapy for the duration of the study
- •Life expectancy < 6 months due to concomitant illnesses
- •Exposure to any investigational drug or procedure within 1 month prior to study entry or enrolled in a concurrent study that may confound results of this study.
- •Active infectious disease: For patients who have tested positive, an expert will be consulted as to patient eligibility based on the patient's infectious status
- •Any illness which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results
- •Patients on chronic immunosuppressive transplant therapy
- •Patients with unstable cardiac status (unstable angina, attack of myocardial infarction within last 6 months, uncontrolled high blood pressure, hypotension, cardiomyopathy)
- •Cerebrovascular accident within 6 months prior to study entry
- •Patients with poorly controlled diabetes mellitus
- •Patients with renal insufficiency (Creatinine> 2.5) or failure
- •Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or who in the opinion of the investigator is not suitable to participate.
- •History of cancer (other than non-melanoma skin cancer or in-situ cervical cancer) in the last five years
- •Unwilling and/or not able to give written informed consent.
结局指标
主要结局
Proportion of patients with clinical improvement in EDSS score compared to baseline
时间窗: Up to 12 months
Proportion of patients with clinical improvement in EDSS score compared to baseline. Clinical improvement is defined as decrease in Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline.
次要结局
- Proportion of patients with a change in mobility and leg function as measured by the 25 foot walking test(12 months)
- Proportion of patients with a change in either gadolinium enhancing or new T2-weighted lesions on brain MRI(12 months)
- Proportion of patients with reduction in brain volume on MRI(12 months)
- Proportion of patients with reduction in T2 lesion volume on brain MRI(12 months)
- Proportion of patients with clinical improvement in EDSS score compared to baseline(3 months and 6 months)
- Proportion of patients with clinical improvement in MSFC score compared to baseline(3 months, 6 months and 12 months)
- Proportion of patients with a change in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT)(12 months)
- Proportion of patients with reduced number of relapses or freedom from progression of disease(3 months, 6 months and 12 months)
- Proportion of patients with clinical improvement in MSIS score compared to baseline(3 months, 6 months and 12 months)
- Proportion of patients with a change in upper extremity function as measured by the Nine Hole Peg Test(12 months)