Phase IA Trial of Intrathecal Administration of Human Umbilical Cord Blood-Derived Cell Therapy (DUOC-01) in Adults With Primary Progressive Multiple Sclerosis (PPMS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of adverse events attributed to the investigational product
研究概览
简要总结
This study is a prospective Phase 1a open-label single- center trial. It will assess the safety of intrathecal administration of DUOC-01 cells to adults with Primary Progressive Multiple Sclerosis (PPMS). DUOC-01 is a population of cells expanded from donated human umbilical cord blood cells and is intended for treatment of neurodegenerative and demyelinating diseases. There will be approximately 20 participants enrolled. Exploratory objectives include changes in MS assessment scores, changes in brain MRI findings, and changes in blood biomarkers.
详细描述
This study is a prospective phase 1a open-label, single center trial. It is designed to assess the safety of administration of escalating doses of DUOC-01 intrathecally to adults with PPMS. DUOC-01 is a population of cells expanded from donated human umbilical cord blood mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+ monocytes. Based on pre-clinical rodent models, this cell product is considered a candidate for the treatment of injury-induced Central Nervous System (CNS) demyelination and modulation of neuroinflammation.
Approximately 20 participants will be enrolled. DUOC-01 will be infused into the cerebrospinal fluid (intrathecal infusion). The first 3 subjects will receive a single dose of 10 million cells (cohort 1). The next 3 subjects will receive a single intrathecal dose of >10 to 25 million cells (cohort 2), if manufacturing of this yield is reliable. The final 14 patients will receive a single intrathecal dose of >25 to 50 million cells (cohort 3), if manufacturing of this yield is reliable. Subjects will be followed for 12 months post administration.
Participants will be identified and screened for eligibility for the study. HLA typing will be performed on the participant, and once results become available, several >4/6 matched cord blood units (CBUs) will be selected from the Carolinas Cord Blood Bank (CCBB), an FDA licensed public cord blood bank at Duke University in Durham, NC. Cord blood units will have complete donor screening and testing per banking regulations.
The frozen CBU will be transferred to the GMP manufacturing facility at Duke University Medical Center per standard practice. Production, testing and release of DUOC-01 will take 19-21 days. Within 14 days prior to planned administration, subjects will receive a baseline brain MRI and be re-screened on MS assessments. Subjects will not be infused with DUOC-01 cells if they no longer meet inclusion criteria or if no qualifying DUOC-01 cells are available. If there is a failure of DUOC-01 manufacturing, a second cord blood unit, if available, will be utilized for repeat manufacturing.
DUOC-01 administration will occur by a trained clinician. A lumbar puncture (insertion of a needle into the lower back, into the cerebrospinal spinal fluid (CSF)) will be performed and baseline CSF samples will be obtained. The DUOC-01 product will be injected into the CSF (intrathecally) and appropriate monitoring will be performed.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects must be 18-65 years of age
- •Diagnosis of primary progressive MS according to 2017 revised McDonald criteria (26)
- •EDSS score at screening 3.0-6.5 that was not acquired within the last 6 months
- •Stable disease state as evidenced by no significant change in EDSS (1 point or more) in the last 3 months
- •Patients must have a suitably matched, banked UCB per section 5.3
- •Able to complete a written informed consent prior to any study assessments
- •Patients of childbearing potential must practice effective contraception during the study, and be willing to continue contraception for at least 6 months after DUOC-01 dosing so that, in the opinion of the Investigator, they will not become pregnant during the course of the study.
- •Patient is a good candidate for the trial, in the opinion of the Investigators
- •Subjects on disease-modifying therapies upon entering the study must continue on these therapies as a concomitant treatment throughout the course of the study to minimize additional variables. However, changes in these disease-modifying therapies can occur at the clinician's discretion, if there are clinical reasons to do so, which would be documented.
排除标准
- •1. Prior organ, tissue, or stem cell transplant or cell therapy within 3 years of study entry
- •Diagnosis of a progressive neurological disorder other than MS
- •Active, chronic disease of the immune system other than MS
- •Any medical condition that the investigator deems as unsuitable with therapy
- •Inability to have an MRI brain scan, or lumbar puncture (i.e., claustrophobia, allergy to contrast, bleeding disorder, or on anticoagulation)
- •Intractable seizures
- •Chronic aspiration
- •Bleeding disorder
- •Evidence of HIV infection or HIV positive serology
- •Uncontrolled bacterial, viral, or fungal infection within 2 weeks of DUOC-01 administration, as defined by progression while on appropriate treatment
- •History of malignancy of any organ system within the past two years with the exception of basal cell carcinoma or squamous cell carcinoma of the skin that has been excised with clear margins.
- •Requirement of ventilatory support
- •Pregnant or breastfeeding or intention to become pregnant during the study
- •Active concurrent malignancy, or receiving concurrent radiotherapy, immunosuppressive medications for conditions other than MS, or cytotoxic chemotherapy
- •Patients with Suicidal Ideation in the past 6 months per screening on C-SSRS; patients with Suicidal Behavior in the past 2 years, except for Non-suicidal self-injurious behavior
- •Abnormal lab values:
- •Total bilirubin>2.0 mg/dl unless due to Gilbert's syndrome
- •AST or ALT > 5 times the ULN
- •WBC <2.0x 103/μL
- •ALC <0.5 x 103/ μL
- •Serum creatinine >2x ULN
- •eGFR <60 mg/mmol
- •CD4 count <200 cells/mm3
研究组 & 干预措施
DUOC-01
Intrathecal Infusion of DUOC-01 and hydrocortisone. Cohort 1: 10 million cells Cohort 2: greater than 10 to 25 million cells Cohort 3: greater than 25 to 50 million cells
干预措施: DUOC-01 (Biological)
结局指标
主要结局
Incidence of adverse events attributed to the investigational product
时间窗: 1 year post infusion
Cumulative summary of adverse events related to DUOC-01
Incidence of IT administration adverse events
时间窗: 2 weeks post infusion
Total number of adverse events associated with DUOC-01 infusion
次要结局
未报告次要终点
研究者
Joanne Kurtzberg, MD
Professor of Pediatrics
Duke University