STEM-PD Trial: A Multicentre, Single Arm, First in Human, Dose-escalation Trial, Investigating the Safety and Tolerability of Intraputamenal Transplantation of Human Embryonic Stem Cell Derived Dopaminergic Cells for Parkinson's Disease (STEM-PD Product)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Region Skane
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- The number and nature of adverse events and serious adverse events in the first 12 months following transplantation
研究概览
简要总结
Parkinson's disease (PD) occurs when an area of the brain begins to lose nerve cells that produce a chemical called dopamine. Dopamine is an important chemical, and one of its functions is that it helps to regulate body movement. The loss of these nerve cells leads to a reduction of dopamine in the brain. Medications used to treat PD temporarily replace this lost dopamine, but they do not repair the underlying disease. One of the most promising PD therapies to date has been the transplantation of dopamine producing cells into the brain. Unlike current treatments, these therapies may be able to repair the damage caused in PD.
In this trial, the investigators will transplant a new stem cell therapy, called the STEM-PD product, into the area of the brain affected in people with PD. These stem cells can develop into many different cell types, including dopamine-producing nerve cells. The investigators will transplant the stem cells using a device that has been previously used for similar transplants in Lund. This is the first time that the STEM-PD product will be given to humans.
The trial aims to assess whether the STEM-PD product is safe to use in people with PD. The investigators will also be looking for preliminary signs of efficacy.
The trial will recruit participants with PD from the UK and Sweden. Eight participants will undergo the STEM-PD product transplant. Participants will receive a single dose of the STEM-PD product. Participants will attend for 25 visits primarily at their local recruiting hospital. For participants from the UK, some of the imaging will be performed at Invicro (London), and the surgery (including some visits before and after) and some imaging will be performed in Lund. All participants will be followed up for 36 months following surgery
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
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have given written informed consent to participate in the trial
- •Diagnosed with PD as defined using Queens Square Brain Bank criteria
- •Moderate disease as defined by having Hoehn and Yahr stage 2-3 in OFF state
- •Disease duration > 10 years
- •Male or female, aged between 50 and 75 years (inclusive)
- •Have a significant response to dopamine therapies as judged by the PI or other delegated clinician
- •Have symptoms that are not appropriately controlled by existing oral anti-PD medications, as judged by the PI or other delegated clinician
- •Ability to travel to Lund for surgery
- •Followed up for at least 12 months prior to inclusion in this trial in the TransEUro observational study
- •Be fluent in English/Swedish to enable completion of questionnaires as assessed by the PI or other delegated clinician at Cambridge/Lund, respectively
- •Be approved by the TMG clinical sub-group for trial participation
排除标准
- •Tremor dominant disease, as assessed by the PI or other delegated clinician
- •Significant drug induced dyskinesias as defined by a score of > 2 in the Abnormal Involuntary Movement Scale (AIMS) dyskinesias rating scale, in any body part in the ON state
- •Ongoing major medical or psychiatric disorders, including depression (MADRS > 20) and psychosis, that make participation unsuitable, as judged by the PI or other delegated clinician
- •Any contraindication to neurosurgery
- •Unable to be imaged using MRI
- •Extensive ventral striatal loss or normal findings on F-DOPA PET at screening
- •Significant cognitive impairment indicative of an incipient dementia/established dementia or values consistent with MoCA score of ≤ 24
- •Unable to perform normal copying of interlocking pentagons and/or a semantic fluency score for naming animals of less than 20 over 90 seconds
- •Other concomitant treatment with neuroleptics (including atypical neuroleptics) and/or cholinesterase inhibitors
- •Previous neurosurgery to the brain, or cell or organ transplantation, or recipient of repeated blood transfusions
- •Any contraindication to immunosuppressive therapy, prophylactic antibiotics, and/or osteoporosis prophylaxis (refer to STEM-PD Trial Immunosuppressant Manual)
- •High levels of pre-formed specific anti-HLA antibodies to the cell product
- •Severely reduced TPMT activity (less than half of the lower normal TPMT activity level)
- •History of documented severe/significant allergy requiring treatment
- •Female who is pregnant or breastfeeding
- •Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks of the screening visit, or is currently enrolled in an interventional investigational trial
- •Female of childbearing potential or male unwilling to follow contraception requirements (see protocol section 12.15)
- •Any other condition which, in the opinion of the investigator, makes the patient inappropriate for entry into the trial
研究组 & 干预措施
Dose 1
The starting dose of this trial is selected as a dose of cells that is likely to be the minimal therapeutic dose, i.e. 100,000 surviving DA neurons per putamen, obtained by transplanting 3.54 million STEM-PD cells per putamen.
干预措施: STEM-PD (Biological)
Dose 2
To ensure that the investigators are not using a potentially suboptimal cell dose, the investigators also plan to test a higher dose, which is double the dose of dose 1, i.e., 200,000 surviving DA neurons (= 7.08 million transplanted STEM-PD cells) per putamen.
The Data and Safety Monitoring Board (DSMB) for the trial will make a recommendation for the dosing once participants 1-4 have been dosed and data is available for imaging and clinical measurements, as well as safety reports, 6 months after the last patient has been grafted. The DSMB can recommend either to: i) remain at dose 1; ii) proceed to dose 2; or, iii) wait longer to collect more data. The final decision will be made by the clinical sub-group of the Trial Management Group, after receiving confirmation of the DSMB's recommendation.
干预措施: STEM-PD (Biological)
结局指标
主要结局
The number and nature of adverse events and serious adverse events in the first 12 months following transplantation
时间窗: 12 months following transplantation
Adverse events are recorded from the point of participant informed consent and at every trial visit
Absence of space occupying masses on cranial MRI in the first 12 months following transplantation
时间窗: 12 months following transplantation
Magnetic resonance imaging (MRI) scans
次要结局
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using semantic (animal naming) fluency(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using the stroop test(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using the Wechsler Adult Intelligence Scale (WAIS) similarities test(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using the Montreal Cognitive Assessment (MoCA)(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; changes in non-motor and QOL assessments using the EuroQol five-dimension, 5 level scale (EQ-5D-5L)(36 months following transplantation)
- Change in anti-Parkinson medication as measured by change L-dopa equivalent dose(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; changes in non-motor and QOL assessments using the Parkinson's Disease Questionnaire 39 (PDQ-39)(36 months following transplantation)
- Changes in motor features in the OFF state using the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS)(36 months following transplantation)
- Changes in motor features in the OFF state using a challenge test of levodopa(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; emergence of new neurological features,(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using the Boston naming task.(36 months following transplantation)
- Changes in motor features in the OFF state using the nine-hole peg test(36 months following transplantation)
- Changes in motor features in the OFF state using the timed sit-stand-walk test(36 months following transplantation)
- Changes in motor features in the OFF state using the Hauser patient diary card(36 months following transplantation)
- Changes in motor features in the OFF state using Parkinson KinetiGraph® (PKG®)(36 months following transplantation)
- The number and nature of SAEs and AEs in the 12 to 36 months period following transplantation(12 to 36 months period following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using the Hopkins verbal learning task-revised (HVLT-R)(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using the Digit Span test.(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; changes in non-motor and QOL assessments using the PD non motor symptom scale (NMSS).(36 months following transplantation)
- Changes in motor features in the OFF state using the Abnormal Involuntary Movement Scale (AIMS)(36 months following transplantation)
- Changes in motor features in the OFF state using the 30 second tap test(36 months following transplantation)
- Changes in clinical effects at 36 months following transplantation compared to baseline; global cognitive changes assessed using the pentagon copying test(36 months following transplantation)
- Changes in motor features in the OFF state using the RUSH dyskinesia scale(36 months following transplantation)
- Changes in F-DOPA uptake and dopamine transporter (DAT) binding at 36 months on PET imaging with F-DOPA and PE2i compared to PET imaging performed pre-transplant(36 months following transplantation)