An Open, Multi-centre Study to Assess the Safety and Tolerability of RGTA® (OTR4132) in Patients With Acute Ischemic Stroke (AIS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 6
- 主要终点
- Rate of severe adverse events device related and dose limiting
研究概览
简要总结
RGTA® (ReGeneraTing Agent) are synthetic polysaccharides mimicking extra-cellular matrix scaffold elements and protective agents called Heparan Sulphates (HSPGs).
OTR4132-MD is provided as a sterile injectable medical device. OTR4132-MD is indicated in anterior circulation acute ischemic stroke (AIS) patients re-vascularized (TICI score 2b - 3) by endovascular thrombectomy combined or not with thrombolysis.
详细描述
The promising results of OTR4132-MD in the treatment of acute ischemic stroke in animal studies and the excellent results of biocompatibility tests reported in the Investigator's Brochure allowed to design a clinical investigation in humans named MATRISS. As this is a First-In-Man (FIM) study assessing OTR4132-MD, it is designed as a single ascending dose (SAD) to evaluate the safety, tolerability of a single intra-arterial injection of OTR4132-MD in AIS patients treated with thrombectomy combined or not with thrombolysis.
The FIM will include up to 19 patients in up to six dose groups. Each group will comprise 3 subjects. This FIM study will also monitor a dose response relationship in humans: lesion volume change throughout the study period. Patients will be given a single intra-arterial injection of OTR4132-MD with a predefined dose of OTR4132. In the first dose group, the OTR4132 dose is 0.20 mg.
The results of this study will serve as a groundwork for the design of a pivotal study in the intended patient population.
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
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible patients for this study will be included if all of the following conditions are met:
- •Age between 45 and 80 years
- •Acute ischemic stroke in anterior circulation territory, identified by magnetic resonance imaging (MRI)
- •Occlusion of anterior circulation i.e. internal carotid artery (ICA) or proximal middle cerebral artery (MCA) (M1 and/or M2 segment)
- •Volume of the infarcted lesion estimated below two thirds of the MCA territory (diffusion MRI sequence)
- •Endovascular thrombectomy initiated within 6 hours of stroke onset with known stroke onset time or Endovascular thrombectomy initiated within 6 to 16 hours of symptoms onset (last know well in case of unwitnessed onset) with a mismatch on brain MRI defined in *.
- •Recanalization confirmed by angiography after endovascular treatment: TICI grade 2b - 3
- •NIHSS at pre-screening (National Institute of Health Stroke Scale/Score), including hand testing: between 11 and 25
- •No significant pre-stroke disability (pre-stroke modified Rankin Score (mRS): 0-1
- •Able to follow neuro-rehabilitation programme
- •Patient** or legally authorized representative (family member or trusted person if patient unable to give consent) or independent physician (if patient unable to give consent and if an authorized representative cannot be reached) has signed informed consent).
- •Perfusion core/penumbra mismatch:
- •Infarct core volume <70 mL
- •and critically hypoperfused volume/infarct core volume >1.8
- •and mismatch volume >15mL ** Patients unable to give consent at baseline will go through a deferred consent procedure to continue the study
排除标准
- •Eligible patients for this study will not be included if any of the following conditions are present:
- •Previous symptomatic stroke
- •Pre-existing medical, neurological, or psychiatric disease that would confound the neurological evaluation
- •Contra-indication to MRI
- •Evidence of intracranial haemorrhage (ICH)
- •At the discretion of the investigator, patients with co-morbidities associated with a life expectancy of less than 3 months or co-morbidities that could influence the study results or would complicate assessment of outcomes (e.g. dementia, psychiatric disease) or would make clinical follow-up difficult
- •History of allergy or anaphylactic reactions to any of the ingredients of OTR4132-MD or heparinoids
- •History of Hypersensitivity or anaphylactic reactions to iodinated contrast media
- •Severe renal failure with glomerular filtration rate (GFR) < 30 mL/min
- •Severe uncontrolled arterial hypertension e.g. systolic blood pressure > 185 mmHg or diastolic blood pressure > 110 mmHg, or intravenous medication necessary to reduce blood pressure
- •Increased risk of haemorrhage (such as medical history of significant bleeding disorders, major surgery or significant trauma in the past 3 months, any history of central nervous damage or suspected intracranial haemorrhage, symptoms suggestive of subarachnoid haemorrhage, even if the MRI is normal, international normalized ratio (INR)>1.3 or activated partial thromboplastin time (aPTT)>ULN (upper limit of normal)
- •Suspected cerebral vasculitis based on medical history and imaging
- •Occlusions in multiple vascular territories
- •Evidence of intracranial tumour
- •Evidence of any prior intracranial intervention (i.e. neurosurgery, endovascular intervention)
- •Worsening of medical or neurological conditions or per-procedures complications
- •Any other serious, advanced, or terminal illness (investigator judgment)
- •Pregnant or breastfeeding or women without an adequate contraceptive method
- •Current participation in another investigation drug or device study
- •The patient is not a member or beneficiary of the French social security system
结局指标
主要结局
Rate of severe adverse events device related and dose limiting
时间窗: 7 Days
Severe adverse events
次要结局
- Rate of adverse events (AEs) and serious adverse events (SAEs) procedure related(24 hours, 7 Days, 30 Days, 90 Days)
- Symptomatic intracranial haemorrhage(24 hours, 7 Days, 30 Days, 90 Days)
- Brain oedema on 24-hour follow-up imaging(24 hours)
- New ischaemic lesions(24 hours)
- Stroke related death(24 hours, 7 Days, 30 Days, 90 Days)
- Rate of device related adverse events (AEs) and serious adverse events (SAEs)(24 hours, 7 Days, 30 Days, 90 Days)
- Survival rates(24 hours, 7 Days, 30 Days, 90 Days)
- All cause death(24 hours, 7 Days, 30 Days, 90 Days)