MATRISS: An Open, Study to Assess the Safety of RGTA® (OTR4132) in Patients With Acute Ischemic Stroke (AIS)
Study Details
Study Description
Brief Summary
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 combined thrombolysis and endovascular thrombectomy within 6 hours of symptoms onset.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
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 combined thrombolysis and thrombectomy.
The FIM will include up to 18 patients in up to five 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OTR4132MD one medical device (10mL) of one of the 5 available concentrations (20 μg/mL, 50 μg/mL, 100 μg/mL, 150 μg/mL, 200 μg/mL) will be administrated as a one shot-dose to the patient. The respective total dose of OTR4132 received by a patient will be one of the following: 0,20 mg, 0,50 mg, 1 mg, 1,5 mg and 2 mg. |
Device: OTR4132MD
According to Regulation (EU) 2017/745(MDR), OTR4132-MD is an implantable medical device, for short term use which is specifically intended for use in direct contact with systemic circulation system.
OTR4132-MD is by definition intended to come into contact with the patient when being injected. It is administered through intra-arterial injection, in an one-shot dose and the majority of the product is eliminated within 24 hours.
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Outcome Measures
Primary Outcome Measures
- Rate of severe adverse events device related and dose limiting [7 Days]
Severe adverse events
Secondary Outcome Measures
- Survival rates [24 hours, 7 Days, 30 Days, 90 Days]
survival rates
- All cause death [24 hours, 7 Days, 30 Days, 90 Days]
All cause death
- Stroke related death [24 hours, 7 Days, 30 Days, 90 Days]
Stroke related death
- Rate of device related adverse events (AEs) and serious adverse events (SAEs) [24 hours, 7 Days, 30 Days, 90 Days]
rate of device related adverse events
- Rate of adverse events (AEs) and serious adverse events (SAEs) procedure related [24 hours, 7 Days, 30 Days, 90 Days]
Rate of AEs and SAEs propcedure related
- Symptomatic intracranial haemorrhage [24 hours, 7 Days, 30 Days, 90 Days]
Intracranial haemorrhage
- Brain oedema on 24-hour follow-up imaging [24 hours]
brain oedema
- New ischaemic lesions [24 hours]
Ischaemic lesions in new territories on 24-hours follow-up imaging
Other Outcome Measures
- Revascularization on 24-hour follow-up imaging [24 Hours]
Revascularization on 24-hour follow-up imaging
Eligibility Criteria
Criteria
Inclusion Criteria:
- Eligible patients for this study will be included if all of the following conditions are met:
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Age 18 to 80 years
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Acute ischemic stroke in anterior circulation territory, identified by magnetic resonance imaging (MRI)
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Occlusion of anterior circulation i.e. internal carotid artery or proximal middle cerebral artery (MCA) (M1, M1/M2)
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Volume of the lesion estimated below two third of the MCA territory
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Intravenous (IV) thrombolysis performed according to European Stroke Organization (ESO) guidelines
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Intravenous Alteplase (1h infusion) terminated at least 40min before effective thrombectomy; or Intravenous Tenecteplase (bolus) terminated at least 120min before effective thrombectomy
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Endovascular thrombectomy initiated within 6 hours of stroke onset
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Angiography after endovascular treatment: TICI grade 2b - 3
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Baseline NIHSS (National Institute of Health Stroke Score), including hand testing 11 and 25 at screening
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No significant pre-stroke disability (pre-baseline modified Rankin Score (mRS) 0-1)
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Able to follow neuro-rehabilitation programme
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Patient* or legally authorized representative (family member, trusted person or physician) if patient unable to give consent has signed informed consent.
- Patients unable to give consent at baseline will go through a deferred consent procedure to continue the study (Section 12: Subject Information and Informed Consent)
Exclusion Criteria:
- Eligible patients for this study will not be included if any of the following conditions are present:
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Previous symptomatic stroke
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Pre-existing medical, neurological or psychiatric disease that would confound the neurological evaluation
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Contra-indication to MRI
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Evidence of intracranial haemorrhage (ICH)
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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
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History of allergy or anaphylactic reactions to any of the ingredients of OTR4132-MD or heparinoids
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Severe renal failure with glomerular filtration rate (GFR) < 30 mL/min
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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
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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)
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Suspected cerebral vasculitis based on medical history and imaging
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Occlusions in multiple vascular territories
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Evidence of intracranial tumour
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Evidence of any prior intracranial intervention (i.e. neurosurgery, endovascular intervention)
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Worsening of medical or neurological conditions or per-procedures complications
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Any other serious, advanced, or terminal illness (investigator judgment)
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Pregnant or breastfeeding or women without an adequate contraceptive method
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Current participation in another investigation drug or device study
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The patient is not a member or beneficiary of a social security scheme
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organ, Tissue, Regeneration, Repair and Replacement
- European Commission
- Euraxi Pharma
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2018-A03117-48