An Open, Study to Assess the Safety of RGTA® (OTR4132) in Patients With Acute Ischemic Stroke (AIS)

Not Applicable

Completed

• Conditions: Stroke, Acute
• Interventions: Device: OTR4132MD

• Registration Number: NCT04083001
• Lead Sponsor: Organ, Tissue, Regeneration, Repair and Replacement

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 endovascular thrombectomy combined or not with thrombolysis.

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 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.

Study Timeline

• Study First Submitted: 2019-09-03
• Study First Submitted QC: 2019-09-05
• Study First Posted: 2019-09-10
• Study Start: 2022-03-03
• Primary Completion: 2024-06-19
• Study Completion: 2024-06-19
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-31
• Last Update Posted: 2024-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Eligible patients for this study will be included if all of the following conditions are met:

1. Age between 45 and 80 years

2. Acute ischemic stroke in anterior circulation territory, identified by magnetic resonance imaging (MRI)

3. Occlusion of anterior circulation i.e. internal carotid artery (ICA) or proximal middle cerebral artery (MCA) (M1 and/or M2 segment)

4. Volume of the infarcted lesion estimated below two thirds of the MCA territory (diffusion MRI sequence)

5. 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 *.

6. Recanalization confirmed by angiography after endovascular treatment: TICI grade 2b - 3

7. NIHSS at pre-screening (National Institute of Health Stroke Scale/Score), including hand testing: between 11 and 25

8. No significant pre-stroke disability (pre-stroke modified Rankin Score (mRS): 0-1

9. Able to follow neuro-rehabilitation programme

10. 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

Exclusion Criteria

• Eligible patients for this study will not be included if any of the following conditions are present:

  1. Previous symptomatic stroke
  2. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological evaluation
  3. Contra-indication to MRI
  4. Evidence of intracranial haemorrhage (ICH)
  5. 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
  6. History of allergy or anaphylactic reactions to any of the ingredients of OTR4132-MD or heparinoids
  7. History of Hypersensitivity or anaphylactic reactions to iodinated contrast media
  8. Severe renal failure with glomerular filtration rate (GFR) < 30 mL/min
  9. 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
  10. 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)
  11. Suspected cerebral vasculitis based on medical history and imaging
  12. Occlusions in multiple vascular territories
  13. Evidence of intracranial tumour
  14. Evidence of any prior intracranial intervention (i.e. neurosurgery, endovascular intervention)
  15. Worsening of medical or neurological conditions or per-procedures complications
  16. Any other serious, advanced, or terminal illness (investigator judgment)
  17. Pregnant or breastfeeding or women without an adequate contraceptive method
  18. Current participation in another investigation drug or device study
  19. The patient is not a member or beneficiary of the French social security system

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OTR4132MD	OTR4132MD	One medical device 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, 2 mg and 2,5 mg.

Primary Outcome Measures

Name	Time	Method
Rate of severe adverse events device related and dose limiting	7 Days	Severe adverse events

Secondary Outcome Measures

Name	Time	Method
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
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
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

Trial Locations

Locations (3)

CHU Grenoble Alpes; 🇫🇷 Grenoble, Auvergne Rhône Alpes, France

CHU Nancy; 🇫🇷 Nancy, Grand Est, France

CHU Bordeaux Pellegrin; 🇫🇷 Bordeaux, Nouvelle Aquitaine, France