Clinical trial NCT04083001: An Open, Study to Assess the Safety of RGTA® (OTR4132) in Patients With Acute Ischemic Stroke (AIS)
Official title: An Open, Multi-centre Study to Assess the Safety and Tolerability of RGTA® (OTR4132) in Patients With Acute Ischemic Stroke (AIS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke, Acute
Keywords: Stroke
FIM
OTR3
Lead sponsor: Organ, Tissue, Regeneration, Repair and Replacement
Sponsor class: INDUSTRY
Collaborators: name: European Commission
name: Euraxi Pharma
First posted: 2019-09-10
Enrollment: 19
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of severe adverse events device related and dose limiting
timeFrame: 7 Days
Secondary outcomes:
measure: Survival rates
timeFrame: 24 hours, 7 Days, 30 Days, 90 Days
measure: All cause death
timeFrame: 24 hours, 7 Days, 30 Days, 90 Days
measure: Stroke related death
timeFrame: 24 hours, 7 Days, 30 Days, 90 Days
measure: Rate of device related adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 24 hours, 7 Days, 30 Days, 90 Days
measure: Rate of adverse events (AEs) and serious adverse events (SAEs) procedure related
timeFrame: 24 hours, 7 Days, 30 Days, 90 Days
measure: Symptomatic intracranial haemorrhage
timeFrame: 24 hours, 7 Days, 30 Days, 90 Days
measure: Brain oedema on 24-hour follow-up imaging
timeFrame: 24 hours
measure: New ischaemic lesions
timeFrame: 24 hours
Other outcomes:
measure: Revascularization on 24-hour follow-up imaging
timeFrame: 24 Hours
Locations:
city: Grenoble
country: France
facility: CHU Grenoble Alpes
state: Auvergne Rhône Alpes
city: Nancy
country: France
facility: CHU Nancy
state: Grand Est
city: Bordeaux
country: France
facility: CHU Bordeaux Pellegrin
state: Nouvelle Aquitaine
Study officials:
affiliation: CHU Grenoble Alpes
name: Olivier Detante
role: PRINCIPAL_INVESTIGATOR
References: