Safety of RNS60 in Large Vessel Occlusion Stroke Patients Undergoing Endovascular Thrombectomy

This study is a Phase II, randomized, blinded, placebo-controlled, parallel group design. Participants experiencing a large vessel occlusion acute ischemic stroke who are selected for endovascular revascularization will be given a 48 h infusion of either 0.5 mL/kg/h RNS60 (up to a maximum of 65 mL/h), 1.0 mL/kg/h RNS60 (up to a maximum of 130 mL/h), or 1.0 mL/kg/h (up to a maximum of 130 mL/h) placebo (normal saline) starting within 30 minutes of consent after confirmation of candidacy for endovascular thrombectomy and prior to arterial closure. Outcomes of the main trial will be evaluated throughout a 90 day observation period.

Inclusion criteria

• Acute ischemic stroke (AIS) selected for emergency endovascular treatment.
• Age 18 years or older.
• Onset (last-known-well) time to randomization time within 24 hours.
• Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS)

• NIHSS > 5 for internal carotid artery (ICA) and M1-middle cerebral artery (MCA) occlusion or
• NIHSS > 10 for M2-MCA occlusion.
• Confirmed symptomatic intracranial occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA. Tandem extracranial carotid and intracranial occlusions are permitted.
• Pre-stroke (24 hours prior to stroke onset) historical modified Rankin Scale (mRS) ≤2. Patient must be living independently without requiring nursing care.
• Qualifying imaging performed less than 2 hours prior to randomization.
• Consent process completed as per applicable laws and regulation and the IRB requirements.

Exclusion criteria

• Evidence of a large core of established infarction defined as Alberta Stroke Program Early Computerized Tomography Score (ASPECTS) 0-4.
• Evidence of absence of collateral circulation on qualifying imaging (collateral score of 0 or 1 if multiphase computed tomography angiography (mCTA) is used, or absence of adequate ischemic penumbra in the judgment of the Investigator if computed tomographic perfusion (CTP) is used).
• Any evidence of intracranial hemorrhage or mass lesion on the qualifying imaging.
• Planned use of an endovascular device not having approval or clearance by the relevant regulatory authority.
• Endovascular thrombectomy procedure is completed as defined by the presence of arterial access closure.
• Clinical history, past imaging or clinical judgment suggesting that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention.
• Estimated or known weight > 130 kg (287 lbs).
• Known pregnant/lactating female.
• Myocardial infarction (MI) within 6 months prior to Screening including non-Q wave MI; Diagnosis of congestive heart failure (CHF) with either:

• current clinical signs and symptoms of ventricular dysfunction (e.g., edema, shortness of breath),
• CHF medication adjustment within the prior 30 days or
• ejection fraction (if report available) of 30% or less measured in the 6 months prior to Screening; as either medically documented or reported by patient or another person considered by the Investigator to be reasonably reliable.
• Known renal impairment defined as requiring renal replacement therapy (hemo- or peritoneal dialysis).
• Inability to have magnetic resonance imaging (MRI) (Non-magnetic resonance [MR] compatible implants or any other foreseeable reason, including claustrophobia)
• Severe or fatal comorbid illness that will prevent improvement or follow up.
• Inability to complete follow-up treatment to Day 90.
• Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding trial inclusion and throughout the duration of the trial.
• Reported known seizure at time of stroke onset.
• Ischemic stroke within previous 30 days.
• Patients in normal sinus rhythm with a known QTcF > 460 ms at Screening.
• Any other symptom that in the investigator's opinion may complicate or preclude the subject from participating in this trial.