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

Study Overview
=================
Brief Summary
-----------------
A Phase II, randomized, blinded, placebo-controlled, parallel group study with patients experiencing a large vessel occlusion acute ischemic stroke who are selected for endovascular revascularization. Participants will be given a 48 h infusion of either 0.5 mL/kg/h RNS60 (up to a maximum of 60 mL/h), 1 mL/kg/h RNS60 (up to a maximum of 120 mL/h), or 1 mL/kg/h (up to a maximum of 120 mL/h) placebo (normal saline) starting within 30 minutes of consent after confirmation of candidacy for endovascular thrombectomy.

Detailed Description
-----------------
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 60 mL/h), 1 mL/kg/h RNS60 (up to a maximum of 120 mL/h), or 1 mL/kg/h (up to a maximum of 120 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.

Official Title
-----------------
RESCUE: A Randomized, Blinded, Placebo-controlled, Parallel Group Design to Determine the Safety of RNS60 in Large Vessel Occlusion Stroke Patients Undergoing Endovascular Thrombectomy

Conditions
-----------------
Stroke, Ischemic

Intervention / Treatment
-----------------
* Drug: RNS60
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 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 ASPECTS 0-4. Evidence of absence of collateral circulation on qualifying imaging (Collateral score of 0 or 1). 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 within 6 months prior to Screening including non-Q wave MI; Diagnosis of 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 MRI imaging (Non- 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 > 450 ms at Screening. Any other symptom that in the investigator's opinion may complicate or preclude the subject from participating in this trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RNS60 0.5 mL/kg/h<br>RNS60 0.5 mL/kg/h infusion for 48h (up to a maximum of 60 mL/kg) starting within 30 min of randomization (but prior to arterial access closure) | Drug: RNS60<br>* RNS60 injection solution<br>|
| Experimental: RNS60 1 mL/kg/h<br>RNS60 1 mL/kg/h infusion for 48h (up to a maximum of 120 mL/kg) starting within 30 min of randomization (but prior to arterial access closure) | Drug: RNS60<br>* RNS60 injection solution<br>|
| Placebo Comparator: Placebo 1 mL/kg/h<br>Placebo (normal saline) 1 mL/kg/h infusion for 48h (up to a maximum of 120 mL/kg) starting within 30 min of randomization (but prior to arterial access closure) | Drug: Placebo<br>* Placebo injection solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with serious adverse events |  | 90 days | 
| Mortality: proportion of participants alive |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean mRS score | mRS = Modified Rankin Scale | 90 days | 
| Reduction in mortality rate | Lower event rate on the Kaplan Meier survival curve | 90 days | 
| Mean NIHSS score | NIHSS = National Institutes of Health Stroke Scale | 90 days | 
| Proportion of participants with a worsening of stroke | Worsening of stroke defined as progression, or hemorrhagic transformation, of the index stroke as documented by medical imaging and that is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥4 point increase from lowest NIHSS during hospitalization and/or (c) results in death | 90 days | 
| Mean BI | Mean Barthel Index (BI) at Day 90 relative to pre-stroke BI | 90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endovascular Thrombectomy