Field Randomization of Nerinetide (NA-1) Therapy in Early Responders

Study Overview
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Brief Summary
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The purpose of this study is to determine whether nerinetide (NA-1) is effective in reducing global disability in patients with acute cerebral ischemia if administered early after symptom onset.

Detailed Description
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Nerinetide (NA-1) is being developed as an emergency drug aimed at reducing global disability in patients with acute cerebral ischemia if administered early after symptom onset. The primary objective is to determine the efficacy of nerinetide in reducing global disability in patients with acute stroke. The secondary objectives are to determine the efficacy of nerinetide in reducing functional dependence, reducing mortality rate, reducing worsening of stroke, improving neurological outcome and improving activities of daily living. The leading safety objectives are to determine the effect of administering a target dose of 2.60 mg/kg (up to a maximum dose of 270 mg) IV infusion of nerinetide within three hours of symptom onset by paramedics in the field on serious adverse events and 90-day mortality. This trial is a multicenter, randomized, double-blind, placebo-controlled, single dose study initiated prehospital in the ambulance. It is being conducted using Emergency Medical Services (EMS) in Canada. Subjects with suspected acute stroke will be identified in the field by trained paramedics using the approved stroke protocol in use by the local EMS system, and further screened for eligibility and approval by an on-call trial physician. The paramedics will administer the study drug. Upon arrival at the emergency department, subjects will receive standard-of-care. An Independent Data Monitoring Committee will perform safety reviews of the clinical data.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Intravenous NA-1 Initiated by Paramedics in the Field for Acute Cerebral Ischemia Within Three Hours of Symptom Onset

Conditions
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Acute Cerebral Ischemia

Intervention / Treatment
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* Drug: Nerinetide (NA-1)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provisional diagnosis of acute stroke as identified by paramedics using the local stroke triage tool Respiratory rate 12-24 breaths per minute Oxygen saturation ≥ 90% on room air Systolic blood pressure < 90 or > 220 mmHg Weight 45-120 kg Last seen in usual state of health less than 3 hours before anticipated study drug initiation Independently ambulatory with or without devices prior to event LAMS score of 2-5 for at least 15 minutes and remains 2-5 at time of randomization Exclusion Criteria: Lack of IV access Canadian Triage and Acuity Scale Level 1 and/or uncorrected airway, breathing or significant circulatory problem Blood sugar < 3 mmol/L (< 55 mg/dL) Seizure at onset of symptoms or observed by paramedic Glasgow coma score of <10 Major head trauma in the last three months Recent stroke in the last three months Known or presumptive signs of pregnancy or breastfeeding Prisoner Long term care facility resident Known advance directive to not resuscitate Known participation in a clinical trial with an investigational drug or device within 30 days preceding this trial Pre-existing neurologic, psychiatric, or advanced systemic condition that would preclude obtaining the neurological or functional outcome evaluations

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nerinetide (NA-1)<br>2.60 mg/kg of nerinetide (up to a maximum dose of 270 mg) administered as a single 10 minute IV infusion using an ambulatory infusion pump early after stroke symptom onset. | Drug: Nerinetide (NA-1)<br> <br> |
| Placebo Comparator: Placebo<br>Placebo administered as a single 10 minute IV infusion using an ambulatory infusion pump early after stroke symptom onset. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS) scale | The percentage of responders, using a sliding dichotomy on the mRS | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mRS shift analysis | Shift to reduced functional dependence analyzed across the whole distribution of scores on the mRS | 90 Days or the last rating | 
| Mortality rate | A reduction in mortality as defined by event rate (proportion, expressed as a percentage) | 90 Days | 
| Worsening of stroke rate | A reduction in proportion of participants with worsening of stroke. Worsening of stroke is defined as progression, or hemorrhagic transformation, of the index stroke as documented in the study CRF that (i) is deemed life-threatening and/or (ii) results in increased disability as gauged by a ≥4 point increase from lowest NIHSS during hospitalization and/or (iii) results in death. | 90 Days | 
| National Institutes of Health Stroke Scale (NIHSS) | Proportion of subjects with good neurological outcome, as defined by a score of 0-1 on the NIHSS | 90 Days or the last rating | 
| Barthel Index | Proportion of subjects with functional independence in activities of daily living, as defined by a score of ≥ 95 on the Barthel Index | 90 Days or the last rating | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Ischemia, Prehospital, NA-1, Modified Rankin Scale, Haemorrhagic stroke, Transient ischemic attack, Nerinetide