Efficacy and Safety Study of GM602 in Patients With Acute Middle Cerebral Artery Ischemic Stroke Within 18 Hours

Study Overview
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Brief Summary
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The purpose of this research study is to determine whether the investigational drug GM602, is effective and safe in the treatment of ischemic stroke (strokes caused by a blood clot blocking the flow of blood through one, or more of the blood vessels supplying the brain) when administered up to 18 hours after symptoms begin.

Detailed Description
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Stroke is a serious and life threatening disease. About 85% of all strokes are ischemic, caused by a blood clot or plaque that blocks a blood vessel in the brain. The thrombolytic drug tissue plasminogen activator (tPA) is the only early treatment for acute ischemic stroke approved by the FDA. Treatment with tPA must be administered within three hours of the stroke onset. Furthermore, tPA treatment carries a recognized risk of bleeding in the brain. GM602 is an investigational drug that may act as a neuroprotectant in patients who have had a stroke. It is thought to stop cell death and reduce inflammation in the injured area of the brain. This study is designed to evaluate the safety and efficacy of GM602 administered intravenously to patients in three consecutive daily doses of 320 mg/dose or 480 mg/dose, the initial dose administered within 18 hours after onset of acute ischemic stroke in the Middle Cerebral artery region.

Official Title
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A Phase 2 Double Blinded, Randomized, Placebo Controlled Dose Escalation Study to Evaluate the Efficacy and the Safety of GM602 in Patients With Acute Middle Cerebral Artery Ischemic Stroke Within an 18-hour Treatment Window

Conditions
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Stroke

Intervention / Treatment
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* Drug: GM602
* Drug: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years old Be eligible for MRI or CT scan Have suffered acute ischemic stroke in the middle cerebral artery (MCA) distribution, as verified by the Screening diffusion-weighted imaging (DWI) abnormality and Screening perfusion-weighted imaging pressure-work index (PWI ) abnormality Have NIH Stroke Scale (NIHSS) score total score of 9-20 inclusive at screening Have suffered acute ischemic stroke within 18 hours Have been functionally independent with a Modified Rankin Score (mRS) of 0 or 1 prior to suffering stroke Patients who received tPA or FDA approved mechanical device can also enroll completed informed consent form Exclusion Criteria: Have history of stroke in the past 3 months Cannot be evaluated using MRI/CT Have stroke of the brainstem or cerebellum Have clinical presentation consistent with acute MI by EKG criteria (STEMI) at screening Have hemorrhage revealed by CT or MRI scan Have > 1/3 MCA territory HYPER intensity as seen on MRI OR >1/3 MCA territory HYPO intensity as seen on CT Have blood sugar level >400 mg/DL or<50 mg/dL Have kidney disease, creatinine > 2.0 Have had recent (within 90 days) serious head trauma or head trauma with loss of consciousness Have any prior history of seizure Have clinically relevant pre-existing neurological deficit (Historical Rankin score ≥ 2) Have any other known clinically significant medical disorder (cardiovascular, hepatic, renal, endocrine, respiratory, immunological, cancer, AIDS) Life expectancy of less than 6 months due to comorbid conditions Women of child bearing potential who are pregnant or breast-feeding or unable to practice birth control during the study period Have participated in any other trial of an investigational agent within 90 days prior to screening Informed consent cannot be obtained Unable to participate in study visits

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: GM602<br>First 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 320 mg/dose of GM602 or placebo in a 2:1 ratio, then the next 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 480 mg/dose of GM602 or placebo in a 2:1 ratio. Concurrently, 18 severe patients will be randomized in the same manner. Total 12 moderate and 12 severe patients will receive GM602. | Drug: GM602<br>* First 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 320 mg/dose of GM602 or placebo in a 2:1 ratio, then the next 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 480 mg/dose of GM602 or placebo in a 2:1 ratio. Concurrently, 18 severe patients will be randomized in the same manner. Total 12 moderate and 12 severe patients will receive GM602.<br>* Other names: MNTF;|
| Placebo Comparator: Placebo Comparator<br>First 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 320 mg/dose of GM602 or placebo in a 2:1 ratio; then the next 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 480 mg/dose of GM602 or placebo in a 2:1 ratio. Concurrently, 18 severe patients will be randomized in the same manner. Total 6 moderate and 6 severe patients receive Placebo. | Drug: Placebo Comparator<br>* First 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 320 mg/dose of GM602 or Matching Placebo (Bacteriostatic Saline) for GM602 in a 2:1 ratio, then the next 9 moderate patients (either co-treated or not co-treated) will be randomized to receive 480 mg/dose of GM602 or placebo in a 2:1 ratio. Concurrently, 18 severe patients will be randomized in the same manner. Total 6 moderate and 6 severe patients will receive placebo.<br>* Other names: Bacteriostatic saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Outcome as measured by the difference in percent change in NIHSS from baseline to 90 days in patients treated with GM602 within 18 hours compared to treated with placebo as primary efficacy endpoint | NIH Stroke Scale is a standardized neurological examination intended to describe the neurological deficits found in large groups of stroke patients participating in treatment trials. Percent change from baseline in NIHSS is calculated and compared. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in Barthel Index (BI) from baseline to 90 days in patients treated with GM602 compared to treated with placebo | The Barthel Index is measured using both historical and direct observational information. It measures self-care and mobility and will help define the degree of residual disability. Percent change from baseline in BI is calculated. | Day 90 | 
| Percent change in Barthel Index (BI) from baseline to 30 days in patients treated with GM602 compared to treated with placebo | Percent change in BI from baseline to 30 days in patients treated with any active dose of GM602 compared with placebo | Day 30 | 
| Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 90 days | compared with placebo at each modified Rankin Scale (mRS) level at 90 days. | Day 90 | 
| Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 30 days | compared with placebo at each modified Rankin Scale (mRS) level at 30 days. | Day 30 | 
| Secondary safety endpoint as measured by all cause mortality data through 3 months for patients treated with GM602 compared with placebo | all cause mortality data through 3 months | Day 90 | 
| Functional Outcome as measured by the difference in percent change in NIHSS from baseline to 30 days in patients treated with GM602 compared to treated with placebo | Percent change in NIHSS from baseline to 30 days in patients treated with any active dose of GM602 compared with placebo | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Middle Cerebral Artery Ischemic Stroke within 18 hours