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

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo Comparator	Placebo Comparator	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.
GM602	GM602	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.

Primary Outcome Measures

Name	Time	Method
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	Day 90	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.

Secondary Outcome Measures

Name	Time	Method
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	Day 30	Percent change in NIHSS from baseline to 30 days in patients treated with any active dose of GM602 compared with placebo
Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 90 days	Day 90	compared with placebo at each modified Rankin Scale (mRS) level at 90 days.
Percent change in Barthel Index (BI) from baseline to 30 days in patients treated with GM602 compared to treated with placebo	Day 30	Percent change in BI from baseline to 30 days in patients treated with any active dose of GM602 compared with placebo
Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 30 days	Day 30	compared with placebo at each modified Rankin Scale (mRS) level at 30 days.
Secondary safety endpoint as measured by all cause mortality data through 3 months for patients treated with GM602 compared with placebo	Day 90	all cause mortality data through 3 months
Percent change in Barthel Index (BI) from baseline to 90 days in patients treated with GM602 compared to treated with placebo	Day 90	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.

Locations (8): Huntington Memorial Hospital Stroke Center
🇺🇸
Pasadena, California, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
California Pacific Medical Center Research Institute
🇺🇸
San Francisco, California, United States
UCLA Stroke Center (Departments of Emergency Medicine and Neurology at the University of California, Los Angeles Medical Center)
🇺🇸
Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
🇺🇸
Newport Beach, California, United States
Sarasota Memorial Hospital
🇺🇸
Sarasota, Florida, United States
University Erlanger Hospital
🇺🇸
Chattanooga, Tennessee, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States