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

Stroke Clinical Trial

— GMAIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01221246
• Other study ID #: GEN-002
• Status: Completed
• Phase: Phase 2
• Start date: March 8, 2011
• Est. completion date: July 7, 2016

Study information

• Verified date: July 2019
• Source: Genervon Biopharmaceuticals, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: July 7, 2016
• Est. primary completion date: July 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

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

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• 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.
• Placebo Comparator
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.

Locations

Country	Name	City	State
United States	University Erlanger Hospital	Chattanooga	Tennessee
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	University of Louisville	Louisville	Kentucky
United States	Columbia University Medical Center	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Huntington Memorial Hospital Stroke Center	Pasadena	California
United States	California Pacific Medical Center Research Institute	San Francisco	California
United States	Sarasota Memorial Hospital	Sarasota	Florida

Sponsors (9)

Lead Sponsor	Collaborator
Genervon Biopharmaceuticals, LLC	California Pacific Medical Center Research Institute, Columbia University, Hoag Memorial Hospital Presbyterian, Huntington Hospital, Sarasota Memorial Hospital, University Hospital Erlangen, University of California, Los Angeles, University of Louisville

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Primary Safety Endpoints	Adverse events, Fatal intracranial hemorrhage (ICH). nonfatal symptomatic parenchymal hemorrhage, or other symptomatic ICH, Neurological deterioration during hospitalization, Number of seizures after stroke, Respiratory compromise as observed by respiratory rate	througyh 3 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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	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