Clinical trial NCT01221246: Efficacy and Safety Study of GM602 in Patients With Acute Middle Cerebral Artery Ischemic Stroke Within 18 Hours
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
Keywords: Acute Middle Cerebral Artery Ischemic Stroke within 18 hours
Lead sponsor: Genervon Biopharmaceuticals, LLC
Sponsor class: INDUSTRY
Collaborators: name: University of California, Los Angeles
name: Huntington Hospital
name: Hoag Memorial Hospital Presbyterian
name: Columbia University
name: California Pacific Medical Center Research Institute
name: University Hospital Erlangen
name: Sarasota Memorial Hospital
name: University of Louisville
First posted: 2010-10-14
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 90
Secondary outcomes:
measure: 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
timeFrame: Day 30
measure: Percent change in Barthel Index (BI) from baseline to 90 days in patients treated with GM602 compared to treated with placebo
timeFrame: Day 90
measure: Percent change in Barthel Index (BI) from baseline to 30 days in patients treated with GM602 compared to treated with placebo
timeFrame: Day 30
measure: Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 90 days
timeFrame: Day 90
measure: Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 30 days
timeFrame: Day 30
measure: Secondary safety endpoint as measured by all cause mortality data through 3 months for patients treated with GM602 compared with placebo
timeFrame: Day 90
Other outcomes:
measure: Primary Safety Endpoints
timeFrame: througyh 3 months
Locations:
city: Los Angeles
country: United States
facility: UCLA Stroke Center (Departments of Emergency Medicine and Neurology at the University of California, Los Angeles Medical Center)
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Pasadena
country: United States
facility: Huntington Memorial Hospital Stroke Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute
state: California
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chattanooga
country: United States
facility: University Erlanger Hospital
state: Tennessee
Study officials:
affiliation: Huntington Memorial Hospital
name: Arbi G Ohanian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCLA Stroke Center
name: Sidney Starkman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCLA Stroke Center
name: Jeff Saver, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hoag Memorial Hospital Presbyterian
name: David Brown, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Stephan A Mayer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: California Pacific Medical Center Research Institute
name: Nobl Barazangi, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Erlanger Hospital
name: Thomas G Devlin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sarasota Memorial Hospital
name: Mauricio Concha, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Louisville
name: Anand Vaishnav, M.D.
role: PRINCIPAL_INVESTIGATOR
References: