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

• ClinicalTrials.gov Identifier: NCT01221246
• Recruitment Status: Completed
• First Posted: October 14, 2010
• Last Update Posted: August 12, 2019
• Sponsor: Genervon Biopharmaceuticals, LLC
• Collaborators: University of California, Los Angeles; Huntington Hospital; Hoag Memorial Hospital Presbyterian; Columbia University; California Pacific Medical Center Research Institute; University Hospital Erlangen; Sarasota Memorial Hospital; University of Louisville
• Information provided by (Responsible Party): Genervon Biopharmaceuticals, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Stroke	Drug: GM602; Drug: Placebo Comparator	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 8, 2011
• Actual Primary Completion Date: July 7, 2016
• Actual Study Completion Date: July 7, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	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.; Other Names: GM6; GM604; GM608; MNTF
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.	Drug: 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.; Other Name: Bacteriostatic saline

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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 :

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

Other Outcome Measures:

1. Primary Safety Endpoints [ Time Frame: througyh 3 months ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

UCLA Stroke Center (Departments of Emergency Medicine and Neurology at the University of California, Los Angeles Medical Center)

Los Angeles, California, United States, 90095

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92658

Huntington Memorial Hospital Stroke Center

Pasadena, California, United States, 91105

California Pacific Medical Center Research Institute

San Francisco, California, United States, 94107

United States, Florida

Sarasota Memorial Hospital

Sarasota, Florida, United States, 34239

United States, Kentucky

University of Louisville

Louisville, Kentucky, United States, 40202

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

United States, Tennessee

University Erlanger Hospital

Chattanooga, Tennessee, United States, 37403

Sponsors and Collaborators

Genervon Biopharmaceuticals, LLC

University of California, Los Angeles

Huntington Hospital

Hoag Memorial Hospital Presbyterian

Columbia University

California Pacific Medical Center Research Institute

University Hospital Erlangen

Sarasota Memorial Hospital

University of Louisville

Investigators

• Principal Investigator: Arbi G Ohanian, MD; Huntington Memorial Hospital
• Principal Investigator: Sidney Starkman, MD; UCLA Stroke Center
• Principal Investigator: Jeff Saver, MD; UCLA Stroke Center
• Principal Investigator: David Brown, MD; Hoag Memorial Hospital Presbyterian
• Principal Investigator: Stephan A Mayer, M.D.; Columbia University
• Principal Investigator: Nobl Barazangi, M.D.; California Pacific Medical Center Research Institute
• Principal Investigator: Thomas G Devlin, M.D.; University Erlanger Hospital
• Principal Investigator: Mauricio Concha, M.D.; Sarasota Memorial Hospital
• Principal Investigator: Anand Vaishnav, M.D.; University of Louisville

More Information

• Responsible Party: Genervon Biopharmaceuticals, LLC
• ClinicalTrials.gov Identifier: NCT01221246
• Other Study ID Numbers: GEN-002
• First Posted: October 14, 2010
• Last Update Posted: August 12, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Genervon Biopharmaceuticals, LLC:

Acute Middle Cerebral Artery Ischemic Stroke within 18 hours

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases