Efficacy and Safety Study of GM602 in Patients With Acute Middle Cerebral Artery Ischemic Stroke Within 18 Hours - Clinical Trial for Stroke | NCT01221246

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

GM602

Placebo Comparator

About this trial

This is an interventional treatment trial for Stroke focused on measuring Acute Middle Cerebral Artery Ischemic Stroke within 18 hours

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UCLA Stroke Center (Departments of Emergency Medicine and Neurology at the University of California, Los Angeles Medical Center)
Hoag Memorial Hospital Presbyterian
Huntington Memorial Hospital Stroke Center
California Pacific Medical Center Research Institute
Sarasota Memorial Hospital
University of Louisville
Columbia University Medical Center
University Erlanger Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

GM602

Placebo Comparator

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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.

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

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.

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.

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

Full Information

NCT ID

NCT01221246

First Posted

October 11, 2010

Last Updated

August 1, 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

1. Study Identification

Unique Protocol Identification Number

NCT01221246

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

March 8, 2011 (Actual)

Primary Completion Date

July 7, 2016 (Actual)

Study Completion Date

July 7, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the 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

4. Oversight

Data Monitoring Committee

No

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stroke

Keywords

Acute Middle Cerebral Artery Ischemic Stroke within 18 hours

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GM602

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo Comparator

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

GM602

Other Intervention Name(s)

GM6, GM604, GM608, MNTF

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo Comparator

Other Intervention Name(s)

Bacteriostatic saline

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Day 90

Secondary Outcome Measure Information:

Title

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

Description

Percent change in NIHSS from baseline to 30 days in patients treated with any active dose of GM602 compared with placebo

Time Frame

Day 30

Title

Percent change in Barthel Index (BI) from baseline to 90 days in patients treated with GM602 compared to treated with placebo

Description

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.

Time Frame

Day 90

Title

Percent change in Barthel Index (BI) from baseline to 30 days in patients treated with GM602 compared to treated with placebo

Description

Percent change in BI from baseline to 30 days in patients treated with any active dose of GM602 compared with placebo

Time Frame

Day 30

Title

Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 90 days

Description

compared with placebo at each modified Rankin Scale (mRS) level at 90 days.

Time Frame

Day 90

Title

Proportion of patients treated with any active dose of GM602 compared with placebo at each mRS level at 30 days

Description

compared with placebo at each modified Rankin Scale (mRS) level at 30 days.

Time Frame

Day 30

Title

Secondary safety endpoint as measured by all cause mortality data through 3 months for patients treated with GM602 compared with placebo

Description

all cause mortality data through 3 months

Time Frame

Day 90

Other Pre-specified Outcome Measures:

Title

Primary Safety Endpoints

Description

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

Time Frame

througyh 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

No

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

Overall Study Officials: