This clinical study is designed to evaluate the efficacy and safety of the combination therapy of SP-8203 (otaplimastat) and thrombolytic standard of care in acute ischemic stroke patient. As a standard of care, thrombolytic therapy (for instance, recombinant tissue plasminogen activator) will be administered. When reperfusion is not achieved in spite of thrombolytic therapy, endovascular therapy can be performed.
Intravenous administration of SP-8203 (otaplimastat), a multipotent neuroprotectant inhibiting matrix metalloprotease activity, significantly reduced infarct volume and recombinant tissue plasminogen activator (rtPA)/ ischemic-induced damage in animal models. This clinical study is designed to evaluate the efficacy and safety of the combination therapy of SP-8203 (otaplimastat) and thrombolytic standard of care in acute ischemic stroke patient. As a standard of care, thrombolytic therapy (for instance, recombinant tissue plasminogen activator) will be administered. When reperfusion is not achieved in spite of thrombolytic therapy, endovascular therapy can be performed. A total of 852 participants will be enrolled in double-blind, randomized and parallel design with 426 participants assigned to 80 mg/day SP-8203 arm or placebo arm, respectively. Eligible participants are the patients with neurologic deficit of ≥8 point on National Institute of Health Stroke Scale (NIHSS) score. The participant will receive the study intervention a total of 6 times, with 12 hours intervals. Imaging test will be performed using validated machine and method. The participant will have initial brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) performed within 6 hours before or after the administration of study intervention, and brain Computed Tomography (CT) will be performed at 24±3 hours after completion of the first administration of study intervention. Brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) will be followed-up on Day 5, and additionally the participant will undergo additional functional and neurological evaluations for up to 90 days. When unexpected serious adverse reaction occurs during the clinical study, Data Safety Monitoring Board (DSMB) will be convened to validation safety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
852
Dong-A University Hospital
Busan, South Korea
RECRUITINGUlsan University Hospital
Ulsan, South Korea
RECRUITINGProportion of participants with modified Rankin Scale (mRS) 0-1
Proportion of participants with modified Rankin Scale (mRS) 0-1 at Day 90 in patients with acute ischemic stroke requiring thrombolytic standard of care
Time frame: Day 90
Incidence of parenchymal hematoma observed on brain Computed Tomography (CT) scan
Incidence of parenchymal hematoma observed on brain Computed Tomography (CT) scan performed at 24±3 hours in accordance with European Cooperative Acute Stroke Study (ECASS) I and II criteria, after the administration of SP-8203 in conjunction with thrombolytic standard of care
Time frame: Day 1
Proportion of participants with modified Rankin Scale (mRS) 0-1
Proportion of participants with modified Rankin Scale (mRS) 0-1 at Day 30 in patients with acute ischemic stroke requiring thrombolytic standard of care
Time frame: Day 30
Proportion of participants with modified Rankin Scale (mRS) 0-2
Proportion of participants with modified Rankin Scale (mRS) 0-2 at Day 30 and Day 90 in the patients with acute ischemic stroke requiring thrombolytic standard of care
Time frame: Day 30 and Day 90
Change from Baseline in National Institute of Health Stroke Scale (NIHSS) scores
The change in the National Institute of Health Stroke Scale (NIHSS) scores until 90 day in subjects with acute ischemic stroke requiring rtPA standard of care. The maximum total score is 42 points, which indicates the most critical condition and the minimum total score is 0, which indicates no neurologic deficit.
Time frame: Day 0 (baseline), Day 3, Day 5, Day 30 and Day 90
Fold change in infarct growth classified by modified treatment in cerebral ischemia (mTICI) grade within 5 days
MRI (DWI) imaging outcomes
Time frame: Day 5
The incidence of serious adverse events
The incidence of serious adverse events
Time frame: follow-up to 90 days after the first study intervention administration
The rate of death
The rate of death due to any cause
Time frame: follow-up to 90 days after the first study intervention administration
The incidence rate of adverse events, and adverse drug reaction
The incidence rate of adverse events, and adverse drug reaction
Time frame: follow-up to 90 days after the first study intervention administration
The incidence of symptomatic Intracranial Hemorrhage (sICH)
The incidence of symptomatic Intracranial Hemorrhage (sICH) occurring within 5 days of administration according to the definition described on the protocol
Time frame: within 5 days from the first study intervention administration
The Incidence of major systemic bleeding
The Incidence of major systemic bleeding according to the International Society of Thrombosis and Hemostasis (ISTH) definition
Time frame: within 5 days after the first study intervention administration
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