Efficacy and safety of Neu2000, a multi-target drug designed to prevent both NMDA receptor-mediated excitotoxicity and free radical toxicity, will be investigated in acute ischemic stroke patients receiving endovascular treatment to remove clot within 12 hours following stroke onset. Neu2000KWL will be administered before endovascular treatment.
Neu2000 was designed as a multi-target neuroprotectant preventing both the NMDA receptor, a Ca2+ -permeable glutamate receptor, and free radicals, two major routes of brain cell death in stroke. Neu2000 is a moderate NR2B-selective NMDA receptor antagonist and spin trapping molecule (=free radical scavenger or antioxidant). Therapeutic potential of Neu2000 has been well demonstrated in four animal models of stroke with better efficacy and therapeutic time windows than either NMDA receptor antagonist or anti-oxidant advanced to clinical trials. In human phase I studies of 165 healthy subjects conducted in the United States and China, Neu2000KWL showed promising safety profiles without any serious adverse events up to a single intravenous infusion of 6000 mg that is far beyond the therapeutic target dose determined in animal models of transient ischemic stroke. Very recently, acute endovascular recanalization therapy has been introduced as the new standard care of care in acute ischemic stroke. The present study is aimed to examine efficacy and safety of Neu2000KWL in acute ischemic stroke patients receiving endovascular thrombectomy within 12 hours of stroke onset. This is a randomized trial, with placebo comparison, of comparing functional outcome at week 12 after 10 times of administration for five days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
496
1st infusion of 750mg in patients receiving endovascular therapy within 12 hours following ischemic stroke onset followed by 9 consecutive infusions of 500 mg at intervals of 12 ± 1 hours, twice a day.
1st infusion of the same volume of saline in patients receiving endovascular therapy within 12 hours following ischemic stroke onset followed by 9 consecutive infusions of same volume of saline at intervals of 12 ± 1 hours, twice a day
Inje University Busan Paik Hospital
Busan, South Korea
mRS score evaluated at 12 week after the first dose of drug (Nelonemdaz or Placebo).
Time frame: week12
Proportion of mRS 0-2 evaluated at week 5 and week 12 after the first dose of drug (Nelonemdaz or Placebo).
Time frame: week5, week12
mRS score evaluated at week 5 after the first dose of investigational drug (Nelonemdaz or Placebo).
Time frame: week5
Proportion of mRS 0 measured at week 5 and week 12 after the first dose of investigational drug (Nelonemdaz or Placebo).
Time frame: week5, week12
Proportion of NIHSS 0-4 evaluated within 24 hours (Within 72 hours if weekend is included), 5 week, 12 week after the last injection of drug. (Evaluating 43 points for deaths)
Time frame: 24hour(or 72hour), week5, week12
Volume of Ischemic stroke based on brain MRI diffusion weighted imaging within 24 hours and at week 12. (If MRI is not available, reading will be performed based on CT scan.)
Time frame: 24hour, week12
Proportion of Barthel Index≥95 evaluated at week 5 and week 12
Time frame: week5, week12
Occurrence rate of Symptomatic intracranial hemorrhage (SICH) described and defined by this study occurring within 24 hours after the last injection
\[Definition of Symptomatic intracranial hemorrhage (SICH)\] In the case that brain imaging confirms intracranial hemorrhage with neurological deterioration. (NIHSS score≥4 points) neurological deterioration. (NIHSS score≥4 points)
Time frame: 24hour
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