Clinical trial NCT05041010: Rescues On Reperfusion Damage In Cerebral Infarction by Nelonemdaz
Official title: A Phase III, Double-blind, Randomized, Placebo-controlled, Multi-center Study to Assess the Efficacy and Safety of Nelonemdaz in Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: Neu2000KWL
Neuroprotection
endovascular therapy
glutamate
free radical
Lead sponsor: GNT Pharma
Sponsor class: INDUSTRY
First posted: 2021-09-10
Enrollment: 496
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

The trial subjects should satisfy all the following criteria.

1. Adults≥19 years
2. Patients who can start endovascular therapy within 12 hours after the symptomatic onset of Ischemic stroke.
3. NIHSS on screening time point ≥ 8 points
4. Patients whose general condition was favorable enough to perform daily activities without the help of others one day prior to the ischemic stroke onset (a person with mRS 0 or 1)
5. Patients whose CTA or MRA confirmed internal carotid artery occlusion and M1 or M2 occlusion of the middle cerebral artery, that are the types of major cerebral artery occlusion that can cause acute cerebral infarction and are subject to endovascular therapy.
6. Patients with early ASPECTS point≥4 (Noncontrast brain cross-section CT or Brain cross-section MRI diffusion weighted imaging)
7. Patients who spontaneously submitted a written informed consent to participation on this clinical study.

Exclusion Criteria:

A patient who meets any one of the conditions below cannot participate in the Clinical trial.

1. Patients who meet the following exclusion criteria on imaging of endovascular therapy

   ① Patients whose occlusion location that can cause an acute ischemic stroke in the CTA (CT angiography) image meets under the following conditions: A. Occlusion of bilateral large artery B. Simultaneous infiltration of anterior and posterior circulation
2. Patients who have contraindication to contrast media for brain imaging.
3. Patients who are receiving renal replacement therapy such as dialysis due to acute or terminal nephropathy at screening point.
4. Patients who were diagnosed with cancer or received cancer therapy within 6 months at screening or have recurrent or transitional cancer.
5. Patients have high body temperature of 38oC or more and need antibiotic therapy due to medical opinion of infectious disease at screening.
6. Patients who are having pharmacotherapy due to liver diseases such as hepatic cirrhosis, etc. at screening point.
7. Patients who are pregnant or lactating. However, only a woman who has no possibility of pregnancy can participate in this clinical research.

   Woman with child-bearing potential can be defined as the woman who has not had the clear menopause or who has not had surgical treatment that makes pregnancy impossible.
8. Patients who have participated in other clinical trial within past 6 months at the screening time as a base. However, in case of participation of observatory experiment, the patient can participate in this clinical trial.
9. Patients who are determined unsuitable for participation in this clinical trial due to other reasons

Primary outcomes:
measure: mRS score evaluated at 12 week after the first dose of drug (Nelonemdaz or Placebo).
timeFrame: week12
Secondary outcomes:
measure: Proportion of mRS 0-2 evaluated at week 5 and week 12 after the first dose of drug (Nelonemdaz or Placebo).
timeFrame: week5, week12
measure: mRS score evaluated at week 5 after the first dose of investigational drug (Nelonemdaz or Placebo).
timeFrame: week5
measure: Proportion of mRS 0 measured at week 5 and week 12 after the first dose of investigational drug (Nelonemdaz or Placebo).
timeFrame: week5, week12
measure: 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)
timeFrame: 24hour(or 72hour), week5, week12
measure: 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.)
timeFrame: 24hour, week12
measure: Proportion of Barthel Index≥95 evaluated at week 5 and week 12
timeFrame: week5, week12
measure: Occurrence rate of Symptomatic intracranial hemorrhage (SICH) described and defined by this study occurring within 24 hours after the last injection
timeFrame: 24hour
Other outcomes:
measure: Proportion of adverse events and serious adverse events
timeFrame: day0~week12
measure: All mortality rate until 12 weeks
timeFrame: day0~week12
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Changwon
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daejeon
country: Korea, Republic of
facility: Daejeon Eulji Medical Center, Eulji University
city: Gwangju
country: Korea, Republic of
facility: Chosun University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Hwaseong
country: Korea, Republic of
facility: Hallym University Dongtan Sacred Heart hospital
city: Iksan
country: Korea, Republic of
facility: Wonkwang University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Jeju
country: Korea, Republic of
facility: Jeju National University Hospital
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Ewha womans University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Yongin
country: Korea, Republic of
facility: Yongin Severance Hospital
Study officials:
affiliation: Department of Neurology Asan Medical Center
name: Sun Uck Kwon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: