Rescues On Reperfusion Damage In Cerebral Infarction by Nelonemdaz (RODIN)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Neu2000KWL group; Drug: Placebo group

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.

• Study Type: Interventional
• Enrollment (Anticipated): 496
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chun San An; Phone Number: 82-31-8005-9910; Email: csan@gntpharma.com

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Recruiting
    • Dong-A University Hospital
    • Principal Investigator: Jae Gwan Cha
  • Busan, Korea, Republic of, 47392
    • Recruiting
    • Inje University Busan Paik Hospital
    • Principal Investigator: Eung Gyu Kim
  • Changwon, Korea, Republic of, 52727
    • Recruiting
    • Gyeongsang National University Hospital
    • Principal Investigator: Soo Kyoung Kim
  • Cheongju-si, Korea, Republic of, 28644
    • Recruiting
    • Chungbuk National University Hospital
    • Principal Investigator: Dong Ick Shin
  • Daegu, Korea, Republic of, 42601
    • Recruiting
    • Keimyung University Dongsan Medical Center
    • Principal Investigator: Sung Il Sohn
  • Daegu, Korea, Republic of, 41944
    • Recruiting
    • Kyungpook National University Hospital
    • Principal Investigator: Yang Ha Hwang
  • Daejeon, Korea, Republic of, 35233
    • Recruiting
    • Daejeon Eulji Medical Center, Eulji University
    • Principal Investigator: Jae Kook Kim
  • Gwangju, Korea, Republic of, 61469
    • Recruiting
    • Chonnam National University Hospital
    • Principal Investigator: Man Seok Park
  • Gwangju, Korea, Republic of, 61453
    • Recruiting
    • Chosun University Hospital
    • Principal Investigator: Seong Hwan Ahn
  • Hwaseong, Korea, Republic of, 18450
    • Not yet recruiting
    • Hallym University Dongtan Sacred Heart Hospital
    • Principal Investigator: Hee Jung Mo
  • Iksan, Korea, Republic of, 54538
    • Not yet recruiting
    • Wonkwang University Hospital
    • Principal Investigator: Young Seo Kim
  • Incheon, Korea, Republic of, 21565
    • Recruiting
    • Gachon University Gil Medical Center
    • Principal Investigator: Young Bae Lee
  • Incheon, Korea, Republic of, 22332
    • Not yet recruiting
    • Inha University Hospital
    • Principal Investigator: Hee Kwon Park
  • Jeju, Korea, Republic of, 63241
    • Recruiting
    • Jeju National University Hospital
    • Principal Investigator: Jae Chul Choi
  • Jeonju, Korea, Republic of, 54907
    • Recruiting
    • Jeonbuk National University Hospital
    • Principal Investigator: Hyun Gu Kang
  • Seongnam, Korea, Republic of, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
    • Principal Investigator: Hee Jun Bae
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Principal Investigator: Keun Hwa Jung
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Principal Investigator: Sun Uck Kwon
  • Seoul, Korea, Republic of, 02447
    • Recruiting
    • KyungHee University Medical Center
    • Principal Investigator: Seong Hyuk Huh
  • Seoul, Korea, Republic of, 02841
    • Recruiting
    • Korea University Anam Hospital
    • Principal Investigator: Seong Wook Yoo
  • Seoul, Korea, Republic of, 07804
    • Recruiting
    • Ewha Womans University Seoul Hospital
    • Principal Investigator: Tae Jin Song
  • Seoul, Korea, Republic of, 16499
    • Recruiting
    • Samsung Medical Center
    • Principal Investigator: Woo Keun Seo
  • Ulsan, Korea, Republic of, 44033
    • Recruiting
    • Ulsan University Hospital
    • Principal Investigator: Ji Hyun Kwon
  • Yongin, Korea, Republic of, 16995
    • Recruiting
    • Yongin Severance Hospital
    • Principal Investigator: Jin Kwon Kim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo group; 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
Experimental: Neu2000KWL	Drug: Neu2000KWL group; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mRS score evaluated at 12 week after the first dose of drug (Nelonemdaz or Placebo).	week12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of mRS 0-2 evaluated at week 5 and week 12 after the first dose of drug (Nelonemdaz or Placebo).		week5, week12
mRS score evaluated at week 5 after the first dose of investigational drug (Nelonemdaz or Placebo).		week5
Proportion of mRS 0 measured at week 5 and week 12 after the first dose of investigational drug (Nelonemdaz or Placebo).		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)		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.)		24hour, week12
Proportion of Barthel Index≥95 evaluated at week 5 and week 12		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)	24hour

Other Outcome Measures

Outcome Measure	Time Frame
Proportion of adverse events and serious adverse events	day0~week12
All mortality rate until 12 weeks	day0~week12

Collaborators and Investigators

• Sponsor: GNT Pharma
• Investigators: Principal Investigator: Sun Uck Kwon, MD, PhD, Department of Neurology Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2021
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 10, 2021

Study Record Updates

• Last Update Posted (Actual): September 26, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Neuroprotection; glutamate; Neu2000KWL; endovascular therapy; free radical
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: Neu2000KWL-P03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No