Ischemic StrokePhase 2SONICNCT02831088
Safety and Optimal Neuroprotection of neu2000 in Ischemic Stroke With Endovascular reCanalizion (SONIC)
A Phase 2 study testing Neu2000KWL High-does group and Neu2000KWL Low-does group in people with Ischemic Stroke, run by GNT Pharma at 6 sites in South Korea.
Trial 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 8 hours following stroke onset. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Neu2000KWL High-does group and Neu2000KWL Low-does group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 210 participants
- Where
- 6 sitesSouth Korea
- Study dates
- Jul 2016to 30 Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥19 years
- Patients who were presented to hospitals after onset of brain ischemic symptoms from the base of last normal state and can start Endovascular therapy in accordance with standard practice guidelines within 8 hours after the symptom onset.
- NIHSS scores on screening time point (admission) ≥ 8 points
- Patients whose activity is possible without the help of others in the gen-eral condition one day before the ischemic stroke onset. and whose Barthel index scores exceed 90 points
- Patients whose brain CT and CT angiography imaging confirmed acute ischemic stroke and symptomatic intracranial occlusion at screening and whose occlusion site considered the cause of acute ischemic stroke meets the following conditions:
- ① Carotid T or L type occlusion
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- ② M1 MCA
- ③ M1-MCA equivalent (two or more M2-MCAs) However, anterior temporal artery is not regarded M2
- Patients with ASPECTS on Brain CT without early imaging hyper-enhancement ≥ 6
- Patients who spontaneously submitted a written informed consent to participation on this clinical study
Who cannot join
- a medical history of hypersensitivity against aspirin (salicylates), sulfasalazine or (5-ASA) at screening.
- Patients who meets the exclusion criteria on imaging in intra-arterial re-canalization therapy ① CTA
- Patients whose imaging shows that the site of occlusion considered the cause of acute ischemic stroke meets the following conditions:
- MCA + PCA or MCA+ACA occlusion in Carotid T/L B. occlusion of a bilateral large artery C. simultaneous infiltration of anterior and posterior circulation
- ② absence of the collateral circulation corresponding to one of the followings: A. On CT angiography (MIP-CTA) imaging, absence or minimal collateral circulation at ≥50% of MCA territories, compared with pial filling of contralateral side of the lesion.
- Patients whose heart diseases corresponding to following conditions were confirmed at screening:
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- ① Patients who were diagnosed with myocardial infarction within 6 months at screening
- ② Patients who had severe arrhythmia evoking clinical symptoms (respiratory difficulties, tachycardia etc.) within 6 months at screening.
- Patients whose ECG measured at the stable state at emergency room confirmed the following results:
- pulse rate < 50 or >120 beats per minute B. 2nd or 3rd degree AV block is confirmed. C. congenital or acquired QT syndrome is confirmed D. ventricular pre-excitation syndrome is confirmed
- Patients who were diagnosed with heart failure ≥ class II according to "heart failure classification by NYHA (New York Heart Association)" before screening.
- "heart failure classification by NYHA (New York Heart Association)" Class I: patients with no limitation of activities; they suffer no symptoms from ordinary activities.
- Class II: patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion.
- Class III: patients with marked limitation of activity; they are comfortable only at rest.
- Class IV: patients who should be at complete rest, confined to bed or chair; any physical activity brings on.
- Patients who have contraindication to contrast media for brain imaging
- Patients who are receiving renal replacement therapy such as dialysis, due to acute or chronic renal failure, nephropathy, etc. at screening.
- Patients who were diagnosed with cancer or received cancer therapy within 6 months at screening or have recurrent or transitional cancer
- Patients who show high body temperature of 38℃ or more or who need antibiotic therapy due to medical opinion of infectious diseases at screening.
- Patients who take pharmacotherapy due to liver diseases such as hepatitis, liver cirrhosis etc. at screening.
- Patients who are pregnant or lactating. However, in case of a woman of child-bearing potential, only patients whose non-pregnancy was confirmed can participate in this clinical study.
- Patients who participated in other clinical studies within past 3 months at the screening time as a base. However, in case of participation in an observatory study without medication, the patients can participate in this clinical study.
- Patients who were determined unsuitable for participation in this clinical study due to other reasons.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
South Korea6 sites, 6 recruiting
- Recruiting
Chungbuk National University Hospital
Cheongju-si, 28644
- Recruiting
Keimyung University Dongsan Medical Center
Daegu, 41931
- Recruiting
Kyungpook National University Hospital
Daegu, 41944
- Recruiting
Chosun University Hospital
Gwangju, 61453
- Recruiting
Gachon University Gil Medical Center
Incheon, 21565
- Recruiting
Ajou University Hospital
Seoul, 16499
About this study
Official title: A Phase II, Double-blind, Randomized, Placebo-controlled, Multi-center Study to Assess Efficacy and Safety of Neu2000KWL in Patients With Acute Ischemic Stroke Receiving Endovascular Therapy
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 8 hours following stroke onset. Neu2000KWL will be administered before endovascular treatment.
Read the 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 8 hours of stroke onset.
- Conditions
- Ischemic Stroke
- Being tested
- Neu2000KWL High-does group, Neu2000KWL Low-does group, Placebo
- Keywords
- Neu2000KWL, Neuroprotection, endovascular therapy, glutamate, free radical
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neu2000KWL High-does groupDrug
Also called Neu2000KWL is produced by GNT Pharma Pharmaceutical company
1st infusion of 750mg in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of 500 mg at intervals of 12 hours
Neu2000KWL Low-does groupDrug
Also called Neu2000KWL is produced by GNT Pharma Pharmaceutical company
1st infusion of 500mg in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of 250 mg at intervals of 12 hours
PlaceboDrug
1st infusion of the same volume of saline in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of same volume of saline at intervals of 12 hours
| Study group | Role | What they receive |
|---|---|---|
| Neu2000KWL High-dose group | Experimental | Not described Receives: Drug: Neu2000KWL High-does group |
| Neu2000KWL Low-dose group | Experimental | Not described Receives: Drug: Neu2000KWL Low-does group |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportional Ratios of study subjects with mRS 0-2 scores at 12 weeks after Neu2000KWL treatment
Measured: 12weeks
Occurrence rate of cerebral hemorrhagic transformation occurring within 48 hours based on parenchymal hematoma (PH) criteria by ECASS (European Co-operative Acute Stroke Study)-I and II
Measured: 12weeks
Secondary outcomes (5)
Distribution changes of mRS scores at 1, 4 and 12 weeks vs baseline (shift analysis)
Measured: 1week, 4weeks, 12weeks
Ratios of NIHSS 0-2 scores at 1, 4 and 12 weeks vs baseline
Measured: 1week, 4weeks, 12weeks
Ratios of Barthel index >90 (≥ 95) at 1, 4 and 12 weeks vs baseline
Measured: 1week, 4weeks, 12weeks
Occurrence rate of cerebral hemorrhagic transformation occurring within Day 4 or Day 5 (Day of the last treatment of the study drug)
based on parenchymal hematoma (PH) criteria by ECASS (European Co-operative Acute Stroke Study)-I and II
Measured: 4-5days
Occurrence rate of symptomatic intracranial hemorrhage (SICH) described and defined by this study protocol occurring within Day 4 or Day 5 (Day of the last treatment of the study drug)
It is defined as SICH of intracranial hemorrhage by brain imaging is confirmed and any one of the following conditions is accompanied:
- in case that NIHSS scores become worse 2 points or more B. in case that NIHSS scores become worse 1 point or more, accompanying decreased consciousness C. in case that neurological deficits persist 24 hours or more (and), D. in case of recurrence of stroke and progress deterioration, or in case that other medical causes are not related.
Measured: 4-5days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2016 (estimated)
- Study startJul 2016
- Primary completion30 Dec 2018 (estimated)
- Study completion30 Dec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- GNT Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ji Man Hong, MD, PhD, Principal investigator, Ajou University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02831088
- Sponsor's protocol ID
- Neu2000KWL-P01
- Acronym
- SONIC
- Status last verified
- Dec 2016
- First submitted
- 3 Jul 2016
- Last updated
- 13 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Hong JM, Lee JS, Lee YB, Shin DH, Shin DI, Hwang YH, Ahn SH, Kim JG, Sohn SI, Kwon SU, Lee JS, Gwag BJ, Chamorro A, Choi DW; SONIC Investigators. Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial. Stroke. 2022 Nov;53(11):3250-3259. doi: 10.1161/STROKEAHA.122.039649. Epub 2022 Sep 6.
PubMed 36065810Hong JM, Choi MH, Sohn SI, Hwang YH, Ahn SH, Lee YB, Shin DI, Chamorro A, Choi DW; on the behalf of the SONIC investigators. Safety and Optimal Neuroprotection of neu2000 in acute Ischemic stroke with reCanalization: study protocol for a randomized, double-blinded, placebo-controlled, phase-II trial. Trials. 2018 Jul 13;19(1):375. doi: 10.1186/s13063-018-2746-9.
PubMed 30005644
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double-blind, Randomized, Placebo-controlled, Multi-center Study to Assess Efficacy and Safety of Neu2000KWL in Patients With Acute Ischemic Stroke Receiving Endovascular Therapy
- ClinicalTrials.gov ID
- NCT02831088
- Acronym / sponsor ID
- SONIC / Neu2000KWL-P01
- Conditions
- Ischemic Stroke
- Keywords
- Neu2000KWL, Neuroprotection, endovascular therapy, glutamate, free radical
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- GNT PharmaIndustry (pharma, biotech, devices)
- Study start
- Jul 2016
- Primary completion
- 30 Dec 2018 (estimated)
- Study completion
- 30 Dec 2018 (estimated)
- First posted
- 13 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 8 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 8 hours of stroke onset.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Neu2000KWL High-dose group | Experimental | Drug: Neu2000KWL High-does group |
| Neu2000KWL Low-dose group | Experimental | Drug: Neu2000KWL Low-does group |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults ≥19 years
- Patients who were presented to hospitals after onset of brain ischemic symptoms from the base of last normal state and can start Endovascular therapy in accordance with standard practice guidelines within 8 hours after the symptom onset.
- NIHSS scores on screening time point (admission) ≥ 8 points
- Patients whose activity is possible without the help of others in the gen-eral condition one day before the ischemic stroke onset. and whose Barthel index scores exceed 90 points
- Patients whose brain CT and CT angiography imaging confirmed acute ischemic stroke and symptomatic intracranial occlusion at screening and whose occlusion site considered the cause of acute ischemic stroke meets the following conditions:
Key exclusion criteria (23 listed)
- a medical history of hypersensitivity against aspirin (salicylates), sulfasalazine or (5-ASA) at screening.
- Patients who meets the exclusion criteria on imaging in intra-arterial re-canalization therapy ① CTA
- Patients whose imaging shows that the site of occlusion considered the cause of acute ischemic stroke meets the following conditions:
- ② absence of the collateral circulation corresponding to one of the followings: A. On CT angiography (MIP-CTA) imaging, absence or minimal collateral circulation at ≥50% of MCA territories, compared with pial filling of contralateral side of the lesion.
- Patients whose heart diseases corresponding to following conditions were confirmed at screening:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neu2000KWL High-does groupAlso: Neu2000KWL is produced by GNT Pharma Pharmaceutical company1st infusion of 750mg in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of 500 mg at intervals of 12 hours | Drug | Neu2000KWL High-dose group |
| Neu2000KWL Low-does groupAlso: Neu2000KWL is produced by GNT Pharma Pharmaceutical company1st infusion of 500mg in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of 250 mg at intervals of 12 hours | Drug | Neu2000KWL Low-dose group |
| Placebo1st infusion of the same volume of saline in patients receiving endovascular therapy within 8 hours following ischemic stroke onset followed by 9 consecutive infusions of same volume of saline at intervals of 12 hours | Drug | Placebo |
Primary outcome
Proportional Ratios of study subjects with mRS 0-2 scores at 12 weeks after Neu2000KWL treatment
Time frame: 12weeks
Occurrence rate of cerebral hemorrhagic transformation occurring within 48 hours based on parenchymal hematoma (PH) criteria by ECASS (European Co-operative Acute Stroke Study)-I and II
Time frame: 12weeks
5 secondary outcomes
Distribution changes of mRS scores at 1, 4 and 12 weeks vs baseline (shift analysis)
Time frame: 1week, 4weeks, 12weeks
Ratios of NIHSS 0-2 scores at 1, 4 and 12 weeks vs baseline
Time frame: 1week, 4weeks, 12weeks
Ratios of Barthel index >90 (≥ 95) at 1, 4 and 12 weeks vs baseline
Time frame: 1week, 4weeks, 12weeks
Occurrence rate of cerebral hemorrhagic transformation occurring within Day 4 or Day 5 (Day of the last treatment of the study drug)
Time frame: 4-5days
Occurrence rate of symptomatic intracranial hemorrhage (SICH) described and defined by this study protocol occurring within Day 4 or Day 5 (Day of the last treatment of the study drug)
Time frame: 4-5days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2017.
- Derived from this study: PubMed 36065810Hong JM, Lee JS, Lee YB, Shin DH, Shin DI, Hwang YH, Ahn SH, Kim JG, Sohn SI, Kwon SU, Lee JS, Gwag BJ, Chamorro A, Choi DW; SONIC Investigators. Nelonemdaz for Patients With Acute Ischemic Stroke Undergoing Endovascular Reperfusion Therapy: A Randomized Phase II Trial. Stroke. 2022 Nov;53(11):3250-3259. doi: 10.1161/STROKEAHA.122.039649. Epub 2022 Sep 6.
- Derived from this study: PubMed 30005644Hong JM, Choi MH, Sohn SI, Hwang YH, Ahn SH, Lee YB, Shin DI, Chamorro A, Choi DW; on the behalf of the SONIC investigators. Safety and Optimal Neuroprotection of neu2000 in acute Ischemic stroke with reCanalization: study protocol for a randomized, double-blinded, placebo-controlled, phase-II trial. Trials. 2018 Jul 13;19(1):375. doi: 10.1186/s13063-018-2746-9.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ji Man Hong, MD, PhD principal investigator
Ajou University Medical Centre
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neu2000KWL High-does group and Neu2000KWL Low-does group in people with Ischemic Stroke, run by GNT Pharma at 6 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chun San An (82-31-8005-9910, csan@gntpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportional Ratios of study subjects with mRS 0-2 scores at 12 weeks after Neu2000KWL treatment (time frame: 12weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02831088, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2017.