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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04462536
Other study ID # NA-1-009
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date December 6, 2020
Est. completion date August 31, 2023

Study information

Verified date September 2023
Source NoNO Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary purpose of this study is to determine if a single dose of nerinetide can reduce global disability in people who have had a stroke and are selected for endovascular therapy without the use of a tissue plasminogen activator (alteplase, tenecteplase, or equivalent).


Description:

This study is a Phase 3, randomized, multicentre, blinded, placebo-controlled, parallel group, single-dose with a single interim analysis. Because AIS (acute ischemic stroke) is a medical emergency, the trial is designed to enable the administration of standard-of-care treatments without delay in order to save the life of the person concerned, restore good health or alleviate suffering. Participants harboring an acute ischemic stroke who are selected for endovascular revascularization without intravenous or intra-arterial thrombolytic therapy will be given a single, 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous dose of nerinetide or placebo. Outcomes of the main trial will be evaluated throughout a 90 day observation period. Participants will be followed at 1-Year for the analytic sub-trial for further outcome assessment by telemedicine or telephone interview conducted by individuals blinded to the outcome of the main trial. This sub-trial will be conducted to explore the independent functioning and quality of life at 1-Year.


Recruitment information / eligibility

Status Completed
Enrollment 850
Est. completion date August 31, 2023
Est. primary completion date August 31, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Acute ischemic stroke (AIS) selected for emergency endovascular treatment. 2. Age 18 years or greater. 3. Onset (last-known-well) time to randomization time within 12 hours. 4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS): 1. NIHSS > 5 for internal carotid artery (ICA) and M1-middle cerebral artery (MCA) occlusion; or 2. NIHSS > 10 for M2-MCA occlusion. 5. Confirmed symptomatic intracranial occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA. Tandem extracranial carotid and intracranial occlusions are permitted. 6. Pre-stroke (24 hours prior to stroke onset) independent functional status in activities of daily living with modified Barthel Index (BI) = 95. Patient must be living without requiring nursing care. 7. Qualifying imaging performed less than 2 hours prior to randomization. 8. Consent process completed as per national laws and regulation and the applicable ethics committee requirements. Exclusion Criteria: 1. Treated with a tissue plasminogen activator (e.g., alteplase or tenecteplase) within 24 hours before randomization. 2. Determination by the treating physician, based on current treatment guidelines and medical evidence, that treatment with a plasminogen activator is indicated. 3. Large core of established infarction defined as ASPECTS 0-4. 4. Absent or poor collateral circulation on qualifying imaging (e.g. collateral score of 0 or 1). 5. Any intracranial hemorrhage on the qualifying imaging. 6. Planned use of an endovascular device not having approval or clearance by the relevant regulatory authority. 7. Endovascular thrombectomy procedure is completed as defined by the presence of TICI 2c/3 reperfusion or completion of groin / arterial closure. 8. Clinical history, past imaging or clinical judgment suggesting that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention. 9. Estimated or known weight > 120 kg (264 lbs). 10. Pregnancy/Lactation; female, with positive urine or serum beta human chorionic gonadotropin (ß-hCG) test, or breastfeeding. 11. Known prior receipt of nerinetide for any reason, including prior enrolment in this ESCAPE-NEXT trial. 12. Severe known renal impairment defined as requiring renal replacement therapy (hemo- or peritoneal dialysis). 13. Severe or fatal comorbid illness that will prevent improvement or follow up. 14. Inability to complete follow-up treatment to Day 90. 15. Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding trial inclusion.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Placebo
Vehicle only
Nerinetide
Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes

Locations

Country Name City State
Australia Royal Adelaide Hospital Adelaide
Australia Princess Alexandra Hospital Brisbane
Australia Monash Medical Centre Clayton
Australia Gold Coast University Hospital Gold Coast
Australia Fiona Stanley Hospital Murdoch
Australia Sir Charles Gairdner Hospital Nedlands
Australia John Hunter Hospital Newcastle
Australia Royal Melbourne Hospital Parkville
Canada Foothills Medical Centre - University of Calgary Calgary Alberta
Canada University of Alberta Hospital Edmonton Alberta
Canada Queen Elizabeth II Health Science Centre Halifax Nova Scotia
Canada Hamilton Health Sciences Hamilton Ontario
Canada Kingston Health Sciences Centre Kingston Ontario
Canada London Health Sciences Centre (LHSC) London Ontario
Canada Montreal Neurological Institute and Hospital Montreal Quebec
Canada University Hospital of Montreal Montreal Quebec
Canada Ottawa Hospital Research Institute (OHRI) Ottawa Ontario
Canada CHU de Quebec-Universite Laval Quebec City Quebec
Canada Royal University Hospital Saskatoon Saskatchewan
Canada St. Michael's Hospital, Unity Health Toronto Toronto Ontario
Canada Sunnybrook Health Science Centre Toronto Ontario
Canada Toronto Western Hospital Toronto Ontario
Canada Vancouver General Hospital Vancouver British Columbia
Canada Health Sciences Centre Winnipeg Manitoba
Germany Universitätsklinikum RWTH Aachen Aachen
Germany Klinikum Altenburger Land GmbH Altenburg
Germany Universitätsklinikum Augsburg Augsburg
Germany Universitätsklinikum Knappschaftskrankenhaus Bochum Bochum
Germany Universitätsklinikum Bonn Bonn
Germany Klinikum Dortmund gGmbH Dortmund
Germany University of Dresden Dresden
Germany Alfried-Krupp-Krankenhaus Essen
Germany Universitätsklinikum Frankfurt Frankfurt
Germany Universitätsklinikum Freiburg Freiburg
Germany Göttingen University Hospital Göttingen
Germany Universitätsklinikum Hamburg-Eppendorf Hamburg
Germany Heidelberg University Hospital Heidelberg
Germany University Hospital Schleswig-Holstein Kiel
Germany Universitätsklinikum Leipzig - Klinik und Poliklinik für Neurologie Leipzig
Germany Klinikum rechts der Isar Technical University of Munich München
Germany LMU Klinikum München München
Germany Universitätsklinikum Münster Münster
Germany Nürnberg Hospital South Campus Nürnberg
Germany Evangelisches Krankenhaus Oldenburg Oldenburg
Germany Klinikum Stuttgart Stuttgart
Germany Universitätsklinikum Tübingen Tübingen
Germany Würzburg University Hospital Würzburg
Italy Ospedale Maggiore di Bologna "Carlo Alberto Pizzardi" Bologna
Italy Azienda Ospedaliero Universitaria Careggi Firenze
Italy Ospedale Policlinico San Martino Genoa
Italy ASST Grande Ospedale Metropolitano Niguarda Milan
Italy Azienda Ospedaliera Antonio Cardarelli Napoli
Netherlands Amsterdam UMC Amsterdam
Netherlands Maastricht University Medical Center Maastricht
Netherlands Erasmus University Medical Center Rotterdam
Norway Oslo University Hospital Rikshospitalet Oslo
Norway Oslo University Hospital Ulleval Oslo
Norway Stavanger University Hospital Stavanger
Norway University Hospital of North-Norway Tromsø
Singapore National Neuroscience Institute Singapore
Singapore National University Hospital Singapore
Switzerland Kantonsspital Aarau Aarau
Switzerland Universitätsspital Basel Basel
Switzerland Universitatsklinik fur Neurologie, Inselspital Bern
United States Abington Memorial Hospital Abington Pennsylvania
United States Grady Memorial Hospital Atlanta Georgia
United States University of Maryland Medical Center Baltimore Maryland
United States Montefiore Medical Center Bronx New York
United States NYU Langone Hospital Brooklyn Brooklyn New York
United States The Ohio State University, Wexner Medical Center Neurological Surgery Columbus Ohio
United States Swedish Medical Center Englewood Colorado
United States Valley Baptist Medical Center - Harlingen Harlingen Texas
United States Baptist Health Research Institute Jacksonville Florida
United States University of Miami, Jackson Memorial Hospital Miami Florida
United States St. Joseph's Hospital & Medical Center Phoenix Arizona
United States UPMC Stroke Institute Pittsburgh Pennsylvania
United States Providence St. Vincent Medical Center Portland Oregon
United States Rhode Island Hospital Providence Rhode Island
United States Swedish Medical Center - Cherry Hill Campus Seattle Washington
United States Providence Little Company of Mary Medical Center - Torrance Torrance California
United States University of Massachusetts Medical School Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
NoNO Inc. University of Calgary

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Italy,  Netherlands,  Norway,  Singapore,  Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Other Volume of stroke as measured by MRI or CT brain imaging (MRI preferred) 90 days
Other Number of participants with functional independence in activities of daily living, as defined by a score of = 95 on the Barthel Index (BI) at Day 90 post randomization. The BI is an index of functional independence that is a valid measure of activities of daily living when employed in stroke trials. Modified BI scores range from 0 to 100, with higher scores indicating greater independence in activities of daily living and mobility. 90 days
Other Number of participants with reduced moderate or severe disability or death, as defined by a score of 4-6 on the mRS at Day 90 post randomization. The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death. 90 days
Other Number of participants with excellent functional outcome, as defined by a score of 0-1 on the mRS at Day 90 post randomization. The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death. 90 days
Other Health-related quality of life, as measured by the EQ-5D-5L at Day 90. The EQ-5D-5L (EuroQol 5-Dimensional 5-Level) is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The respondents will also rate their overall health on the day of the interview on a 0-100 visual analogue scale (EQ-VAS, higher scores mean better outcomes). 90 days
Primary Number of participants with independent functioning on the modified Rankin Scale (mRS), as defined by a score of 0-2 The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death. 90 days
Secondary Mortality rate, as defined by event rate (percent) for mortality over the 90-day study period. 90 days
Secondary Number of participants exhibiting a worsening of their index stroke. Worsening of stroke is defined as (A) progression, or hemorrhagic transformation of the index stroke, as documented by medical imaging that is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a =4 point increase from lowest NIHSS during hospitalization or (B) results in death from the index stroke. 90 days
Secondary A shift of one or more categories to reduced functional dependence analyzed across the whole distribution of outcomes on the mRS at Day 90 post randomization. The modified Rankin Scale (mRS) is a valid and reliable clinician-reported measure of global disability that has been widely applied for evaluating recovery from stroke. It is a scale used to measure functional recovery (the degree of disability or dependence in daily activities) of people who have suffered a stroke. mRS scores range from 0 (best outcome) to 6 (worst outcome), with 0 indicating no residual symptoms; 5 indicating bedbound, requiring constant care; and 6 indicating death. 90 days
Secondary Number of participants with good neurological outcome, as defined by a score of 0-2 on the NIHSS at Day 90 post randomization. The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity. 90 days
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