Clinical trial NCT04462536: Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis
Official title: A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stroke, Acute
Lead sponsor: NoNO Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Calgary
First posted: 2020-07-08
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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 (β-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.

Primary outcomes:
measure: Number of participants with independent functioning on the modified Rankin Scale (mRS), as defined by a score of 0-2
timeFrame: 90 days
Secondary outcomes:
measure: Mortality rate, as defined by event rate (percent) for mortality over the 90-day study period.
timeFrame: 90 days
measure: Number of participants exhibiting a worsening of their index stroke.
timeFrame: 90 days
measure: 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.
timeFrame: 90 days
measure: Number of participants with good neurological outcome, as defined by a score of 0-2 on the NIHSS at Day 90 post randomization.
timeFrame: 90 days
Other outcomes:
measure: Volume of stroke as measured by MRI or CT brain imaging (MRI preferred)
timeFrame: 90 days
measure: 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.
timeFrame: 90 days
measure: 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.
timeFrame: 90 days
measure: Number of participants with excellent functional outcome, as defined by a score of 0-1 on the mRS at Day 90 post randomization.
timeFrame: 90 days
measure: Health-related quality of life, as measured by the EQ-5D-5L at Day 90.
timeFrame: 90 days
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital & Medical Center
state: Arizona
city: Torrance
country: United States
facility: Providence Little Company of Mary Medical Center - Torrance
state: California
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Jacksonville
country: United States
facility: Baptist Health Research Institute
state: Florida
city: Miami
country: United States
facility: University of Miami, Jackson Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: NYU Langone Hospital Brooklyn
state: New York
city: Columbus
country: United States
facility: The Ohio State University, Wexner Medical Center Neurological Surgery
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Stroke Institute
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Harlingen
country: United States
facility: Valley Baptist Medical Center - Harlingen
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center - Cherry Hill Campus
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: Newcastle
country: Australia
facility: John Hunter Hospital
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Calgary
country: Canada
facility: Foothills Medical Centre - University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre (LHSC)
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute (OHRI)
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital, Unity Health Toronto
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Montreal
country: Canada
facility: University Hospital of Montreal
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec-Universite Laval
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Aachen
country: Germany
facility: Universitätsklinikum RWTH Aachen
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land GmbH
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Bochum
country: Germany
facility: Universitätsklinikum Knappschaftskrankenhaus Bochum
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Dresden
country: Germany
facility: University of Dresden
city: Essen
country: Germany
facility: Alfried-Krupp-Krankenhaus
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Göttingen
country: Germany
facility: Göttingen University Hospital
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig - Klinik und Poliklinik für Neurologie
city: München
country: Germany
facility: Klinikum rechts der Isar Technical University of Munich
city: München
country: Germany
facility: LMU Klinikum München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Nürnberg
country: Germany
facility: Nürnberg Hospital South Campus
city: Oldenburg
country: Germany
facility: Evangelisches Krankenhaus Oldenburg
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Würzburg
country: Germany
facility: Würzburg University Hospital
city: Bologna
country: Italy
facility: Ospedale Maggiore di Bologna "Carlo Alberto Pizzardi"
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Genoa
country: Italy
facility: Ospedale Policlinico San Martino
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Azienda Ospedaliera Antonio Cardarelli
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Oslo
country: Norway
facility: Oslo University Hospital Rikshospitalet
city: Oslo
country: Norway
facility: Oslo University Hospital Ulleval
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North-Norway
city: Singapore
country: Singapore
facility: National Neuroscience Institute
city: Singapore
country: Singapore
facility: National University Hospital
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Universitatsklinik fur Neurologie, Inselspital
Study officials:
affiliation: Study Principal Investigator, University of Calgary
name: Michael D. Hill, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: