Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis

NCT04462536 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: NA-1-009
• Study Type: interventional
• Target: 850
• Locations: 9 countries
• Sites: 81

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).

Conditions

Stroke, Acute

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Mortality Rate, as Defined by Event Rate (Percent) for Mortality Over the 90-day Study Period.

  90 days

• Number of Participants Exhibiting a Worsening of Their Index Stroke.

  90 days

• Number of Participants With Good Neurological Outcome, as Defined by a Score of 0-2 on the NIHSS at Day 90 Post Randomization.

  90 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Vehicle only

Drug: Placebo

Nerinetide

EXPERIMENTAL

Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes

Drug: Nerinetide

Interventions

Placebo DRUG

Vehicle only

Placebo

Nerinetide DRUG

Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes

Also known as: NA-1

Nerinetide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute ischemic stroke (AIS) selected for emergency endovascular treatment.
• Age 18 years or greater.
• Onset (last-known-well) time to randomization time within 12 hours.
• Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS):
• NIHSS \> 5 for internal carotid artery (ICA) and M1-middle cerebral artery (MCA) occlusion; or
• NIHSS \> 10 for M2-MCA occlusion.
• 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.
• 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.
• Qualifying imaging performed less than 2 hours prior to randomization.
• Consent process completed as per national laws and regulation and the applicable ethics committee requirements.

You may not qualify if:

• Treated with a tissue plasminogen activator (e.g., alteplase or tenecteplase) within 24 hours before randomization.
• Determination by the treating physician, based on current treatment guidelines and medical evidence, that treatment with a plasminogen activator is indicated.
• Large core of established infarction defined as ASPECTS 0-4.
• Absent or poor collateral circulation on qualifying imaging (e.g. collateral score of 0 or 1).
• Any intracranial hemorrhage on the qualifying imaging.
• Planned use of an endovascular device not having approval or clearance by the relevant regulatory authority.
• Endovascular thrombectomy procedure is completed as defined by the presence of TICI 2c/3 reperfusion or completion of groin / arterial closure.
• 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.
• Estimated or known weight \> 120 kg (264 lbs).
• Pregnancy/Lactation; female, with positive urine or serum beta human chorionic gonadotropin (β-hCG) test, or breastfeeding.
• Known prior receipt of nerinetide for any reason, including prior enrolment in this ESCAPE-NEXT trial.
• Severe known renal impairment defined as requiring renal replacement therapy (hemo- or peritoneal dialysis).
• Severe or fatal comorbid illness that will prevent improvement or follow up.
• Inability to complete follow-up treatment to Day 90.

Sponsors & Collaborators

• NoNO Inc.: lead
• University of Calgary: collaborator

Study Sites (81)

St. Joseph's Hospital & Medical Center

Phoenix, Arizona, 85013, United States

Location

Providence Little Company of Mary Medical Center - Torrance

Torrance, California, 90503, United States

Location

Swedish Medical Center

Englewood, Colorado, 80113, United States

Location

Baptist Health Research Institute

Jacksonville, Florida, 32207, United States

Location

University of Miami, Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

NYU Langone Hospital Brooklyn

Brooklyn, New York, 11220, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

The Ohio State University, Wexner Medical Center Neurological Surgery

Columbus, Ohio, 43203, United States

Location

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

UPMC Stroke Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903-4923, United States

Location

Valley Baptist Medical Center - Harlingen

Harlingen, Texas, 78550, United States

Location

Swedish Medical Center - Cherry Hill Campus

Seattle, Washington, 98122, United States

Location

Royal Adelaide Hospital

Adelaide, Australia

Location

Princess Alexandra Hospital

Brisbane, Australia

Location

Monash Medical Centre

Clayton, Australia

Location

Gold Coast University Hospital

Gold Coast, Australia

Location

Fiona Stanley Hospital

Murdoch, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Australia

Location

John Hunter Hospital

Newcastle, Australia

Location

Royal Melbourne Hospital

Parkville, Australia

Location

Foothills Medical Centre - University of Calgary

Calgary, Alberta, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

Health Sciences Centre

Winnipeg, Manitoba, Canada

Location

Queen Elizabeth II Health Science Centre

Halifax, Nova Scotia, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Location

London Health Sciences Centre (LHSC)

London, Ontario, Canada

Location

Ottawa Hospital Research Institute (OHRI)

Ottawa, Ontario, Canada

Location

St. Michael's Hospital, Unity Health Toronto

Toronto, Ontario, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Location

Toronto Western Hospital

Toronto, Ontario, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

Location

University Hospital of Montreal

Montreal, Quebec, Canada

Location

CHU de Quebec-Universite Laval

Québec, Quebec, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Location

Universitätsklinikum RWTH Aachen

Aachen, Germany

Location

Klinikum Altenburger Land GmbH

Altenburg, Germany

Location

Universitätsklinikum Augsburg

Augsburg, Germany

Location

Universitätsklinikum Knappschaftskrankenhaus Bochum

Bochum, Germany

Location

Universitätsklinikum Bonn

Bonn, Germany

Location

Klinikum Dortmund gGmbH

Dortmund, Germany

Location

University of Dresden

Dresden, Germany

Location

Alfried-Krupp-Krankenhaus

Essen, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Göttingen University Hospital

Göttingen, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Heidelberg University Hospital

Heidelberg, Germany

Location

University Hospital Schleswig-Holstein

Kiel, Germany

Location

Universitätsklinikum Leipzig - Klinik und Poliklinik für Neurologie

Leipzig, Germany

Location

Klinikum rechts der Isar Technical University of Munich

München, Germany

Location

LMU Klinikum München

München, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Nürnberg Hospital South Campus

Nuremberg, Germany

Location

Evangelisches Krankenhaus Oldenburg

Oldenburg, Germany

Location

Klinikum Stuttgart

Stuttgart, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Würzburg University Hospital

Würzburg, Germany

Location

Ospedale Maggiore di Bologna "Carlo Alberto Pizzardi"

Bologna, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

Location

Ospedale Policlinico San Martino

Genoa, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Azienda Ospedaliera Antonio Cardarelli

Napoli, Italy

Location

Amsterdam UMC

Amsterdam, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Erasmus University Medical Center

Rotterdam, Netherlands

Location

Oslo University Hospital Rikshospitalet

Oslo, Norway

Location

Oslo University Hospital Ulleval

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

University Hospital of North-Norway

Tromsø, Norway

Location

National Neuroscience Institute

Singapore, Singapore

Location

National University Hospital

Singapore, Singapore

Location

Kantonsspital Aarau

Aarau, Switzerland

Location

Universitätsspital Basel

Basel, Switzerland

Location

Universitatsklinik fur Neurologie, Inselspital

Bern, Switzerland

Location

Related Publications (1)

• Hill MD, Goyal M, Demchuk AM, Menon BK, Field TS, Guest WC, Berrouschot J, Bormann A, Pham M, Haeusler KG, Dippel DWJ, van Doormaal PJ, Dorn F, Bode FJ, van Adel BA, Sahlas DJ, Swartz RH, Da Costa L, Ospel JM, McDonough RV, Ryckborst KJ, Almekhlafi MA, Heard KJ, Garman DJ, Adams C, Kohli Y, Schoon BA, Buck BH, Muto M, Zafar A, Schneider H, Grossberg JA, Yeo LLL, Tarpley JW, Psychogios MN, Coutinho JM, Limbucci N, Puetz V, Kelly ME, Campbell BCV, Poli S, Poppe AY, Shankar JJ, Chandra R, Dowlatshahi D, Lopez GA, Cirillo L, Moussaddy A, Devlin M, Garcia-Bermejo P, Mandzia JL, Skjelland M, Aamodt AH, Silver FL, Kleinig TJ, Pero G, Minnerup J, McTaggart RA, Puri AS, Chiu AHY, Reimann G, Gubitz GJ, Camden MC, Lee SK, Sauvageau E, Mundiyanapurath S, Frei DF, Choe H, Rocha M, Gralla J, Bailey P, Fischer S, Liebig T, Dimitriadis K, Gandhi D, Chapot R, Jin A, Hassan AE, Zwam WV, Maier IL, Wiesmann M, Niesen WD, Advani R, Eltoft A, Asdaghi N, Murphy C, Remonda L, Ghia D, Jansen O, Holtmannspoetter M, Hellstern V, Witt K, Fromme A, Nimjee SM, Turkel-Parella D, Michalski D, Maegerlein C, Tham CH, Tymianski M; ESCAPE-NEXT Investigators. Efficacy and safety of nerinetide in acute ischaemic stroke in patients undergoing endovascular thrombectomy without previous thrombolysis (ESCAPE-NEXT): a multicentre, double-blind, randomised controlled trial. Lancet. 2025 Feb 15;405(10478):560-570. doi: 10.1016/S0140-6736(25)00194-1.

  PMID: 39955119 DERIVED

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Michael Tymianski
• Organization: NoNO Inc.

mtymianski@nonoinc.ca

6472932232

Study Officials

• Michael D. Hill, MD MSc

  Study Principal Investigator, University of Calgary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 8, 2020
• Study Start: December 6, 2020
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: June 22, 2025
• Results First Posted: June 22, 2025

Record last verified: 2023-09

Locations

NO (4); IT (5); CA (16); DE (23); NL (3); AU (8); US (17); CH (3); SG (2)