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

NCT ID: NCT04462536

Last Updated: 2025-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 850 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-06
• Study Completion Date: 2023-08-31

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.

Conditions

Stroke, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Vehicle only

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Vehicle only

Nerinetide

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

Group Type: EXPERIMENTAL

Nerinetide

Intervention Type: DRUG

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

Interventions

Placebo

Vehicle only

Intervention Type: DRUG

Nerinetide

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

Intervention Type: DRUG

Other Intervention Names

NA-1

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: collaborator

NoNO Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael D. Hill, MD MSc

Role: PRINCIPAL_INVESTIGATOR

Study Principal Investigator, University of Calgary

Locations

St. Joseph's Hospital & Medical Center

Phoenix, Arizona, United States

Providence Little Company of Mary Medical Center - Torrance

Torrance, California, United States

Swedish Medical Center

Englewood, Colorado, United States

Baptist Health Research Institute

Jacksonville, Florida, United States

University of Miami, Jackson Memorial Hospital

Miami, Florida, United States

Grady Memorial Hospital

Atlanta, Georgia, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

NYU Langone Hospital Brooklyn

Brooklyn, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

The Ohio State University, Wexner Medical Center Neurological Surgery

Columbus, Ohio, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

UPMC Stroke Institute

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Valley Baptist Medical Center - Harlingen

Harlingen, Texas, United States

Swedish Medical Center - Cherry Hill Campus

Seattle, Washington, United States

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, , Australia

Foothills Medical Centre - University of Calgary

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Health Sciences Centre

Winnipeg, Manitoba, 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

Ottawa Hospital Research Institute (OHRI)

Ottawa, Ontario, Canada

St. Michael's Hospital, Unity Health Toronto

Toronto, Ontario, Canada

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Toronto Western Hospital

Toronto, Ontario, Canada

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

University Hospital of Montreal

Montreal, Quebec, Canada

CHU de Quebec-Universite Laval

Québec, Quebec, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

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 im Breisgau, , 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

Nuremberg, , Germany

Evangelisches Krankenhaus Oldenburg

Oldenburg, , Germany

Klinikum Stuttgart

Stuttgart, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Würzburg University Hospital

Würzburg, , Germany

Ospedale Maggiore di Bologna "Carlo Alberto Pizzardi"

Bologna, , Italy

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Ospedale Policlinico San Martino

Genoa, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliera Antonio Cardarelli

Napoli, , Italy

Amsterdam UMC

Amsterdam, , Netherlands

Maastricht University Medical Center

Maastricht, , Netherlands

Erasmus University Medical Center

Rotterdam, , Netherlands

Oslo University Hospital Rikshospitalet

Oslo, , Norway

Oslo University Hospital Ulleval

Oslo, , Norway

Stavanger University Hospital

Stavanger, , Norway

University Hospital of North-Norway

Tromsø, , Norway

National Neuroscience Institute

Singapore, , Singapore

National University Hospital

Singapore, , Singapore

Kantonsspital Aarau

Aarau, , Switzerland

Universitätsspital Basel

Basel, , Switzerland

Universitatsklinik fur Neurologie, Inselspital

Bern, , Switzerland

Countries

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

References

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.

Reference Type: DERIVED

PMID: 39955119 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NA-1-009

Identifier Type: -

Identifier Source: org_study_id