Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke

NCT02930018 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: NA-1-007
• Study Type: interventional
• Target: 1,105
• Locations: 8 countries
• Sites: 50

Brief Summary

The ESCAPE-NA-1 study is designed to determine the safety and efficacy of the neuroprotectant, Nerinetide (NA-1), in reducing global disability in subjects with major acute ischemic stroke (AIS) with a small established infarct core and with good collateral circulation who are selected for endovascular revascularization.

Conditions

Stroke, Acute

Keywords

Acute Ischemic Stroke; Endovascular Thrombectomy; Neuroprotection; Tat-NR2B9c; NA-1; Nerinetide

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With mRS Score of 0 to 2

  Overall number of subjects experiencing a favorable functional outcome 90 days post-randomization, defined as 0 to 2 on the mRS. 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 (2)

• Number of Subjects With NIHSS Score of 0 to 2

  90 Days or the last rating

• Mortality Rate

  90 Days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug vehicle only

Drug: Placebo

Nerinetide (NA-1), 2.6 mg/kg

EXPERIMENTAL

Drug: Nerinetide (NA-1), 2.6 mg/kg

Interventions

Nerinetide (NA-1), 2.6 mg/kg DRUG

Single intravenous infusion of nerinetide over 10 ± 1 minutes

Also known as: NA-1

Nerinetide (NA-1), 2.6 mg/kg

Placebo DRUG

Placebo Comparator: Placebo

Also known as: Drug vehicle only

Placebo

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) for immediate endovascular treatment
• Age 18 or greater.
• Onset (last-seen-well) time to randomization time within 12 hours.
• Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS) \> 5 at the time of randomization.
• Pre-stroke (24 hours prior to stroke onset) independent functional status in activities of daily living with modified Barthel Index (BI) \> 90 (95 or 100). Patient must be living in their own home, apartment or seniors lodge where no nursing care is required.
• Confirmed symptomatic intracranial occlusion, based on multiphase or dynamic computerized tomographic angiography (CTA), at one or more of the following locations: Intracranial carotid T/L, M1 middle cerebral artery (MCA). Functionally, when defining the M1 or the M2, the bulk of the MCA territory must be ischemic.
• Non-contrast computed tomography (NCCT) and CTA (multiphase or dynamic) for trial eligibility performed or repeated at ESCAPE-NA1 stroke centre with endovascular suite on-site.
• Endovascular treatment with declared first endovascular approach as either stent retriever or aspiration device, and intended to be initiated (arterial access) within 60 minutes of baseline/qualifying NCCT and to first recanalization of 90 minutes. Study drug intended to be administered within 60 minutes of the baseline/qualifying NCCT.

You may not qualify if:

• Evidence of a large core of established infarction defined as ASPECTS 0-4.
• Evidence of absence of collateral circulation on CTA (Collateral score of 0 or 1).
• Intent to use any endovascular device other than a stent retriever or clot aspiration device or intra-arterial medications as the initial thrombectomy approach.
• Intent to use any intravenous thrombolytic other than alteplase if intravenous thrombolysis is planned.
• No femoral pulses, very difficult endovascular access or extreme tortuosity of great vessels that is predicted to result in an inability to deliver timely endovascular therapy. Direct common carotid or radial/brachial/axillary access is permissible.
• Estimated or known weight \> 120 kg or \< 45 kg.
• Pregnancy; if a woman is of childbearing potential a urine or serum beta human chorionic gonadotropin (β-hCG) test is positive, or breastfeeding.
• Severe contrast allergy or absolute contraindication to iodinated contrast preventing endovascular intervention, including any contraindications listed in the prescribing information approved by local authorities (e.g., patients with decompensated heart failure as a contraindication for the use of VISIPAQUE™ 270 in Germany).
• Clinical history, past imaging or clinical judgment suggests that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention.
• Prior enrolment in the ESCAPE-NA1 trial or prior receipt of NA-1 for any reason.
• Severe known renal impairment defined as requiring dialysis (hemo- or peritoneal) or if known a creatinine clearance \< 29 mL/min.
• Patient has a severe or fatal comorbid illness that will prevent improvement or follow-up.
• Patient cannot complete follow-up treatment due to co-morbid non-fatal illness or they are known to be a visitor to the city or any other known reason for which follow-up would be impossible (e.g. incarcerated in a federal prison).

Sponsors & Collaborators

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

Study Sites (50)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

California Pacific Medical Center - Davies Campus

San Francisco, California, 94114, United States

Location

Providence Little Company of Mary Medical Center Torrance

Torrance, California, 90503, United States

Location

Swedish Medical Center

Englewood, Colorado, 80110, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Baptist Health Medical Center

Jacksonville, Florida, 32207, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

WellStar Health Systems

Marietta, Georgia, 30060, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

NYU Lutheran Medical Center

Brooklyn, New York, 11220, United States

Location

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Riverside Radiology

Columbus, Ohio, 43214, United States

Location

Abington Memorial Hospital

Philadelphia, Pennsylvania, 19001, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37403, United States

Location

Valley Baptist Medical Center

Harlingen, Texas, 78550, United States

Location

Swedish Medical Center- Cherry Hill Campus

Seattle, Washington, 98122, United States

Location

Royal Adelaide Hospital

Adelaide, Australia

Location

Royal Melbourne Hospital

Parkville, Australia

Location

University of Calgary - Foothills Medical Centre

Calgary, Alberta, T2N2T9, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Vancouver Stroke Program Research Office/ Vancouver General Hosptial

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Queen Elizabeth II Health Science Centre

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

London Health Sciences Centre- University Hospital

London, Ontario, N6A 5A5, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

Location

Sunnybrook Health Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

CHUM Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Montreal Neurological Institute and Hospital

Montreal, Quebec, H3A1A1, Canada

Location

CHU de Quebec- Universite Laval- Hopital de l'Enfant-Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Universitätsklinikum Carl Gustav Carus Dresdner Neurovaskulares Centrum

Dresden, 01307, Germany

Location

Klinik für Radiologie und Neuroradiologie

Essen, D - 45131, Germany

Location

University Medical Center Goettingen

Göttingen, 37075, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Neurologische Klinik, Universität Heidelberg

Heidelberg, 69120, Germany

Location

Beaumont Hospital

Dublin, Ireland

Location

Mater Hospital

Dublin, Ireland

Location

Dongsan Medical Centre

Daegu, South Korea

Location

Inha University Hospital

Incheon, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Yonsei Univ, Severence

Seoul, South Korea

Location

Skåne University Hospital

Lund, Sweden

Location

Karolinksa Institutet

Stockholm, 17176, Sweden

Location

Royal Victoria Hospital

Belfast, United Kingdom

Location

Related Publications (14)

• Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrugge KG, Milot G, Clark WM, Macdonald RL, Kelly ME, Boulton M, Fleetwood I, McDougall C, Gunnarsson T, Chow M, Lum C, Dodd R, Poublanc J, Krings T, Demchuk AM, Goyal M, Anderson R, Bishop J, Garman D, Tymianski M; ENACT trial investigators. Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2012 Nov;11(11):942-50. doi: 10.1016/S1474-4422(12)70225-9. Epub 2012 Oct 8.

  PMID: 23051991 BACKGROUND

• Cook DJ, Teves L, Tymianski M. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature. 2012 Feb 29;483(7388):213-7. doi: 10.1038/nature10841.

  PMID: 22388811 BACKGROUND

• Cook DJ, Teves L, Tymianski M. A translational paradigm for the preclinical evaluation of the stroke neuroprotectant Tat-NR2B9c in gyrencephalic nonhuman primates. Sci Transl Med. 2012 Oct 3;4(154):154ra133. doi: 10.1126/scitranslmed.3003824.

  PMID: 23035045 BACKGROUND

• Sun HS, Doucette TA, Liu Y, Fang Y, Teves L, Aarts M, Ryan CL, Bernard PB, Lau A, Forder JP, Salter MW, Wang YT, Tasker RA, Tymianski M. Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat. Stroke. 2008 Sep;39(9):2544-53. doi: 10.1161/STROKEAHA.107.506048. Epub 2008 Jul 10.

  PMID: 18617669 BACKGROUND

• Aarts M, Liu Y, Liu L, Besshoh S, Arundine M, Gurd JW, Wang YT, Salter MW, Tymianski M. Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions. Science. 2002 Oct 25;298(5594):846-50. doi: 10.1126/science.1072873.

  PMID: 12399596 BACKGROUND

• Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science. 1999 Jun 11;284(5421):1845-8. doi: 10.1126/science.284.5421.1845.

  PMID: 10364559 BACKGROUND

• Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.

  PMID: 25671798 BACKGROUND

• Hill MD, Goyal M, Menon BK, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Buck BH, Field TS, Dowlatshahi D, van Adel BA, Swartz RH, Shah RA, Sauvageau E, Zerna C, Ospel JM, Joshi M, Almekhlafi MA, Ryckborst KJ, Lowerison MW, Heard K, Garman D, Haussen D, Cutting SM, Coutts SB, Roy D, Rempel JL, Rohr AC, Iancu D, Sahlas DJ, Yu AYX, Devlin TG, Hanel RA, Puetz V, Silver FL, Campbell BCV, Chapot R, Teitelbaum J, Mandzia JL, Kleinig TJ, Turkel-Parrella D, Heck D, Kelly ME, Bharatha A, Bang OY, Jadhav A, Gupta R, Frei DF, Tarpley JW, McDougall CG, Holmin S, Rha JH, Puri AS, Camden MC, Thomalla G, Choe H, Phillips SJ, Schindler JL, Thornton J, Nagel S, Heo JH, Sohn SI, Psychogios MN, Budzik RF, Starkman S, Martin CO, Burns PA, Murphy S, Lopez GA, English J, Tymianski M; ESCAPE-NA1 Investigators. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. Lancet. 2020 Mar 14;395(10227):878-887. doi: 10.1016/S0140-6736(20)30258-0. Epub 2020 Feb 20.

  PMID: 32087818 RESULT

• Stebner A, Bosshart SL, Fujiwara S, Frei D, Tarpley J, Dowlatshahi D, Rempel JL, Hill MD, Goyal M, Ospel JM; ESCAPE-NA1 Investigators. Association of baseline infarct size, reperfusion grade and intracranial hemorrhage in patients undergoing thrombectomy. J Neurointerv Surg. 2025 Mar 23:jnis-2025-023103. doi: 10.1136/jnis-2025-023103. Online ahead of print.

  PMID: 40122606 DERIVED

• Ospel JM, Goyal M, Menon BK, Almekhlafi MA, Zerna C, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Rempel JL, Joshi M, Kashani N, Heard K, Field TS, Dowlatshahi D, van Adel B, Swartz RH, Shah R, Sauvageau E, Puetz V, Silver FL, Campbell B, Chapot R, Tymianski M, Hill MD; ESCAPE-NA1 Investigators. Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial. Stroke. 2025 Jan;56(1):14-21. doi: 10.1161/STROKEAHA.124.048601. Epub 2024 Dec 9.

  PMID: 39648909 DERIVED

• Ospel JM, Rex N, Rinkel L, Kashani N, Buck B, Rempel J, Sahlas D, Kelly ME, Budzik R, Tymianski M, Hill MD, Goyal M; ESCAPE-NA1 Investigators. Prevalence of "Ghost Infarct Core" after Endovascular Thrombectomy. AJNR Am J Neuroradiol. 2024 Mar 7;45(3):291-295. doi: 10.3174/ajnr.A8113.

  PMID: 38272571 DERIVED

• Fladt J, Guo J, Specht JL, Wang M, Chan LL, Mctaggart R, Buck BH, Aviv R, Swartz RH, Field TS, Tarpley J, Shah R, Goyal M, Tymianski M, Hill MD, Demchuk A, d'Esterre C, Barber P. Infarct Evolution on MR-DWI After Thrombectomy in Acute Stroke Patients Randomized to Nerinetide or Placebo: The REPERFUSE-NA1 Study. Neurology. 2024 Jan 23;102(2):e207976. doi: 10.1212/WNL.0000000000207976. Epub 2023 Dec 22.

  PMID: 38165335 DERIVED

• Singh N, Cimflova P, Ospel JM, Kashani N, Marko M, Mayank A, Hill MD; ESCAPE-NA1 Trial Investigators. Prevalence and Predictors of Multivessel Occlusions at Baseline Imaging in ESCAPE-NA1 Trial. Stroke. 2023 Jun;54(6):e233-e234. doi: 10.1161/STROKEAHA.123.043027. Epub 2023 May 11. No abstract available.

  PMID: 37165867 DERIVED

• Singh N, Cimflova P, Ospel JM, Kashani N, Marko M, Mayank A, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Rempel JL, Field TS, Dowlatshahi D, van Adel B, Swartz RH, Shah R, Sauvageau E, Puetz V, Silver FL, Campbell B, Chapot R, Tymianski M, Goyal M, Almekhlafi MA, Hill MD; ESCAPE-NA1 Trial Investigators. Infarcts in a New Territory: Insights From the ESCAPE-NA1 Trial. Stroke. 2023 Jun;54(6):1477-1483. doi: 10.1161/STROKEAHA.122.042200. Epub 2023 Apr 21.

  PMID: 37082967 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic 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, MD PhD
• Organization: NoNO Inc.

mtymianski@nonoinc.ca

4165831687

Study Officials

• Michael D Hill, MD MSc

  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: October 6, 2016
• First Posted: October 11, 2016
• Study Start: March 1, 2017
• Primary Completion: November 20, 2019
• Study Completion: November 20, 2019
• Last Updated: October 10, 2022
• Results First Posted: December 14, 2020

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); US (20); CA (14); KR (4); IE (2); AU (2); GB (1); DE (5)