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

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.

Timeline

Start

2017-03-01

Primary completion

2019-11-20

Completion

2019-11-20

Outcome

Missed primary endpoint

registry analysis (superiority test); Placebo vs Nerinetide, 2.6 mg/kg; p = 0.335; Odds Ratio (OR) 1.146 (95% CI 0.869 to 1.511); NCT02930018 ↗

paper Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. PMID 32087818 ↗

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Results 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.
• 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. 2026 Feb 16;18(3):667-674. doi: 10.1136/jnis-2025-023103.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Nerinetide	Peptide	2.6 mg/kg	Intravenous

Indications