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

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).

Start Date06 Dec 2020

Sponsor / Collaborator

NoNO, Inc.

[+1]

NCT02930018

/ CompletedPhase 3

A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Intravenous NA-1 in Subjects With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy

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.

Start Date01 Mar 2017

Sponsor / Collaborator

NoNO, Inc.

[+1]

NCT02056574

/ WithdrawnPhase 2

Phase 2, Multicenter Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study Evaluating a Single Dose of Intravenous NA-1 in Patients With Subarachnoid Hemorrhage Undergoing Endovascular Repair of Ruptured Intracranial Aneurysms

This is a randomized, double-blind, placebo-controlled, single-dose study investigating the safety and efficacy of NA-1 in patients with subarachnoid hemorrhage (SAH) undergoing endovascular repair of ruptured intracranial aneurysms. Up to 300 male and female patients with SAH undergoing endovascular repair of a ruptured intracranial aneurysm will be dosed with 2.60 mg/kg of NA-1 or placebo as a 10 minute intravenous infusion after completion of the endovascular procedure on Day 1 of the study period. Subjects will undergo interim procedures at Day 2-4, Day 30-45, and end-of-study procedures on Day 90.

Start Date01 Nov 2015

Sponsor / Collaborator

NoNO, Inc.

100 Clinical Results associated with Nerinetide

100 Translational Medicine associated with Nerinetide

100 Patents (Medical) associated with Nerinetide

Literatures (Medical) associated with Nerinetide

01 Sep 2026·Journal of the American Heart Association

Correction to: Safety and Efficacy of Nerinetide at Year in Participants Enrolled in ESCAPE‐NEXT: A Multicenter, Double‐Blind, Randomized Controlled Trial

Article

01 Sep 2026·Drug Delivery and Translational Research

The PSD-95 inhibitor NA-1 is delivered to the brain upon nasal administration with uptake into the olfactory bulb improved by co-administration with the cell-penetrating peptides lowPro and Tat

Article

Author: Bente Gammelgaard ; Gunhild Joensen ; Mie Kristensen ; Maria Thaysen ; Katharina Schindowski ; Solveig Elle Schmidt ; Camilla Sandbjerg

Abstract:

Ischemic stroke affects millions of people annually with limited treatment options targeting excitotoxicity, a major cause of cognitive impairment. The PSD-95 inhibitor NA-1 has demonstrated neuroprotective potential, but its efficacy via intravenous administration is hindered by broad systemic distribution, reduced brain exposure, and interaction with thrombolytic agents like alteplase. This study explores the potential of nasal administration as an alternative delivery route to enhance brain uptake and reduce systemic off-target effects of NA-1. A porcine primary olfactory model was exploited to evaluate NA-1 permeability and the impact of co-administration with the cell-penetrating peptides Tat, LowPro, and PenShuf. NA-1 alone permeated the model to a greater extent than a similar sized model dextran compound, with PenShuf improving NA-1 permeability but compromising barrier integrity in vitro. In vivo, nasal administration to mice achieved brain uptake of NA-1, particularly in the olfactory bulb, with co-administration of Tat and LowPro enhancing olfactory bulb delivery. Compared to intravenously administered NA-1, nasal delivery resulted in significantly lower off-target tissue distribution. These findings highlight nasal administration as a qualified alternative for NA-1 delivery, with potential to bypass the limitations of intravenous administration and enable concurrent use with alteplase during acute ischemic stroke.

01 Aug 2026·Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences

Health economic impact of Nerinetide in addition to mechanical thrombectomy without concurrent alteplase

Article

Author: Mayank Goyal ; Michael Hill ; Michael Tymianski ; Corey Adams ; Johanna M Ospel

Background and purpose:

The ESCAPE-NA1 trial has shown that intravenous Nerinetide improves clinical outcomes in acute ischemic stroke patients with large vessel occlusion undergoing endovascular treatment without concurrent intravenous alteplase. We assessed the health economic impact of intravenous Nerinetide as an adjunctive treatment in endovascular treatment patients who do not receive concurrent intravenous alteplase.

Methods:

Data are from the ESCAPE-NA1 trial, in which acute ischemic stroke with large vessel occlusion endovascular treatment patients were randomized to receive intravenous Nerinetide or placebo. Only those patients not treated with concurrent intravenous alteplase were included in this analysis. We used a Markov state transition model (12 months cycle length) to estimate expected lifetime costs and outcomes, assuming Nerinetide cost being zero for the purpose of this analysis. We calculated incremental cost-effectiveness ratios and derived mean net monetary benefits with 95% prediction intervals from a probabilistic sensitivity analysis. Upper, middle, and lower willingness-to-pay thresholds were set at $50,000,$100,000, and $150,000.

Results:

The incremental cost-effectiveness ratio for Nerinetide in addition to endovascular treatment was $13,721/quality-adjusted life year (healthcare perspective) and $14,453/quality-adjusted life year (societal perspective). At the upper willingness-to-pay threshold, Nerinetide in addition to endovascular treatment resulted in a higher mean net monetary benefit compared to endovascular treatment alone, both from a healthcare perspective (449,526 [95% prediction interval: 448,627–450,425] vs. 382,584 [381,781–383,386]) and a societal perspective (350,750 [349,842–351,658] vs. 282,896 [282,068–283,725]). Mean net monetary benefits were also higher for Nerinetide in addition to endovascular treatment at the middle and lower willingness-to-pay thresholds.

Conclusion:

Treating patients with a cerebroprotectant, such as Nerinetide, in addition to endovascular treatmentl in patients who cannot receive intravenous alteplase may be beneficial from a health-economic standpoint.

News (Medical) associated with Nerinetide

22 Nov 2022

·www.nonoinc.ca

NoNO Inc. Announces First Patient Dosed with NoNO-42 in a First in Humans Phase 1 Study

TORONTO, Nov 22, 2022 – NoNO Inc. is pleased to announce the dosing of the first participant in its Phase 1 clinical trial evaluating NoNO-42. NoNO-42 is the next generation drug developed in NoNO’s PSD-95 inhibitor platform. It is intended for the treatment of all people experiencing an acute ischemic stroke. The first in human study with NoNO-42 will evaluate the safety, tolerability and pharmacokinetics of single ascending doses of NoNO-42 in consecutive cohorts of healthy volunteers. NoNO-42 builds on NoNO’s ground-breaking results for its first-generation PSD-95 inhibitor, nerinetide. In the Phase 3 ESCAPE-NA1 trial, participants who were treated with nerinetide but not with thrombolytics (“clot-busters”) exhibited improved functional independence, reduced stroke mortality, and reduced brain damage on medical imaging. ESCAPE-NA1 was conducted in stroke in patients who were selected to undergo endovascular thrombectomy, a treatment in which the blood clots causing the stroke are removed in order to restore blood flow to the brain. The study provided evidence that such patients may benefit from nerinetide if they are not previously treated with thrombolytics. However, in patients who had already received thrombolytic treatment nullified the efficacy of nerinetide. The results in the no-thrombolytic arm are currently under confirmatory testing in the ongoing Phase 3 ESCAPE-NEXT trial. NoNO-42 was developed to be administered with or without thrombolytic agents. It extends the potential benefits of PSD-95 inhibition to those patients who, in ESCAPE-NA1 were previously treated with thrombolytics and therefore could not benefit from nerinetide. “The Phase 1 trial of NoNO-42 is a key milestone in extending the benefits of PSD-95 inhibition all acute ischemic stroke patients. Given NoNO-42’s similarities to nerinetide in all material clinical aspects other than its expected efficacy with or without thrombolytics, success with current pivotal trials with nerinetide will de-risk NoNO-42 development substantially” said Dr. Michael Tymianski, President, CEO and founder of NoNO Inc. “The stroke neurology community is extremely excited about the prospects of both nerinetide and NoNO-42, and the academic community is eager to follow-up ESCAPE-NEXT with clinical trials to investigate the efficacy of NoNO-42 in stroke patients” said Dr. Michael Hill, MD, Global Principal Investigator and Professor of Neurology at the Cumming School of Medicine, University of Calgary. NoNO Inc. is a clinical stage, stroke-focused Ontario biotechnology company dedicated to offering people who experience stroke opportunities for a better life. NoNO’s therapeutic strategy is to inhibit key protein-protein interactions of PSD-95 that are involved selectively in cellular signals that cause stroke damage, but without interfering with normal cell functions. Our PSD-95 inhibitor platform consists of: Nerinetide, NoNO’s lead compound for people experiencing an ischemic stroke, currently completing its second global Phase 3 trail in people not previously treated with a clot dissolving drug. NoNO-42, in Phase 1 for use alongside clot dissolving drugs for all people experiencing ischemic stroke. NoNO-SC, administered subcutaneously to enable the treatment of people experiencing stroke outside of medical setting by anyone – anywhere. For more information, please visit www.nonoinc.ca.

Phase 1Phase 3Phase 2

22 Mar 2022

·www.nonoinc.ca

NoNO Inc. Announces the Start of the Global Phase 3 ESCAPE-NEXT Trial of the Peptide Nerinetide in Acute Ischemic Stroke Excluding Thrombolysis

TORONTO, Dec 6, 2020 – NoNO Inc. is pleased to announce the enrollment of the first patient in the ESCAPE-NEXT trial, NoNO’s second global phase 3 trial of its lead peptide, Nerinetide. ESCAPE-NEXT is 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 (EVT). ESCAPE-NEXT is informed by the ESCAPE-NA1 trial which suggested that treatment with nerinetide may improve functional independence, reduce stroke mortality, and reduce brain damage due to stroke in patients who undergo EVT without the prior administration of thrombolytic (“clot busting”) agents. ESCAPE-NA1 results were presented at the 2020 International Stroke Conference in February. “Our prior trial showed us which stroke patients may benefit from nerinetide. ESCAPE-NEXT is a further pivotal study, focused on those patients, and is intended to confirm the promising findings of clinical benefits suggested by ESCAPE-NA1. ESCAPE-NEXT has a substantially similar design, but focuses on those patients who may experience the greatest benefit from nerinetide” said Dr. Michael Tymianski, President, CEO and founder of NoNO Inc. “We are exploring a novel mechanism of action for a new drug in a very common, but devasting disease. A new drug for acute ischemic stroke has the potential to further transform stroke therapeutics,” said Dr. Michael Hill, MD, Global Principal Investigator and Professor of Neurology at the Cumming School of Medicine, University of Calgary. ESCAPE-NEXT is designed to evaluate the clinical benefits of nerinetide in acute stroke patients who are selected for endovascular revascularization without prior treatment with intravenous thrombolytic therapy. The trial will enroll adult participants in the USA, Canada, Europe and Australia. It has an initial enrollment target of 680 participants, with an option to increase the sample to 1020 following an interim analysis. Pivotal outcomes will be evaluated at 90 days with a further analysis at one year after the stroke.

Phase 3

22 Mar 2022

·www.nonoinc.ca

Press Release - NoNO Inc. | Change Everything

Toronto, Canada, April 7, 2021, 2PM ET – NoNO Inc., an Ontario biotechnology company developing innovative neurotherapeutics for acute stroke and other central nervous system disorders, announced today the publication of prototypes for next generation protease-resistant PSD-95 inhibitors. Published in the journal Science Translational Medicine, the article entitled “Plasmin-resistant PSD-95 inhibitors resolve effect-modifying drug-drug interactions between alteplase and nerinetide in acute stroke” demonstrates the potential of novel next-generation protease-resistant compounds for the treatment of acute ischemic strokes. Such compounds may be practically integrated into current stroke care workflows without the need to modify existing medical practice. These next generation compounds are expected to extend the therapeutic utility of PSD-95 inhibition to all eligible stroke patients, including those that are treated with drugs such as alteplase. The next generation compounds build on nerinetide, NoNO Inc.’s clinical stage lead PSD-95 inhibitor compound. Nerinetide was recently tested in the Phase 3 ESCAPE-NA1 study which provided promising results for the clinical safety and efficacy of nerinetide in acute ischemic stroke, as published in the journal The Lancet. ESCAPE-NA1 showed that nerinetide is promising in stroke patients who do not receive prior treatment with the thrombolytic agent, alteplase, and this is currently being evaluated further in the ongoing global Phase 3 ESCAPE-NEXT study. If ESCAPE-NEXT is successful, both studies will provide support for PSD-95 inhibition as a platform therapy for stroke and related neurological disorders. NoNO Inc. CEO Dr. Michael Tymianski commented that, “Nerinetide and next generation PSD-95 inhibitors continue to grow as a strategy for treating a wide range of neurological disorders that implicate excitotoxicity and neuroplasticity. Neuroprotection for acute ischemic stroke is achievable, and with continued improvements in our PSD-95 inhibitor technology, providing a benefit to patients in additional indications such as stroke recovery, traumatic brain injury and Alzheimer’s disease should be achievable as well.” NoNO Inc. is an Ontario biotechnology company whose focus is on developing therapeutic drugs in areas of unmet medical needs. Its drug pipeline includes therapeutic agents in various stages of development ranging from cellular and molecular discovery to human clinical trials. Its lead projects relate to diseases of the nervous system whose mechanisms involve the protein PSD-95, including stroke, traumatic brain injury and neuropathic pain. NoNO Inc.’s strategy is to inhibit key protein-protein interactions of PSD-95 that are involved selectively in cellular signals that cause cell damage, but without interfering with normal cell functions. For more information, please visit www.nonoinc.ca.

Phase 3Clinical Result

100 Deals associated with Nerinetide

External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 3	United States	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Australia	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Canada	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Germany	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Ireland	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	South Korea	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	Sweden	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	United Kingdom	NoNO, Inc.	01 Mar 2017
Brain Ischemia	Phase 3	Canada	NoNO, Inc.	26 Mar 2015
Intracranial Aneurysm	Phase 2	United States	NoNO, Inc.	01 Nov 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04462536 (ESCAPE-NEXT, CTgov)	Phase 3	Acute Ischemic Stroke	850	Placebo (Placebo)	maxsabvsog = akxqjfpfci kdkabsqwoe (fydvwgtqyn, xvhmiprflu - ygafeamoxm) View more	-	22 Jun 2025
				Nerinetide (Nerinetide)	maxsabvsog = cdbghbqoxo kdkabsqwoe (fydvwgtqyn, qkmuhhlete - venyulfrkb) View more
NCT02930018 (ESCAPE-NA1, Pubmed \| Neurology)	Phase 3	Stroke	-	Nerinetide	ysaoakygdj(ypmydpidnx) = gqgeodmshd jztqjcfmkp (shvwfjjfju, 1.09 - 21.30) View more	Negative	23 Jan 2024
				Placebo	ysaoakygdj(ypmydpidnx) = kuieeeghkr jztqjcfmkp (shvwfjjfju, 2.54 - 21.81) View more
NCT00728182 (ENACT, AAN2022)	Phase 2	Brain Infarction	184	Nerinetide treatment	xchdsgyyex(snvcexuvmz): P-Value = 0.020 View more	Positive	03 May 2022
				Placebo
NCT02930018 (REPERFUSE-NA1, ISC2022)	Phase 3	Infarction	71	NA1	iakmuhvoap(tupyyfadca) = ftpuyapgig rzdruwvosr (djvzlikebh, 5.9 - 28.1) View more	-	01 Feb 2022
				Placebo	iakmuhvoap(tupyyfadca) = okwxxgzysu rzdruwvosr (djvzlikebh, 3.1 - 27.0) View more
NCT02930018 (ESCAPE-NA1 \| REPERFUSE-NA1, CTgov)	Phase 3	Acute Ischemic Stroke	1,105	Placebo	ckjcxpxxxw = wczoujzjzt crjdpmlzkl (diugghndiv, vsrafayepc - inefvsucbw) View more	-	14 Dec 2020
NCT02930018 (ESCAPE-NA1, Pubmed \| Lancet) Manual	Phase 3	Acute Ischemic Stroke	1,105	nerinetide	mabvmleiyx(ehablbntgr) = Serious adverse events occurred equally between groups. lerigpglyq (ptofqrhqds ) View more	Negative	14 Mar 2020
				Placebo
NCT00728182 (ENACT, CTgov)	Phase 2	Stroke \| Aneurysm \| Ischemic stroke ... View more	185	NA-1 (1 NA-1)	ypnrlowqbl(qrsuthnpjj) = gflagfidgo svyiykulfy (gdruekvoqz, 5598) View more	-	17 Oct 2013
				placebo (2 Placebo)	ypnrlowqbl(qrsuthnpjj) = oqqicgbege svyiykulfy (gdruekvoqz, 1611) View more

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