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

27 May 2025·NEUROLOGY

Impact of Brain Frailty on Clinical Presentation and Neurologic Recovery in Acute Ischemic Stroke Patients Undergoing Thrombectomy

Article

BACKGROUND AND OBJECTIVES:

Brain frailty impairs the ability to compensate for brain dysfunction and is linked to worse outcomes after stroke. Stroke severity at presentation is a key determinant of outcomes in acute ischemic stroke. This study aimed to examine the impact of brain frailty on initial stroke severity and recovery in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT).

METHODS:

We conducted a post hoc analysis of the ESCAPE-NA1 randomized-controlled trial that investigated the efficacy and safety of the neuroprotectant nerinetide in patients with AIS who received EVT. Brain frailty markers (cortical atrophy, subcortical atrophy, white matter hyperintensities, chronic infarcts) were visually assessed from baseline noncontrast CT scans. We explored the association between these markers and admission stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) using multivariable quantile regression. We also assessed the NIHSS trajectory over 90 days using repeated-measures analysis. Models were adjusted for relevant covariates.

RESULTS:

Among 1,102 participants (mean age 69.5 years; 49.7% female), NIHSS scores at baseline were higher in patients with cortical atrophy and those with chronic infarcts compared with patients having no cortical atrophy or chronic infarcts after adjusting for confounders (adjusted difference for GCA1 vs GCA0 = 1.25 points [95% CI 0.18-2.31], p = 0.021; adjusted difference for presence of chronic infarcts = 1.27 points [95% CI 0.007-2.53, p = 0.049]). Subcortical atrophy, white matter hyperintensity burden, lacunes, and overall brain frailty were not associated with NIHSS scores at presentation. A repeated-measures analysis showed consistent higher NIHSS scores in individuals with brain frailty compared with those without, after the acute phase throughout the 90-day follow-up period (NIHSS score at 30 days, adjusted difference for total brain frailty score 1 vs 0 = 1.16 points [95% CI 0.35-1.96], p = 0.01; brain frailty score 2/3 vs 0 = 0.98 [95% CI 0.08-1.88], p = 0.03; NIHSS score at 90 days (adjusted difference for brain frailty score 1 vs 0 = 0.97 [95% CI 0.19-1.75], p = 0.01; brain frailty score 2/3 vs 0 = 0.85 [95% CI -0.01 to -1.71], p = 0.05).

DISCUSSION:

This study highlights the association of brain frailty with the clinical presentation and recovery trajectory of patients with AIS undergoing EVT. Specifically, cortical atrophy was independently associated with baseline stroke severity, and the total burden of brain frailty was independently associated with NIHSS recovery trajectories. The results emphasize the importance of considering brain frailty in acute stroke management and prognostication.

01 Mar 2025·LANCET NEUROLOGY

Safety and efficacy of nerinetide in patients with acute ischaemic stroke enrolled in the early window: a post-hoc meta-analysis of individual patient data from three randomised trials

Article

BACKGROUND:

In three neuroprotection trials of nerinetide for acute ischaemic stroke, inconclusive results have been reported with respect to the prespecified primary outcome. However, none of the trials faithfully replicated the inclusion criteria of the animal studies that provided the rationale for the clinical trials-ie, treatment within 3 h of stroke onset and selected for reperfusion without previous thrombolysis. We aimed to investigate whether a clinical benefit of nerinetide might be seen in the subgroup of patients enrolled in these three clinical trials who met the criteria used in the animal studies.

METHODS:

In this post-hoc individual patient data meta-analysis, we pooled data from the ESCAPE-NA1, ESCAPE-NEXT, and FRONTIER trials, which were done at 135 stroke centres in 13 countries (Canada, Australia, Germany, Ireland, Italy, the Netherlands, Norway, Singapore, South Korea, Sweden, Switzerland, the UK, and the USA). We included all participants who were enrolled within 3 h of acute ischaemic stroke onset, treated with study drug (nerinetide or placebo; randomised 1:1), and selected for reperfusion with thrombolysis, endovascular thrombectomy, or both. The primary endpoint was the number of responders at day 90, which was defined as people with a favourable outcome as per the primary endpoint prespecified in their respective trial. The primary endpoint was analysed by logistic regression, adjusted for age, stroke severity, and trial.

FINDINGS:

Between March 26, 2015, and Jan 31, 2023, 2487 participants were enrolled in the three trials, of whom 690 met criteria for this pooled analysis (389 participants in the nerinetide group and 301 participants in the placebo group). 364 (53%) of 690 participants were men and 326 (47%) were women. The median age of participants was 76 years (IQR 66-83) and median baseline National Institutes of Health Stroke Scale score was 17 (11-21). 216 (56%) of 389 participants were responders at day 90 in the nerinetide group compared with 144 (48%) of 301 in the placebo group (adjusted odds ratio [aOR] 1·48, 95% CI 1·07-2·06; p=0·017). 62 (16%) of 389 people in the nerinetide group died compared with 55 (18%) of 301 people in the placebo group (aOR 0·81, 95% CI 0·53-1·24; p=0·34). No safety concerns were identified in either group.

INTERPRETATION:

Nerinetide showed a clinically significant benefit over several outcome measures, including the modified Rankin Scale score, the incidence of stroke worsening, and infarction volumes. Neuroprotection with nerinetide might, therefore, be indicated for patients within 3 h of stroke onset and who are selected for reperfusion. These inclusion criteria should be tested in a future trial.

FUNDING:

None.

01 Mar 2025·STROKE

Comparison of Noncontrast Computed Tomography, Multiphase Computed Tomography Angiography, and Computed Tomography Perfusion to Assess Infarct Growth Rate in Acute Stroke

Article

Author: Stebner, Alexander ; Field, Thalia S. ; Pensato, Umberto ; Hill, Michael D. ; Bang, Oh Young ; Ospel, Johanna M. ; Goyal, Mayank ; Puetz, Volker ; Bosshart, Salome L. ; Demchuk, Andrew M. ; Sahlas, Demetrios J. ; Buck, Brian H. ; Dowlatshahi, Dar

BACKGROUND::

Infarct growth rate is remarkably heterogeneous in acute ischemic stroke, reflecting diverse clinical-physiological phenotypes. We compared different methods of estimating infarct growth rate in patients with acute ischemic stroke undergoing thrombectomy using multimodal computed tomography (CT) stroke imaging.

METHODS::

Secondary analysis of the international ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) which evaluated the effect of nerinetide in patients with large vessel occlusion undergoing thrombectomy. Infarct growth rate was estimated leveraging each component of multimodal stroke CT imaging: (1) 10 minus baseline Alberta Stroke Program Early CT Score (ASPECTS) divided by hours elapsed from symptom onset on noncontrast CT (ASPECTS decay per hour); (2) collateral status on multiphase CT angiography (mCTA), and (3) hypoperfusion intensity ratio on CT perfusion. Patients were dichotomized into intermediate and slow progressors (since fast progressors were likely to be excluded from ESCAPE-NA1 based on trial enrollment criteria) according to median ASPECTS decay, presence of good versus moderate/poor mCTA collaterals, and median hypoperfusion intensity ratio, respectively. Associations between progressor phenotypes and 90-day modified Rankin Scale score were assessed across neuroimaging modalities using adjusted logistic regression analyses.

RESULTS::

Among 1105 patients enrolled in ESCAPE-NA1 between 2017 and 2019, 619 (56.0%) were assessed for progressor phenotypes using noncontrast CT, 1084 (98.1%) with mCTA, and 415 (37.6%) with CT perfusion. Median ASPECTS decay per hour was 1.05 (interquartile range, 0.05–1.85), 188/1084 (17%) patients had good collateral status on mCTA, and the median hypoperfusion intensity ratio was 0.44 (interquartile range, 0.28–0.59). Intermediate progressors showed worse functional outcomes compared with slow progressors only in CT perfusion strata: adjusted common odds ratio for modified Rankin Scale ordinal shift analysis of 1.69 (95% CI, 1.14–2.49). No significant association between progressor phenotypes and 90-day modified Rankin Scale was seen when the noncontrast CT and the mCTA approaches were used.

CONCLUSIONS::

Stroke progressor phenotypes based on CT perfusion criteria (using the hypoperfusion intensity ratio approach) were associated with clinical outcomes, while stroke progressor phenotypes based on noncontrast CT (ASPECTS decay) and mCTA (collateral status) criteria were not.

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

KEGG	Wiki	ATC	Drug Bank
D11729	-	-	DB12595

R&D Status

10 top R&D records.

to view more data

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	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
Aneurysm, Ruptured	Phase 2	United States	NoNO, Inc.	01 Nov 2015
Aneurysm, Ruptured	Phase 2	Canada	NoNO, Inc.	01 Nov 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02930018 (REPERFUSE-NA1, ISC2022)	Phase 3	Infarction	71	NA1	thdqyrdkkz(mlsbeqqcxw) = iikgxyaojb dwilkzwhmy (alqygqjjvi, 5.9 - 28.1) View more	-	01 Feb 2022
				Placebo	thdqyrdkkz(mlsbeqqcxw) = lbwreooscf dwilkzwhmy (alqygqjjvi, 3.1 - 27.0) View more
NCT02930018 (ESCAPE-NA1 \| REPERFUSE-NA1, CTgov)	Phase 3	Acute Ischemic Stroke	1,105	Placebo	nwrysgdwrh = lazrcslnvw neiidgvknz (jpfqaurauh, ckwqdwpaet - jhulhdgivx) View more	-	14 Dec 2020
NCT02930018 (ESCAPE-NA1, Pubmed \| Lancet) Manual	Phase 3	Acute Ischemic Stroke	1,105	nerinetide	quxczjsydc(ltpargzmmw) = Serious adverse events occurred equally between groups. emipbbrtho (lkgyxpdgll ) View more	Negative	14 Mar 2020
				Placebo
NCT00728182 (ENACT, CTgov)	Phase 2	Stroke \| Aneurysm	185	NA-1 (1 NA-1)	coudsmcsqw(liqnfaxgej) = xiksrtltkt xudcbobiot (wlogitigtg, 5598) View more	-	17 Oct 2013
				placebo (2 Placebo)	coudsmcsqw(liqnfaxgej) = dzdwoitczo xudcbobiot (wlogitigtg, 1611) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis