Delving into the Latest Updates on Nerinetide with Synapse

Overview

Basic Info

Drug Type

Recombinant polypeptide

Synonyms

Nerinetide (USAN/INN)

+ [2]

Target

PSD95

Mechanism

PSD95 inhibitors(Disks large homolog 4 inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular Diseases

Active Indication

Acute Ischemic StrokeBrain Ischemia

Inactive Indication

AneurysmAneurysm, RupturedBrain Injuries, Traumatic+ [2]

Originator Organization

NoNO, Inc.

Active Organization

NoNO, Inc.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 80946

Source: *****

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

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100 Translational Medicine associated with Nerinetide

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100 Patents (Medical) associated with Nerinetide

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84

Literatures (Medical) associated with Nerinetide

01 Jan 2025·Stroke

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial

Article

Author: Menon, Bijoy K. ; Campbell, Bruce ; Silver, Frank L. ; van Adel, Brian ; Chapot, René ; Almekhlafi, Mohammed A. ; Rempel, Jeremy L. ; Heard, Kathy ; Field, Thalia S. ; Nogueira, Raul G. ; Tymianski, Michael ; Swartz, Richard H. ; Demchuk, Andrew M. ; Joshi, Manish ; Dowlatshahi, Darius ; Goyal, Mayank ; Hill, Michael D. ; Shah, Ruchir ; Kashani, Nima ; Puetz, Volker ; Sauvageau, Eric ; Ospel, Johanna M. ; Poppe, Alexandre Y. ; Zerna, Charlotte ; McTaggart, Ryan A.

BACKGROUND:In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide’s effect on infarct volume.METHODS:ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo. Patients not receiving intravenous alteplase were included in this post hoc secondary analysis of the trial data. Final infarct volume was manually segmented on 24-hour noncontrast computed tomography or diffusion-weighted magnetic resonance imaging. Predictors of final infarct volume were identified using multivariable linear regression with cubic-root-transformed infarct volume as the dependent variable. Evidence of treatment-by-predictor interaction was tested by including interaction terms in the model.RESULTS: Four hundred forty-six patients (219 who received nerinetide and 227 who received a placebo) out of a total of 1105 enrolled patients were included in this secondary post hoc analysis of the randomized ESCAPE-NA1 trial. Nerinetide was a strong predictor of smaller infarct volume (adjusted β coefficient, −0.35 [95% CI, −0.67 to −0.02]). Other predictors of smaller infarct volume were history of hypertension, good pial collateral filling on multiphase computed tomography angiography, a middle cerebral artery occlusion compared with an internal carotid artery occlusion, lower baseline National Institutes of Health Stroke Scale score, lower baseline systolic blood pressure, lower baseline serum glucose, shorter onset-to-randomization time, and higher Alberta Stroke Program Early CT Score. There was evidence of a treatment-by-systolic blood pressure and treatment-by-anesthesia interaction: nerinetide attenuated the negative effects of elevated baseline ( Pinteraction =0.02) and postdose ( Pinteraction =0.04) systolic blood pressure and use of general anesthesia ( Pinteraction =0.06) on final infarct volume. We observed a marginally significant interaction with reperfusion status, such that nerinetide may attenuate the harmful effect of poor reperfusion status on infarct volume ( Pinteraction =0.08). CONCLUSIONS:Nerinetide treatment was strongly associated with smaller final infarct volumes among patients not cotreated with alteplase. The reduction in infarct volume was greater among patients with poor prognostic factors.REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02930018.

01 Dec 2024·Journal of the Neurological Sciences

Prevalence of ipsilateral “vulnerable carotid plaques with <50 % stenosis” on CT angiography in embolic stroke of undetermined source

Article

Author: Singh, Nishita ; Almekhlafi, Mohammed A ; Hill, Michael D ; Buck, Brian ; Poppe, Alexandre Y. ; Ospel, Johanna M ; Poppe, Alexandre Y ; Bosshart, Salome ; Uchida, Kazutaka ; Ospel, Johanna M. ; Demchuk, Andrew M. ; Demchuk, Andrew M ; Hill, Michael D. ; Stebner, Alexander ; Ganesh, Aravind ; Goyal, Mayank ; Marko, Martha ; Almekhlafi, Mohammed A.

BACKGROUNDCarotid plaques may be an important etiology in ischemic stroke. We aimed to assess carotid plaque characteristics ipsilateral and contralateral to the ischemic stroke and assessed the prevalence of "vulnerable carotid plaques with <50% stenosis" based on different imaging-based definitions in patients with large vessel occlusion and source of embolic stroke of undetermined source (ESUS) on CT Angiography (CTA).METHODSData are from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke), a multicenter, randomized study that included anterior circulation large vessel occlusion patients undergoing thrombectomy. Various CTA features of plaque vulnerability were combined to define "vulnerable carotid plaques" in different ways. Within ESUS patients, prevalence of vulnerable plaques ipsilateral vs. contralateral to the intracranial occlusion was compared.RESULTSWe analyzed 132 patients whose ischemic stroke mechanism was determined to be ESUS. Plaques causing 30-50 % stenosis (as compared to no stenosis) and plaque surface irregularity were significantly more common in ipsilateral carotid arteries (37[28.0 %] vs. 18[13.6 %]; p < 0.001 and 102[77.3 %] vs. 78[59.1 %]; p = 0.002). The prevalence of ipsilateral "vulnerable carotid plaques" varied depending on imaging definition used for such plaques between 55 and 74 %, but irrespective of the definition used, the prevalence of "vulnerable carotid plaques" was consistently higher in ipsilateral carotid arteries compared to contralateral carotid arteries.CONCLUSIONSIn ESUS patients undergoing thrombectomy for anterior circulation large vessel occlusion, vulnerable carotid plaques are more prevalent ipsilateral to the intracranial occlusion. Irregular plaque surface, and a higher degree of stenosis were the most common vulnerable plaque features.

01 Aug 2024·Stroke

HERMES-24 Score Derivation and Validation for Simple and Robust Outcome Prediction After Large Vessel Occlusion Treatment

Article

Author: Guillemin, Francis ; Brown, Scott ; Demchuk, Andrew M. ; Najm, Mohamed ; Roos, Yvo B.W.E.M. ; Mitchell, Peter J. ; Jovin, Tudor G. ; White, Phil M. ; Bracard, Serge ; Campbell, Bruce C.V. ; van Zwam, Wim H. ; Muir, Keith W. ; Goyal, Mayank ; Dowlatshahi, Dar ; Saver, Jeffrey L. ; Hill, Michael D. ; Tanaka, Koji ; Menon, Bijoy K.

BACKGROUND:Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy.METHODS:Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441). From a set of candidate predictors, logistic regression modeling using forward variable selection was used to select a model that was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in validation cohort, control arm (n=893), and external validation cohorts from the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke; n=1066) and INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography; n=614).RESULTS:In the derivation cohort, we selected 2 significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale score at 24 hours and age [β-coefficient, 0.34 and 0.06]) and derived the HERMES-24 score: age (years)/10+National Institutes of Health Stroke Scale score at 24 hours. The HERMES-24 score was highly predictive for mRS ≤2 (c-statistic 0.907 [95% CI, 0.879–0.935]) in the derivation cohort. In the validation cohort and the control arm, the HERMES-24 score predicts mRS ≤2 (c-statistic, 0.914 [95% CI, 0.886–0.944] and 0.909 [95% CI, 0.887–0.930]). Observed provability of mRS ≤2 ranged between 3.1% and 3.4% when HERMES-24 score ≥25, while it ranged between 90.6% and 93.0% when HERMES-24 score <10 in the derivation cohort, validation cohort, and control arm. The HERMES-24 score also showed c-statistics of 0.894 and 0.889 for mRS ≤2 in the ESCAPE-NA1 and INTERRSeCT populations.CONCLUSIONS:The post-treatment HERMES-24 score is a simple validated score that predicts a 3-month outcome after anterior circulation large vessel occlusion stroke regardless of intervention, which helps prognostic discussion with families on day 2.

100 Deals associated with Nerinetide

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External Link

KEGG	Wiki	ATC	Drug Bank
D11729	-	-	DB12595

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Ischemic Stroke	Phase 3	DE	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	US	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	CA	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 3	AU	NoNO, Inc.	01 Mar 2017
Brain Ischemia	Phase 3	CA	NoNO, Inc.	26 Mar 2015
Acute Ischemic Stroke	Phase 2	KR	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Phase 2	IE	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Discovery	GB	NoNO, Inc.	01 Mar 2017
Acute Ischemic Stroke	Discovery	SE	NoNO, Inc.	01 Mar 2017
Aneurysm	Discovery	US	NoNO, Inc.	01 Aug 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02930018 (REPERFUSE-NA1, ISC2022)	Phase 3	Infarction	71	NA1	xobzpyeqpe(emqnhxvlig) = spitzfoibr hznxumtktt (clmbduftbh, 5.9 - 28.1) View more	-	01 Feb 2022
				Placebo	xobzpyeqpe(emqnhxvlig) = uvmgzikmgh hznxumtktt (clmbduftbh, 3.1 - 27.0) View more
ESCAPE NA1-Trial (ISC2021)	Not Applicable	Stroke \| occlusions	1,105	Nerinetide	xlsryfchpm(jcknicgupw) = plcyjoqmpf tuqhzvfape (kvbroukevz )	-	01 Mar 2021
				Placebo	xlsryfchpm(jcknicgupw) = bphzukudio tuqhzvfape (kvbroukevz )
NCT02930018 (ESCAPE-NA1 \| REPERFUSE-NA1, CTgov)	Phase 3	Acute Ischemic Stroke	1,105	Placebo	htzoanrufz(bhxnlnqsce) = spnjlryxbj sateoiirrr (ofmqnuhkvi, ospdhqwqcu - tnuvhnntln) View more	-	14 Dec 2020
NCT02930018 (ESCAPE-NA1, Pubmed \| Lancet) Manual	Phase 3	Acute Ischemic Stroke	1,105	nerinetide	(zgzqcgxwdt) = Serious adverse events occurred equally between groups. fmxkbbdwwi (likwemebsy ) View more	Negative	14 Mar 2020
				Placebo
NCT00728182 (ENACT, CTgov)	Phase 2	Stroke \| Aneurysm	185	NA-1 (1 NA-1)	lrjfkmibwq(mcezkrgxmp) = vltewpifft bhyqowdnyc (agnfpzfqyg, enxgbgnrcy - nqjeplaawt) View more	-	17 Oct 2013
				placebo (2 Placebo)	lrjfkmibwq(mcezkrgxmp) = jhlfzhfzwg bhyqowdnyc (agnfpzfqyg, uhqtfraiix - nvpyghtxwy) View more