Stroke, AcutePhase 3ESCAPE-NA1NCT02930018
Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke
A Phase 3 study testing Nerinetide (NA-1), 2.6 mg/kg in people with Stroke, Acute, run by NoNO Inc. at 50 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Acute
- What is being tested?
- Nerinetide (NA-1), 2.6 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,105 participants
- Where
- 50 sitesin 8 countries
- Study dates
- 1 Mar 2017to 20 Nov 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Signed informed consent from subject or legally authorized representative or, if required to enable inclusion by applicable national laws and regulations and the applicable independent review boards/Ethics Committee requirements for obtaining consent, from the investigator after consultation with an independent physician who is not otherwise participating in the trial.
Who cannot join
- 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.
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- 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).
- Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding study inclusion.
Trial locations and contacts
50 sites in 8 countries.
50 sites in 8 countries
United States20 sites
Grady Memorial Hospital
Atlanta, Georgia, 30303
NYU Lutheran Medical Center
Brooklyn, New York, 11220
Chattanooga Center for Neurologic Research
Chattanooga, Tennessee, 37403
Rush University Medical Center
Chicago, Illinois, 60612
Riverside Radiology
Columbus, Ohio, 43214
Swedish Medical Center
Englewood, Colorado, 80110
Valley Baptist Medical Center
Harlingen, Texas, 78550
Baptist Health Medical Center
Jacksonville, Florida, 32207
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
WellStar Health Systems
Marietta, Georgia, 30060
Yale New Haven Hospital
New Haven, Connecticut, 06510
Abington Memorial Hospital
Philadelphia, Pennsylvania, 19001
UPMC Presbyterian
Pittsburgh, Pennsylvania, 15213
Rhode Island Hospital
Providence, Rhode Island, 02903
California Pacific Medical Center - Davies Campus
San Francisco, California, 94114
Swedish Medical Center- Cherry Hill Campus
Seattle, Washington, 98122
Providence Little Company of Mary Medical Center Torrance
Torrance, California, 90503
Novant Health Forsyth Medical Center
Winston-Salem, North Carolina, 27103
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
Canada14 sites
University of Calgary - Foothills Medical Centre
Calgary, Alberta, T2N2T9
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
Queen Elizabeth II Health Science Centre
Halifax, Nova Scotia, B3H 3A7
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
London Health Sciences Centre- University Hospital
London, Ontario, N6A 5A5
CHUM Hopital Notre-Dame
Montreal, Quebec, H2L 4M1
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A1A1
The Ottawa Hospital
Ottawa, Ontario, K1Y 4E9
CHU de Quebec- Universite Laval- Hopital de l'Enfant-Jesus
Québec, Quebec, G1J 1Z4
Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8
Sunnybrook Health Centre
Toronto, Ontario, M4N 3M5
St Michael's Hospital
Toronto, Ontario, M5B 1W8
University Health Network - Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Vancouver Stroke Program Research Office/ Vancouver General Hosptial
Vancouver, British Columbia, V5Z 1M9
Germany5 sites
Universitätsklinikum Carl Gustav Carus Dresdner Neurovaskulares Centrum
Dresden, 01307
Klinik für Radiologie und Neuroradiologie
Essen, D - 45131
University Medical Center Goettingen
Göttingen, 37075
Universitätsklinikum Hamburg-Eppendorf
Hamburg
Neurologische Klinik, Universität Heidelberg
Heidelberg, 69120
South Korea4 sites
Dongsan Medical Centre
Daegu
Inha University Hospital
Incheon
Samsung Medical Center
Seoul
Yonsei Univ, Severence
Seoul
Australia2 sites
Royal Adelaide Hospital
Adelaide
Royal Melbourne Hospital
Parkville
Sweden2 sites
Skåne University Hospital
Lund
Karolinksa Institutet
Stockholm, 17176
About this study
Official title: 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.
Read the detailed description
Trial Objectives:
The primary objective is to determine the efficacy of the neuroprotectant, Nerinetide, in reducing global disability in subjects with major acute ischemic stroke (AIS) with a small established infarct core and with good collateral circulation selected for rapid endovascular revascularization.
The secondary objectives are to determine the efficacy of Nerinetide in:
- Reducing functional dependence
- Improving neurological outcome
- Improving activities of daily living
- Reducing mortality rate The leading safety objectives are to determine the effect of administering a dose of 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous (IV) infusion of Nerinetide to subject with acute stroke who are selected for endovascular revascularization on serious adverse events (SAEs) and 90-day mortality.
Trial Design:
This study is a Phase 3, randomized, multicentre, blinded, placebo-controlled, parallel group, single-dose design. Subjects harboring an acute ischemic stroke and who are selected for endovascular revascularization in accordance with local institutional practices and who harbor a small established infarct core and with good collateral circulation will be given a single, 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous dose of Nerinetide (NA-1) or placebo as soon as they are deemed to have met the enrollment criteria and with the intention of starting administration within 30 minutes of randomization. The randomization will be by stochastic minimization to balance baseline factors.
- Conditions
- Stroke, Acute
- Being tested
- Nerinetide (NA-1), 2.6 mg/kg, Placebo
- Keywords
- Acute Ischemic Stroke, Endovascular Thrombectomy, Neuroprotection, Tat-NR2B9c, NA-1, Nerinetide
- Medical subject headings
- Stroke, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nerinetide (NA-1), 2.6 mg/kgDrug
Also called NA-1
Single intravenous infusion of nerinetide over 10 ± 1 minutes
PlaceboDrug
Also called Drug vehicle only
Placebo Comparator: Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Drug vehicle only Receives: Drug: Placebo |
| Nerinetide (NA-1), 2.6 mg/kg | Experimental | Not described Receives: Drug: Nerinetide (NA-1), 2.6 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 Days
Secondary outcomes (2)
Number of Subjects With NIHSS Score of 0 to 2
Number of subjects with good neurological outcome, as defined by a score of 0 to 2 on the NIHSS at Day 90 or the last rating.
The National Institutes of Health Stroke Scale (NIHSS) is a standardized neurological examination score that is a valid and reliable measure of disability and recovery after acute stroke. Scores range from 0 to 42, with higher scores indicating increasing severity.
Measured: 90 Days or the last rating
Mortality Rate
Mortality rate, as defined by event rate (%) for mortality over the 90-day study period
Measured: 90 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2016 (estimated)
- Study start1 Mar 2017
- Primary completion20 Nov 2019
- Study completion20 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Stroke, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,105 participants (actual)
Sponsor and investigators
- Lead sponsor
- NoNO Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Calgary
- Responsible party
- Sponsor
- Investigators
- Michael D Hill, MD MSc, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02930018
- Sponsor's protocol ID
- NA-1-007
- Acronym
- ESCAPE-NA1
- Status last verified
- Oct 2022
- First submitted
- 6 Oct 2016
- Last updated
- 10 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23051991Cook 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.
PubMed 22388811Cook 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.
PubMed 23035045Sun 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.
PubMed 18617669Aarts 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.
PubMed 12399596Sattler 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.
PubMed 10364559Goyal 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.
PubMed 25671798Hill 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.
PubMed 32087818Stebner 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.
PubMed 40122606Ospel 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.
PubMed 39648909Ospel 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.
PubMed 38272571Fladt 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.
PubMed 38165335Singh 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.
PubMed 37165867Singh 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.
PubMed 37082967
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02930018
- Acronym / sponsor ID
- ESCAPE-NA1 / NA-1-007
- Conditions
- Stroke, Acute
- Keywords
- Acute Ischemic Stroke, Endovascular Thrombectomy, Neuroprotection, Tat-NR2B9c, NA-1, Nerinetide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,105 participants (actual)
- Lead sponsor
- NoNO Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of Calgary
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 20 Nov 2019 (actual)
- Study completion
- 20 Nov 2019 (actual)
- First posted
- 11 Oct 2016 (estimated)
- Results
- Posted 14 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Trial Objectives:
The primary objective is to determine the efficacy of the neuroprotectant, Nerinetide, in reducing global disability in subjects with major acute ischemic stroke (AIS) with a small established infarct core and with good collateral circulation selected for rapid endovascular revascularization.
The secondary objectives are to determine the efficacy of Nerinetide in:
- Reducing functional dependence
- Improving neurological outcome
- Improving activities of daily living
- Reducing mortality rate The leading safety objectives are to determine the effect of administering a dose of 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous (IV) infusion of Nerinetide to subject with acute stroke who are selected for endovascular revascularization on serious adverse events (SAEs) and 90-day mortality.
Trial Design:
This study is a Phase 3, randomized, multicentre, blinded, placebo-controlled, parallel group, single-dose design. Subjects harboring an acute ischemic stroke and who are selected for endovascular revascularization in accordance with local institutional practices and who harbor a small established infarct core and with good collateral circulation will be given a single, 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous dose of Nerinetide (NA-1) or placebo as soon as they are deemed to have met the enrollment criteria and with the intention of starting administration within 30 minutes of randomization. The randomization will be by stochastic minimization to balance baseline factors.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboDrug vehicle only |
| Nerinetide (NA-1), 2.6 mg/kg | Experimental | Drug: Nerinetide (NA-1), 2.6 mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nerinetide (NA-1), 2.6 mg/kgAlso: NA-1Single intravenous infusion of nerinetide over 10 ± 1 minutes | Drug | Nerinetide (NA-1), 2.6 mg/kg |
| PlaceboAlso: Drug vehicle onlyPlacebo Comparator: Placebo | Drug | Placebo |
Primary outcome
Number of Subjects With mRS Score of 0 to 2
Time frame: 90 Days
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.
2 secondary outcomes
Number of Subjects With NIHSS Score of 0 to 2
Time frame: 90 Days or the last rating
Mortality Rate
Time frame: 90 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23051991Hill 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: PubMed 22388811Cook 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: PubMed 23035045Cook 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: PubMed 18617669Sun 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: PubMed 12399596Aarts 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: PubMed 10364559Sattler 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: PubMed 25671798Goyal 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 publication: PubMed 32087818Hill 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.
- Derived from this study: PubMed 40122606Stebner 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.
- Derived from this study: PubMed 39648909Ospel 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.
- Derived from this study: PubMed 38272571Ospel 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.
- Derived from this study: PubMed 38165335Fladt 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael D Hill, MD MSc principal investigator
University of Calgary
50 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nerinetide (NA-1), 2.6 mg/kg in people with Stroke, Acute, run by NoNO Inc. at 50 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Canada, Germany, South Korea, Australia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With mRS Score of 0 to 2 (time frame: 90 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02930018, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2022.