Clinical trial NCT02930018: Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stroke, Acute
Keywords: Acute Ischemic Stroke
Endovascular Thrombectomy
Neuroprotection
Tat-NR2B9c
NA-1
Nerinetide
Lead sponsor: NoNO Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Calgary
First posted: 2016-10-11
Enrollment: 1105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Acute ischemic stroke (AIS) for immediate endovascular treatment
2. Age 18 or greater.
3. Onset (last-seen-well) time to randomization time within 12 hours.
4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS) \> 5 at the time of randomization.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.

Exclusion Criteria:

1. Evidence of a large core of established infarction defined as ASPECTS 0-4.
2. Evidence of absence of collateral circulation on CTA (Collateral score of 0 or 1).
3. Intent to use any endovascular device other than a stent retriever or clot aspiration device or intra-arterial medications as the initial thrombectomy approach.
4. Intent to use any intravenous thrombolytic other than alteplase if intravenous thrombolysis is planned.
5. 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.
6. Estimated or known weight \> 120 kg or \< 45 kg.
7. Pregnancy; if a woman is of childbearing potential a urine or serum beta human chorionic gonadotropin (β-hCG) test is positive, or breastfeeding.
8. 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).
9. 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.
10. Prior enrolment in the ESCAPE-NA1 trial or prior receipt of NA-1 for any reason.
11. Severe known renal impairment defined as requiring dialysis (hemo- or peritoneal) or if known a creatinine clearance \< 29 mL/min.
12. Patient has a severe or fatal comorbid illness that will prevent improvement or follow-up.
13. 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).
14. Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding study inclusion.

Primary outcomes:
measure: Number of Subjects With mRS Score of 0 to 2
timeFrame: 90 Days
Secondary outcomes:
measure: Number of Subjects With NIHSS Score of 0 to 2
timeFrame: 90 Days or the last rating
measure: Mortality Rate
timeFrame: 90 Days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center - Davies Campus
state: California
city: Torrance
country: United States
facility: Providence Little Company of Mary Medical Center Torrance
state: California
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: Baptist Health Medical Center
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Marietta
country: United States
facility: WellStar Health Systems
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Brooklyn
country: United States
facility: NYU Lutheran Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Riverside Radiology
state: Ohio
city: Philadelphia
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Chattanooga
country: United States
facility: Chattanooga Center for Neurologic Research
state: Tennessee
city: Harlingen
country: United States
facility: Valley Baptist Medical Center
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center- Cherry Hill Campus
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: Calgary
country: Canada
facility: University of Calgary - Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Stroke Program Research Office/ Vancouver General Hosptial
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre- University Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Centre
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Hospital
state: Ontario
city: Montréal
country: Canada
facility: CHUM Hopital Notre-Dame
state: Quebec
city: Montréal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec- Universite Laval- Hopital de l'Enfant-Jesus
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresdner Neurovaskulares Centrum
city: Essen
country: Germany
facility: Klinik für Radiologie und Neuroradiologie
city: Göttingen
country: Germany
facility: University Medical Center Goettingen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Neurologische Klinik, Universität Heidelberg
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Mater Hospital
city: Daegu
country: Korea, Republic of
facility: Dongsan Medical Centre
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei Univ, Severence
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Stockholm
country: Sweden
facility: Karolinksa Institutet
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
Study officials:
affiliation: University of Calgary
name: Michael D Hill, MD MSc
role: PRINCIPAL_INVESTIGATOR
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citation: 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.
citation: 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.