Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1)

October 6, 2022 updated by: NoNO Inc.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1105

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia
        • Royal Adelaide Hospital
      • Parkville, Australia
        • Royal Melbourne Hospital
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N2T9
        • University of Calgary - Foothills Medical Centre
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Vancouver Stroke Program Research Office/ Vancouver General Hosptial
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 3A7
        • Queen Elizabeth II Health Science Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Hamilton General Hospital
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Centre- University Hospital
      • Ottawa, Ontario, Canada, K1Y 4E9
        • The Ottawa Hospital
      • Toronto, Ontario, Canada, M5B 1W8
        • St Michael's Hospital
      • Toronto, Ontario, Canada, M5T 2S8
        • University Health Network - Toronto Western Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Centre
    • Quebec
      • Montréal, Quebec, Canada, H2L 4M1
        • CHUM Hopital Notre-Dame
      • Montréal, Quebec, Canada, H3A1A1
        • Montreal Neurological Institute and Hospital
      • Quebec City, Quebec, Canada, G1J 1Z4
        • CHU de Quebec- Universite Laval- Hopital de l'Enfant-Jesus
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Royal University Hospital
  • Germany
      • Dresden, Germany, 01307
        • Universitätsklinikum Carl Gustav Carus Dresdner Neurovaskulares Centrum
      • Essen, Germany, D - 45131
        • Klinik für Radiologie und Neuroradiologie
      • Göttingen, Germany, 37075
        • University Medical Center Goettingen
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Heidelberg, Germany, 69120
        • Neurologische Klinik, Universität Heidelberg
  • Ireland
      • Dublin, Ireland
        • Beaumont Hospital
      • Dublin, Ireland
        • Mater Hospital
  • Korea, Republic of
      • Daegu, Korea, Republic of
        • Dongsan Medical Centre
      • Incheon, Korea, Republic of
        • Inha University Hospital
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Yonsei Univ, Severence
  • Sweden
      • Lund, Sweden
        • Skane University Hospital
      • Stockholm, Sweden, 17176
        • Karolinksa Institutet
  • United Kingdom
      • Belfast, United Kingdom
        • Royal Victoria Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Ronald Reagan UCLA Medical Center
      • San Francisco, California, United States, 94114
        • California Pacific Medical Center - Davies Campus
      • Torrance, California, United States, 90503
        • Providence Little Company of Mary Medical Center Torrance
    • Colorado
      • Englewood, Colorado, United States, 80110
        • Swedish Medical Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Baptist Health Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Grady Memorial Hospital
      • Marietta, Georgia, United States, 30060
        • Wellstar Health Systems
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Medical School
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
    • New York
      • Brooklyn, New York, United States, 11220
        • NYU Lutheran Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Novant Health Forsyth Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43214
        • Riverside Radiology
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19001
        • Abington Memorial Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Presbyterian
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Chattanooga Center for Neurologic Research
    • Texas
      • Harlingen, Texas, United States, 78550
        • Valley Baptist Medical Center
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center- Cherry Hill Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug vehicle only
Drug: Placebo
Placebo Comparator: Placebo
Other Names:
  • Drug vehicle only
Experimental: Nerinetide (NA-1), 2.6 mg/kg
Drug: Nerinetide (NA-1), 2.6 mg/kg
Single intravenous infusion of nerinetide over 10 ± 1 minutes
Other Names:
  • NA-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
90 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With NIHSS Score of 0 to 2
Time Frame: 90 Days or the last rating

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.
90 Days or the last rating
Mortality Rate
Time Frame: 90 Days
Mortality rate, as defined by event rate (%) for mortality over the 90-day study period
90 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NoNO Inc.

Collaborators

University of Calgary

Investigators

  • Principal Investigator: Michael D Hill, MD MSc, University Of Calgary

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2017

Primary Completion (Actual)

November 20, 2019

Study Completion (Actual)

November 20, 2019

Study Registration Dates

First Submitted

October 6, 2016

First Submitted That Met QC Criteria

October 7, 2016

First Posted (Estimate)

October 11, 2016

Study Record Updates

Last Update Posted (Actual)

October 10, 2022

Last Update Submitted That Met QC Criteria

October 6, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NA-1-007

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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