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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02930018
Recruitment Status : Completed
First Posted : October 11, 2016
Results First Posted : December 14, 2020
Last Update Posted : October 10, 2022
Sponsor:
Collaborator:
University of Calgary
Information provided by (Responsible Party):
NoNO Inc.

Tracking Information
First Submitted Date  ICMJE October 6, 2016
First Posted Date  ICMJE October 11, 2016
Results First Submitted Date  ICMJE October 22, 2020
Results First Posted Date  ICMJE December 14, 2020
Last Update Posted Date October 10, 2022
Actual Study Start Date  ICMJE March 1, 2017
Actual Primary Completion Date November 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2016)
Modified Rankin Score (mRS) [ Time Frame: 90 Days ]
Overall proportion of subjects experiencing a favorable functional outcome 90 days post-randomization, defined as 0 to 2 on the mRS
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2020)
  • 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.
  • Mortality Rate [ Time Frame: 90 Days ]
    Mortality rate, as defined by event rate (%) for mortality over the 90-day study period
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2016)
  • mRS Shift Analysis [ Time Frame: 90 Days or the last rating ]
    Shift of one or more categories to reduced functional dependence analyzed across the whole distribution of scores on the mRS at Day 90 or the last rating.
  • NIHSS [ Time Frame: 90 Days or the last rating ]
    Proportion of subjects with good neurological outcome, as defined by a score of 0-2 on the NIHSS at Day 90 or the last rating.
  • Barthel Index [ Time Frame: 90 Days or the last rating ]
    Proportion of subjects with functional independence in activities of daily living, as defined by a score of ≥ 95 on the BI at Day 90 or the last rating.
  • Mortality Rate [ Time Frame: 90 Days ]
    A reduction in mortality rate, as defined by event rate (%) for mortality over the 90-day study period
  • Functional Independence based on mRS [ Time Frame: 90 Days or the last rating ]
    Proportion of subjects with functional independence, as defined by a score of 0-1 on the mRS at Day 90 or the last rating.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: October 7, 2016)
  • EQ-5D-5L [ Time Frame: 90 Days or the last rating ]
    Health-related quality of life, as measured by the EQ-5D-5L at Day 90 or the last rating.
  • Stroke Volume [ Time Frame: 24 hour follow up ]
    Volume of stroke as measured by MRI. If NCCT was done instead of MRI, Volume of stroke will be derived from hypodense areas.
  • Test of language function [ Time Frame: 90 Days ]
    Cognitive outcome - The 15-item Boston Naming Test (BNT15)
  • Test of hemi-spatial neglect [ Time Frame: 90 Days ]
    Cognitive Outcome - Sunnybrook hemi-spatial neglect procedure (SNAP)
  • Global test of cognitive function. Scale from 0 to 30 points. [ Time Frame: 90 Days ]
    Cognitive outcome - The Montreal Cognitive Assessment (MoCA)
  • Functional outcome based on mRS [ Time Frame: 30 days ]
    The proportion of subjects experiencing a favorable functional outcome 30 days post-randomization, defined as 0 to 2 on the mRS.
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Stroke, Acute
Intervention  ICMJE
  • Drug: Nerinetide (NA-1), 2.6 mg/kg
    Single intravenous infusion of nerinetide over 10 ± 1 minutes
    Other Name: NA-1
  • Drug: Placebo
    Placebo Comparator: Placebo
    Other Name: Drug vehicle only
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Drug vehicle only
    Intervention: Drug: Placebo
  • Experimental: Nerinetide (NA-1), 2.6 mg/kg
    Intervention: Drug: Nerinetide (NA-1), 2.6 mg/kg
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 16, 2020)
1105
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2016)
1120
Actual Study Completion Date  ICMJE November 20, 2019
Actual Primary Completion Date November 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Germany,   Ireland,   Korea, Republic of,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02930018
Other Study ID Numbers  ICMJE NA-1-007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party NoNO Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE NoNO Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE University of Calgary
Investigators  ICMJE
Principal Investigator: Michael D Hill, MD MSc University of Calgary
PRS Account NoNO Inc.
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP