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Trial record 1 of 1 for:    04462536
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Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis (ESCAPE-NEXT)

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ClinicalTrials.gov Identifier: NCT04462536
Recruitment Status : Recruiting
First Posted : July 8, 2020
Last Update Posted : December 17, 2020
Sponsor:
Collaborator:
University of Calgary
Information provided by (Responsible Party):
NoNO Inc.

Brief Summary:
The primary purpose of this study is to determine if a single dose of nerinetide can reduce neurological disability in people who have had a stroke and are selected for endovascular therapy without the use of a tissue plasminogen activator (alteplase, tenecteplase, or equivalent).

Condition or disease Intervention/treatment Phase
Stroke, Acute Drug: Placebo Drug: Nerinetide Phase 3

Detailed Description:

This study is a Phase 3, randomized, multicentre, blinded, placebo-controlled, parallel group, single-dose, adaptive design with a single interim analysis for unblinded sample size re-estimation. Because AIS (acute ischemic stroke) is a medical emergency, the trial is designed to enable the administration of standard-of-care treatments without delay in order to save the life of the person concerned, restore good health or alleviate suffering.

Participants harboring an acute ischemic stroke who are selected for endovascular revascularization without intravenous or intra-arterial thrombolytic therapy will be given a single, 2.6 mg/kg (up to a maximum dose of 270 mg) intravenous dose of nerinetide or placebo. Outcomes of the main trial will be evaluated throughout a 90 day observation period.

Participants will be followed at 1-Year for the analytic sub-trial for further outcome assessment by telemedicine or telephone interview conducted by individuals blinded to the outcome of the main trial. This sub-trial will be conducted to explore the independent functioning and quality of life at 1-Year.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1020 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis
Actual Study Start Date : December 6, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Arm Intervention/treatment
Placebo Comparator: Placebo
Vehicle only
Drug: Placebo
Vehicle only

Experimental: Nerinetide
Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Drug: Nerinetide
Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Other Name: NA-1




Primary Outcome Measures :
  1. Number of participants with independent functioning on the modified Rankin Scale (mRS), as defined by a score of 0-2 [ Time Frame: 90 days ]
    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.


Secondary Outcome Measures :
  1. Mortality rate, as defined by event rate (percent) for mortality over the 90-day study period. [ Time Frame: 90 days ]
  2. Number of participants with good neurological outcome, as defined by a score of 0-2 on the NIHSS at Day 90 post randomization. [ Time Frame: 90 days ]
    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.

  3. Number of participants exhibiting a worsening of their index stroke. [ Time Frame: 90 days ]
    Worsening of stroke is defined as progression, or hemorrhagic transformation of the index stroke, as documented by medical imaging, and that is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥4 point increase from lowest NIHSS pre decline and/or (c) results in death.

  4. A shift of one or more categories to reduced functional dependence analyzed across the whole distribution of outcomes on the mRS at Day 90 post randomization. [ Time Frame: 90 days ]
    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.


Other Outcome Measures:
  1. Volume of stroke as measured by MRI or CT brain imaging (MRI preferred) [ Time Frame: 90 days ]
  2. Number of participants with functional independence in activities of daily living, as defined by a score of ≥ 95 on the Barthel Index (BI) at Day 90 post randomization. [ Time Frame: 90 days ]
    The BI is an index of functional independence that is a valid measure of activities of daily living when employed in stroke trials. Modified BI scores range from 0 to 100, with higher scores indicating greater independence in activities of daily living and mobility.

  3. Number of participants with reduced moderate or severe disability or death, as defined by a score of 4-6 on the mRS at Day 90 post randomization. [ Time Frame: 90 days ]
    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.

  4. Number of participants with excellent functional outcome, as defined by a score of 0-1 on the mRS at Day 90 post randomization. [ Time Frame: 90 days ]
    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.

  5. Health-related quality of life, as measured by the EQ-5D-5L at Day 90. [ Time Frame: 90 days ]
    The EQ-5D-5L (EuroQol 5-Dimensional 5-Level) is a generic instrument for describing and valuing health. It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems. The respondents will also rate their overall health on the day of the interview on a 0-100 visual analogue scale (EQ-VAS, higher scores mean better outcomes).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Acute ischemic stroke (AIS) selected for emergency endovascular treatment.
  2. Age 18 years or greater.
  3. Onset (last-known-well) time to randomization time within 12 hours.
  4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS):

    1. NIHSS > 5 for internal carotid artery (ICA) and M1-middle cerebral artery (MCA) occlusion; or
    2. NIHSS > 10 for M2-MCA occlusion.
  5. Confirmed symptomatic intracranial occlusion at one or more of the following locations: Intracranial carotid I/T/L, M1 or M2 segment MCA. Tandem extracranial carotid and intracranial occlusions are permitted.
  6. Pre-stroke (24 hours prior to stroke onset) independent functional status in activities of daily living with modified Barthel Index (BI) ≥ 95. Patient must be living without requiring nursing care.
  7. Qualifying imaging performed less than 2 hours prior to randomization.
  8. Consent process completed as per national laws and regulation and the applicable ethics committee requirements.

Exclusion Criteria:

  1. Treated with an intravenous or intra-arterial plasminogen activator (e.g., alteplase or tenecteplase) within 24 hours before randomization.
  2. Determination by the treating physician, based on current treatment guidelines and medical evidence, that treatment with a plasminogen activator is indicated.
  3. Evidence of a large core of established infarction defined as ASPECTS 0-4.
  4. Evidence of absence of collateral circulation on qualifying imaging (collateral score of 0 or 1).
  5. Any evidence of intracranial hemorrhage on the qualifying imaging.
  6. Planned use of an endovascular device not having approval or clearance by the relevant regulatory authority.
  7. Endovascular thrombectomy procedure is completed as defined by the presence of TICI 2c/3 reperfusion or completion of groin / arterial closure.
  8. Clinical history, past imaging or clinical judgment suggesting that the intracranial occlusion is chronic or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention.
  9. Estimated or known weight > 120 kg (264 lbs).
  10. Pregnancy/Lactation; female, with positive urine or serum beta human chorionic gonadotropin (β-hCG) test, or breastfeeding.
  11. Known prior receipt of nerinetide for any reason, including prior enrolment in this ESCAPE-NEXT trial.
  12. Severe known renal impairment defined as requiring renal replacement therapy (hemo- or peritoneal dialysis).
  13. Severe or fatal comorbid illness that will prevent improvement or follow up.
  14. Inability to complete follow-up treatment to Day 90.
  15. Participation in another clinical trial investigating a drug, medical device, or a medical procedure in the 30 days preceding trial inclusion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04462536


Contacts
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Contact: Michael Tymianski, MD PhD 4165831687 mtymianski@nonoinc.ca
Contact: Kathy Heard, MSc 4165831687 kheard@nonoinc.ca

Locations
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Canada, Alberta
Foothills Medical Centre - University of Calgary Recruiting
Calgary, Alberta, Canada, T2N2T9
Contact: Andrew Demchuk, M.D.    (403) 944-8671    ademchuk@ucalgary.ca   
Sponsors and Collaborators
NoNO Inc.
University of Calgary
Investigators
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Principal Investigator: Michael D. Hill M.D., MSc Study Principal Investigator, University of Calgary
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Responsible Party: NoNO Inc.
ClinicalTrials.gov Identifier: NCT04462536    
Other Study ID Numbers: NA-1-009
First Posted: July 8, 2020    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases