Field Randomization of Nerinetide (NA-1) Therapy in Early Responders (FRONTIER)

May 11, 2023 updated by: NoNO Inc.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Intravenous NA-1 Initiated by Paramedics in the Field for Acute Cerebral Ischemia Within Three Hours of Symptom Onset

The purpose of this study is to determine whether nerinetide (NA-1) is effective in reducing global disability in patients with acute cerebral ischemia if administered early after symptom onset.

Study Overview

Status

Completed

Detailed Description

Nerinetide (NA-1) is being developed as an emergency drug aimed at reducing global disability in patients with acute cerebral ischemia if administered early after symptom onset.

The primary objective is to determine the efficacy of nerinetide in reducing global disability in patients with acute stroke. The secondary objectives are to determine the efficacy of nerinetide in reducing functional dependence, reducing mortality rate, reducing worsening of stroke, improving neurological outcome and improving activities of daily living.

The leading safety objectives are to determine the effect of administering a target dose of 2.60 mg/kg (up to a maximum dose of 270 mg) IV infusion of nerinetide within three hours of symptom onset by paramedics in the field on serious adverse events and 90-day mortality.

This trial is a multicenter, randomized, double-blind, placebo-controlled, single dose study initiated prehospital in the ambulance. It is being conducted using Emergency Medical Services (EMS) in Canada. Subjects with suspected acute stroke will be identified in the field by trained paramedics using the approved stroke protocol in use by the local EMS system, and further screened for eligibility and approval by an on-call trial physician. The paramedics will administer the study drug. Upon arrival at the emergency department, subjects will receive standard-of-care.

An Independent Data Monitoring Committee will perform safety reviews of the clinical data.

Study Type

Interventional

Enrollment (Actual)

532

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 Contact

Study Contact Backup

Study Locations

    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 1T2
        • Kelowna General Hospital
      • New Westminster, British Columbia, Canada, V3L 3W7
        • Royal Columbian Hospital
      • Vancouver, British Columbia, Canada, V5M 4X6
        • British Columbia Ambulance Service and British Columbia Emergency Health Services
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Vancouver General Hospital, Vancouver Coastal Health

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

40 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Provisional diagnosis of acute stroke as identified by paramedics using the local stroke triage tool
  • Respiratory rate 12-24 breaths per minute
  • Oxygen saturation ≥ 90% on room air
  • Systolic blood pressure < 90 or > 220 mmHg
  • Weight 45-120 kg
  • Last seen in usual state of health less than 3 hours before anticipated study drug initiation
  • Independently ambulatory with or without devices prior to event
  • LAMS score of 2-5 for at least 15 minutes and remains 2-5 at time of randomization

Exclusion Criteria:

  • Lack of IV access
  • Canadian Triage and Acuity Scale Level 1 and/or uncorrected airway, breathing or significant circulatory problem
  • Blood sugar < 3 mmol/L (< 55 mg/dL)
  • Seizure at onset of symptoms or observed by paramedic
  • Glasgow coma score of <10
  • Major head trauma in the last three months
  • Recent stroke in the last three months
  • Known or presumptive signs of pregnancy or breastfeeding
  • Prisoner
  • Long term care facility resident
  • Known advance directive to not resuscitate
  • Known participation in a clinical trial with an investigational drug or device within 30 days preceding this trial
  • Pre-existing neurologic, psychiatric, or advanced systemic condition that would preclude obtaining the neurological or functional outcome evaluations

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
Experimental: Nerinetide (NA-1)
2.60 mg/kg of nerinetide (up to a maximum dose of 270 mg) administered as a single 10 minute IV infusion using an ambulatory infusion pump early after stroke symptom onset.
Placebo Comparator: Placebo
Placebo administered as a single 10 minute IV infusion using an ambulatory infusion pump early after stroke symptom onset.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified Rankin Scale (mRS) scale
Time Frame: 90 days
The percentage of responders, using a sliding dichotomy on the mRS
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mRS shift analysis
Time Frame: 90 Days or the last rating
Shift to reduced functional dependence analyzed across the whole distribution of scores on the mRS
90 Days or the last rating
Mortality rate
Time Frame: 90 Days
A reduction in mortality as defined by event rate (proportion, expressed as a percentage)
90 Days
Worsening of stroke rate
Time Frame: 90 Days
A reduction in proportion of participants with worsening of stroke. Worsening of stroke is defined as progression, or hemorrhagic transformation, of the index stroke as documented in the study CRF that (i) is deemed life-threatening and/or (ii) results in increased disability as gauged by a ≥4 point increase from lowest NIHSS during hospitalization and/or (iii) results in death.
90 Days
National Institutes of Health Stroke Scale (NIHSS)
Time Frame: 90 Days or the last rating
Proportion of subjects with good neurological outcome, as defined by a score of 0-1 on the NIHSS
90 Days 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 Barthel Index
90 Days or the last rating

Collaborators and Investigators

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

Sponsor

Investigators

  • Principal Investigator: Jim Christenson, M.D., University of British Columbia
  • Principal Investigator: Richard Swartz, M.D., Sunnybrook Health Sciences Centre

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 26, 2015

Primary Completion (Actual)

March 27, 2023

Study Completion (Actual)

March 27, 2023

Study Registration Dates

First Submitted

December 5, 2014

First Submitted That Met QC Criteria

December 10, 2014

First Posted (Estimate)

December 11, 2014

Study Record Updates

Last Update Posted (Actual)

May 12, 2023

Last Update Submitted That Met QC Criteria

May 11, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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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