The primary objective is to determine the efficacy of the neuroprotectant, nerinetide in:• Reducing global disability in participants with acute ischemic stroke (AIS)
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Reducing global disability in participants with acute ischemic stroke (AIS).
Secondary outcome
The secondary objectives are to determine the efficacy of nerinetide in:
• Reducing mortality rate
• Improving activities of daily living
• Improving health related quality of life
Background summary
Nerinetide (NA-1) is a first in class neuroprotectant that is designed to
address the major unmet medical need for treatments that reduce the functional
disability produced by acute stroke. It reduces the vulnerability of ischemic
brain tissue to hypoperfusion by targeting neurotoxic pathways that lead to
ischemic neuronal death. Nerinetide is intended, alone or in combination with
available therapies, to treat acute stroke, a serious and life-threatening
disease. For this reason, nerinetide is being developed as a drug for use in
emergency situations aimed at reducing global disability in patients with acute
ischemic stroke. Nerinetide may provide significant benefit for the treatment
of acute cerebral ischemia if administered to stroke patients
who present to medical attention before infarction is complete.
Study objective
The primary objective is to determine the efficacy of the neuroprotectant,
nerinetide in:
• Reducing global disability in participants with acute ischemic stroke (AIS)
Study design
This study is a Phase 3, randomized, multicentre, blinded, placebocontrolled,
parallel group, single-dose design with a single
interim analysis for safety and efficacy.
Because AIS 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. Randomization will be
stratified by time from stroke onset to randomization <=4.5 hours (yes/no) and
done with stochastic minimization to balance baseline factors within strata.
Outcomes of the main trial will be evaluated throughout a 90 day observation
period.
Participants will be contacted by telemedicine or telephone at 1-Year by
individuals blinded to the outcome of the main trial.
Two database locks and corresponding reports are planned for this trial. The
first report will be based on the completion of Day 90 visits
for the main trial. The second report will be following the completion of the
1-Year follow up for the analytic sub-trial.
Intervention
Nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg or matching placebo
volume) will be administered as a single 10±1minute
intravenous infusion using an infusion pump starting after randomization.
Study burden and risks
Increase in hypotension (drop in blood pressure) within 2 hours after receiving
nerinetide. The drop in blood pressure was temporary but may require treatment
or monitoring.
Wellington Street West 479A
Toronto M5V 1E7
CA
Wellington Street West 479A
Toronto M5V 1E7
CA
Listed location countries
Age
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)
a. NIHSS > 5 for internal carotid artery (ICA) and M1-middle cerebral
artery (MCA) occlusion or
b. 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) Treatment with a tissue 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
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-002360-30-NL |
| ClinicalTrials.gov | NCT04462536 |
| CCMO | NL77356.078.21 |