A study to test if a single dose of nerinetide can reduce neurological disability in people who have had a stroke and who are selected for endovascular therapy (a procedure using a device that removes the blood clot (thrombus) from a blood vessel in the brain)

• Register: EUCTR
• Last refreshed on: 21 June 2021
• Main ID: EUCTR2020-002360-30-NL
• Date of registration: 14/06/2021
• Prospective Registration: Yes
• Primary sponsor: NoNO Inc.
• Public title: A study to test if a single dose of nerinetide can reduce neurological disability in people who have had a stroke and who are selected for endovascular therapy (a procedure using a device that removes the blood clot (thrombus) from a blood vessel in the brain)
• Scientific 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 (ESCAPE-NEXT Trial) - ESCAPE-NEXT
• Target sample size: 1020
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002360-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Germany, Italy, Netherlands, Norway, Singapore, Switzerland, United States

Contacts

• Name: Yatika Kohli
• Affiliation: NoNO Inc.

• Name: Yatika Kohli
• Affiliation: NoNO Inc.

Key inclusion & exclusion 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)
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 510
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 510

Exclusion criteria:
1) Treated 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 (264 lbs)
10) Pregnancy/Lactation; female, with positive urine or serum beta human chorionic gonadotropin (ß-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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acute ischemic stroke (AIS)
MedDRA version: 22.1 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 22.1 Level: LLT Classification code 10055221 Term: Ischemic stroke System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 22.1 Level: LLT Classification code 10023027 Term: Ischaemic stroke NOS System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 22.1 Level: LLT Classification code 10074321 Term: Nonhaemorrhagic stroke System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 22.1 Level: LLT Classification code 10074318 Term: Nonhemorrhagic stroke System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Nerinetide
Product Code: NA-1
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: Nerinetide
CAS Number: 500992-11-0
Current Sponsor code: NA-1/Tat-NR2B9c
Other descriptive name: Nerinetide hydrochloride
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Concentrate for solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: The primary objective is to determine the efficacy of the neuroprotectant, nerinetide in:

• Reducing global disability in participants with acute ischemic
stroke (AIS)

Primary end point(s): Reducing global disability in participants with acute ischemic stroke (AIS).

The proportion of participants with independent functioning on the modified Rankin Scale (mRS), as defined by a score of 0-2 at Day 90.

Secondary Objective: The secondary objectives are to determine the efficacy of nerinetide in:
1) Reducing mortality rate
2) Improving neurological outcome
3) Reducing worsening of stroke*
4) Reducing functional dependence

* 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.

Timepoint(s) of evaluation of this end point: Day 90

Secondary Outcome(s)

Secondary end point(s): Reducing mortality rate.

Improving neurological outcome.

Reducing worsening of stroke.

Reducing functional dependence.

Proportion of participant mortality over the 90-day study period.

Proportion of participants with a score of 0-2 on the NIHSS at Day 90 .

Proportion of participants with a worsening of stroke over the 90-day study period.

A shift of one or more categories to reduced functional dependence analyzed across the whole distribution of outcomes on the mRS at Day 90.

Timepoint(s) of evaluation of this end point: Day 90

Secondary ID(s)

2020-002360-30-DE

NA-1-009

NCT04462536

Source(s) of Monetary Support

NoNO Inc.