Trial Outcomes & Findings for Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis (NCT NCT04462536)

Last Updated: 2025-06-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

850 participants

Primary outcome timeframe

90 days

Results posted on

2025-06-22

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Vehicle only Placebo: Vehicle only	Nerinetide Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Overall Study STARTED	396	454
Overall Study Received Study Medication	393	451
Overall Study COMPLETED	391	441
Overall Study NOT COMPLETED	5	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Vehicle only Placebo: Vehicle only	Nerinetide Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Overall Study Withdrawal by Subject	3	9
Overall Study Lost to Follow-up	2	4

Baseline Characteristics

Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=393 Participants Vehicle only Placebo: Vehicle only	Nerinetide n=451 Participants Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes	Total n=844 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	94 Participants n=93 Participants	102 Participants n=4 Participants	196 Participants n=27 Participants
Age, Categorical >=65 years	299 Participants n=93 Participants	349 Participants n=4 Participants	648 Participants n=27 Participants
Age, Continuous	75 years STANDARD_DEVIATION 12.56 • n=93 Participants	76 years STANDARD_DEVIATION 13.29 • n=4 Participants	76 years STANDARD_DEVIATION 12.96 • n=27 Participants
Sex: Female, Male Female	194 Participants n=93 Participants	223 Participants n=4 Participants	417 Participants n=27 Participants
Sex: Female, Male Male	199 Participants n=93 Participants	228 Participants n=4 Participants	427 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	24 Participants n=93 Participants	38 Participants n=4 Participants	62 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) Black or African American	13 Participants n=93 Participants	18 Participants n=4 Participants	31 Participants n=27 Participants
Race (NIH/OMB) White	323 Participants n=93 Participants	362 Participants n=4 Participants	685 Participants n=27 Participants
Race (NIH/OMB) More than one race	15 Participants n=93 Participants	21 Participants n=4 Participants	36 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=93 Participants	10 Participants n=4 Participants	24 Participants n=27 Participants

PRIMARY outcome

Timeframe: 90 days

Population: ITT Population

Outcome measures

Outcome measures
Measure	Placebo n=396 Participants Vehicle only Placebo: Vehicle only	Nerinetide n=454 Participants Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Number of Participants With Independent Functioning on the Modified Rankin Scale (mRS), as Defined by a Score of 0-2	181 Participants	206 Participants

SECONDARY outcome

Timeframe: 90 days

Population: ITT Population

The estimand of mortality rate was the adjusted unconditional population difference in the number of deaths observed divided by the number of participants observed over the 90-day study period (mortality proportions) between treatment conditions (nerinetide vs. placebo) in the target patient population at Day 90. Deaths occurring over the Day 90 period were considered as non-responses.

Outcome measures

Outcome measures
Measure	Placebo n=396 Participants Vehicle only Placebo: Vehicle only	Nerinetide n=454 Participants Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Mortality Rate, as Defined by Event Rate (Percent) for Mortality Over the 90-day Study Period.	70 Participants	87 Participants

SECONDARY outcome

Timeframe: 90 days

Population: ITT Population

Worsening of stroke is defined as (A) progression, or hemorrhagic transformation of the index stroke, as documented by medical imaging that is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥4 point increase from lowest NIHSS during hospitalization or (B) results in death from the index stroke.

Outcome measures

Outcome measures
Measure	Placebo n=396 Participants Vehicle only Placebo: Vehicle only	Nerinetide n=454 Participants Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Number of Participants Exhibiting a Worsening of Their Index Stroke.	68 Participants	76 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=396 Participants Vehicle only Placebo: Vehicle only	Nerinetide n=454 Participants Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Number of Participants With Good Neurological Outcome, as Defined by a Score of 0-2 on the NIHSS at Day 90 Post Randomization.	251 Participants	268 Participants

Adverse Events

Placebo

Serious events: 148 serious events

Other events: 329 other events

Deaths: 70 deaths

Nerinetide

Serious events: 182 serious events

Other events: 393 other events

Deaths: 87 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=393 participants at risk Vehicle only Placebo: Vehicle only	Nerinetide n=451 participants at risk Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Infections and infestations Urinary Tract infection	11.7% 46/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	11.5% 52/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Vascular disorders Hypotension	9.2% 36/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	12.0% 54/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Nervous system disorders Haemorrhagic transformation stroke	9.9% 39/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	11.1% 50/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Nervous system disorders Headache	6.6% 26/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	11.5% 52/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Metabolism and nutrition disorders Hypokalaemia	8.7% 34/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	10.4% 47/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
General disorders pyrexia	9.2% 36/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	7.8% 35/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Respiratory, thoracic and mediastinal disorders Pneumonia aspriation	4.6% 18/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	5.3% 24/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Gastrointestinal disorders constipation	5.1% 20/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	8.0% 36/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Cardiac disorders Atrial fibrillation	3.8% 15/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	4.9% 22/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Infections and infestations Pneumonia	5.1% 20/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	2.9% 13/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Psychiatric disorders Delirium	5.3% 21/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	4.7% 21/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Cardiac disorders Bradycardia	4.6% 18/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	0.00% 0/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)

Additional Information

Michael Tymianski

NoNO Inc.

Phone: 6472932232

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=393 participants at risk Vehicle only Placebo: Vehicle only	Nerinetide n=451 participants at risk Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes Nerinetide: Single intravenous infusion of nerinetide 2.6 mg/kg (up to a maximum dose of 270 mg) over 10 ± 1 minutes
Nervous system disorders Stroke in Evolution	8.9% 35/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	6.4% 29/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Nervous system disorders ischaemic stroke	3.6% 14/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	4.9% 22/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	3.1% 12/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	2.9% 13/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Nervous system disorders Haemorrhagic transformation stroke	0.76% 3/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.8% 8/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Nervous system disorders Cerebral haemorrhage	0.76% 3/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.8% 8/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Infections and infestations Pneumonia	1.8% 7/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.8% 8/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Cardiac disorders Cardiac failure congestive	0.76% 3/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.8% 8/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Cardiac disorders Atrial fibrillation	0.51% 2/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.6% 7/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Metabolism and nutrition disorders Failure to thrive	1.8% 7/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.8% 8/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Vascular disorders various - combined	2.5% 10/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.8% 8/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) various-combined	1.5% 6/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	2.4% 11/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Injury, poisoning and procedural complications various - combined	1.3% 5/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	2.2% 10/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Psychiatric disorders various-combined	2.3% 9/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.1% 5/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
General disorders various - combined	0.76% 3/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	1.6% 7/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Renal and urinary disorders various	1.8% 7/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	0.67% 3/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Nervous system disorders others - combined	4.8% 19/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	6.9% 31/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Infections and infestations others - combined	4.6% 18/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	5.3% 24/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Respiratory, thoracic and mediastinal disorders others -combined	3.1% 12/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	4.0% 18/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Cardiac disorders others-combined	3.3% 13/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	3.5% 16/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)
Metabolism and nutrition disorders others-combined	0.00% 0/393 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)	0.67% 3/451 • TEAEs occurring within 30 days of randomization and all SAEs up to the end of study visit (Day 90 visit or death)