NoNO-42 Trial in Acute Ischemic Stroke Patients Selected for Thrombolysis With or Without Endovascular Thrombectomy

Acute Ischemic Stroke Clinical Trial

Official title:

A Multicentre, Prospective, Randomized, Open Label, Blinded-Endpoint, Placebo-controlled, Single-dose Trial to Determine the Efficacy and Safety of NoNO-42 in Participants With Acute Ischemic Stroke Selected for Thrombolysis With or Without Endovascular Thrombectomy (ACT-42 Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06403267
• Other study ID #: NoNO42-02 (ACT-42)
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2024
• Est. completion date: May 2026

Study information

• Verified date: May 2024
• Source: NoNO Inc.
• Contact: Michael Tymianski, MD PhD
• Phone: +1 416-583-1687
• Email: mtymianski[@]nonoinc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ACT-42 is a domain of the ACT-GLOBAL platform (NCT06352632).

This trial is a Phase 2b, multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled single-dose adaptive trial.

A total of up to 600 male and female participants aged ≥ 45 to ≤ 90 years harboring an acute ischemic stroke who are eligible for an intravenous thrombolytic with or without endovascular thrombectomy therapy will be enrolled within 3 hours of stroke onset/last known well.

Description:

Because AIS is a medical emergency, the trial is designed to enable the administration of standard-of-care treatments in order to save the life of the person concerned, restore good health and alleviate suffering.

A total of up to 600 male and female participants aged ≥ 45 to ≤ 90 years harboring an acute ischemic stroke who are eligible for an intravenous thrombolytic with or without endovascular thrombectomy therapy will be enrolled within 3 hours of stroke onset/last known well. Randomization will be 1:1 drug/placebo. Randomization will be stratified by large vessel occlusion (LVO) (yes/no) and a minimization algorithm to minimize the contribution of imbalances in baseline factors (age, sex, baseline NIHSS score). The design is adaptive with prospective rules for adaptive enrichment, in which enrollment may be restricted to participants without an LVO. LVO is defined as an occlusion of the intracranial ICA, M1 or proximal M2.

Randomized participants will be given a single, 2.6 mg/kg 20-minute intravenous dose of NoNO-42 or placebo (placebo comprising normal saline infusion only) with a target start time of less than 10 minutes from randomization.

All participants will be followed for 90 days (or until death if prior to 90 days) for efficacy and 30 days for safety. The end of the trial is defined as the date that all participants have completed their Day 90 contact.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 600
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Acute ischemic stroke (AIS) selected for thrombolysis with or without EVT.

2. Onset (last-known-well) time to randomization time within 3 hours.

3. Ages = 45 to = 90 years.

4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS) > 5.

5. Confirmed symptomatic anterior circulation intracranial occlusion. Tandem extracranial carotid and intracranial occlusions are permitted.

6. Pre-stroke independent functional status in activities of daily living as judged by the enrolling physician. Patient must be living without requiring nursing care.

7. Consent process completed as per national laws and regulation and the applicable ethics committee requirements.

Exclusion Criteria:

1. Large extent early ischemic changes/infarct in the ischemic territory on qualifying imaging, defined as early ischemic changes on NCCT.

2. Any intracranial hemorrhage on qualifying imaging.

3. Unlikely to initiate study drug/placebo administration before arterial puncture in those selected for EVT.

4. Estimated or known weight > 115 kg (253 lbs).

5. Known/suspected pregnancy and/or lactation.

6. Systolic blood pressure < 90 mmHg

7. Known prior receipt of NoNO-42 for any reason, including prior enrolment in this trial.

8. Severe comorbid illness with life expectancy less than 90 days, or likely to prevent completing 90-day follow-up.

9. Long term care facility resident or prisoner

10. Participation in another clinical trial investigating a drug or medical device or a neuro-interventional or surgical procedure that is not considered as standard care in the 30 days preceding trial enrolment.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• NoNO-42
a single dose sterile 20 ml vial containing lyophilized powder for reconstitution containing 300 mg of NoNO-42 active ingredient.
• Placebo
100 ml 0.9% normal Saline

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
NoNO Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reducing global disability in participants with acute ischemic stroke (AIS)	A shift of one or more categories to reduced functional dependence analyzed across the whole distribution of outcomes on the modified Rankin Scale (mRS) at Day 90	90 days from intervention
Secondary	Improving excellent functional outcome	Proportion of participants with a mRS of 0-1 at Day 90	90 days from intervention
Secondary	Reducing worsening of stroke	Proportion of participants exhibiting a worsening of their index stroke during hospitalization.; Worsening of stroke is defined as (A) progression of the index stroke or symptomatic intracranial, or symptomatic intracranial hemorrhagic within the first 7-days after randomization, supported and confirmed 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 initial hospitalization or (B) results in death from the index stroke (i.e., index stroke is judged to be the principal cause of death) within the first 21-days after randomization.	90 days from intervention
Secondary	Reducing mortality rate	Proportion of participant mortality over the 90-day trial period	90 days from intervention
Secondary	Improving health-related quality of life	Health-related quality of life, as measured by the EQ-5D-5L at Day 90	90 days from intervention