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

Phase 2

Recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: NoNO-42

• Registration Number: NCT06403267
• Lead Sponsor: NoNO Inc.

Brief 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 ≥ 18 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 4.5 hours of stroke onset/last known well.

Detailed 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 ≥ 18 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 4.5 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 receive/received an intravenous thrombolytic and be allocated to:

* the investigational group, a single, 2.6 mg/kg (up to a maximum of 300 mg) 20-minute intravenous dose of NoNO-42, with a target start time of less than 10 minutes from randomization or

* the control group, no trial specific intervention.

Day 90: 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.

1-Year follow Up: participants who completed the trial to Day 90 may be followed at 1 year for long-term efficacy.

One database lock and corresponding report for the trial to Day 90 and a separate database lock and analysis for the 1-year follow up are planned.

Study Timeline

• Study First Submitted: 2024-04-26
• Study First Submitted QC: 2024-05-06
• Study First Posted: 2024-05-07
• Study Start: 2024-10-02
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-10
• Last Update Posted: 2025-07-15
• Primary Completion: 2026-12
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. Confirmed or suspected acute ischemic stroke (AIS) selected for intravenous thrombolysis.
2. Onset (last-known-well) time to randomization time within 4.5 hours.
3. Ages ≥ 18 to ≤ 90 years.
4. Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS) >5.
5. Confirmed or suspected 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.
2. Any intracranial hemorrhage on qualifying imaging.
3. Unlikely to initiate study drug administration before arterial puncture in those selected for EVT.
4. Known/suspected pregnancy and/or lactation.
5. Systolic blood pressure < 90 mmHg
6. 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 outside of the ACT-GLOBAL platform 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NoNO-42	NoNO-42	Randomized participants will be given a single, 2.6 mg/kg 20-minute intravenous dose of NoNO-42 with a target start time of less than 10 minutes from randomization.

Primary Outcome Measures

Name	Time	Method
Reducing global disability in participants with acute ischemic stroke (AIS)	90 days from intervention	The primary outcome is the mRS at Day 90. The primary analysis of the primary outcome will be a "shift" analysis, which is an ordinal analysis across the mRS scale. The primary estimand is odds-ratio for a better outcome on the mRS scale for NoNO-42 compared to control.

Secondary Outcome Measures

Name	Time	Method
Improving excellent functional outcome	90 days from intervention	Proportion of participants with a mRS of 0-1 at Day 90
Reducing worsening of stroke	90 days from intervention	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.
Improving functional independence	90 days from intervention	Proportion of participants with a mRS of 0-2 at Day 90.
Reducing mortality rate	90 days from intervention	Proportion of participant mortality over the 90-day trial period
Improving health-related quality of life	90 days from intervention	Health-related quality of life, as measured by the EQ-5D-5L at Day 90

Trial Locations

Locations (9)

University of Calgary - Foothills Medical Centre; 🇨🇦 Calgary, Alberta, Canada

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

University of Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

Ottawa Hospital Research Institute; 🇨🇦 Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Unity Health Toronto, St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Royal University Hospital; 🇨🇦 Saskatoon, Saskatchewan, Canada