Clinical trial NCT06403267: NoNO-42 Trial in Acute Ischemic Stroke Patients Selected for Thrombolysis with or Without Endovascular Thrombectomy
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Keywords: Thrombolysis, Endovascular thrombectomy
Lead sponsor: NoNO Inc.
Sponsor class: INDUSTRY
First posted: 2024-05-07
Enrollment: 600
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, open label, blinded-endpoint (PROBE) controlled single-dose adaptive trial
Primary purpose: TREATMENT

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 ≥ 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.

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 ≥ 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Reducing global disability in participants with acute ischemic stroke (AIS)
timeFrame: 90 days from intervention
Secondary outcomes:
measure: Improving excellent functional outcome
timeFrame: 90 days from intervention
measure: Reducing worsening of stroke
timeFrame: 90 days from intervention
measure: Reducing mortality rate
timeFrame: 90 days from intervention
measure: Improving health-related quality of life
timeFrame: 90 days from intervention
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary - Foothills Medical Centre
state: Alberta
Study officials:
affiliation: University of Calgary
name: Bijoy Menon, MBBS, MD
role: STUDY_CHAIR
References: