NoNO-42 for Stroke

Recruiting at 8 trial locations

Overseen By Michael Tymianski, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NoNO Inc.

Disqualifiers: Pregnancy, Severe illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 91

Duration: 20 minutes

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a new treatment called NoNO-42 to determine its effectiveness for individuals who have experienced an acute ischemic stroke, a type of stroke caused by a blood clot blocking blood flow to the brain. Participants will be randomly assigned to receive either a dose of NoNO-42 or no additional treatment beyond standard care. The trial seeks individuals who have had a stroke within the last 4.5 hours, exhibit significant stroke symptoms, and did not require nursing care for daily activities before the stroke. The goal is to determine if NoNO-42 can improve recovery when administered shortly after a stroke. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that NoNO-42 is likely to be safe for humans?

Research shows limited safety information for treatments like NoNO-42. Although a similar treatment, NXY-059, has been studied, specific data on NoNO-42 remains scarce. This trial is in an early stage, aiming to determine if NoNO-42 is safe for stroke patients.

Earlier studies on NoNO-42 have focused on safety, tolerability, and pharmacokinetics. Researchers are closely monitoring for any side effects.

Testing NoNO-42 in a Phase 2 trial indicates initial signs of safety in earlier tests. However, more information is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke?

Unlike the standard treatments for stroke, which often involve medications like clot-busters or anticoagulants, NoNO-42 is unique because it delivers a targeted approach using a novel mechanism. It is administered as a quick 20-minute intravenous infusion, which allows for rapid action, aiming to start within just 10 minutes after randomization. Researchers are excited about NoNO-42 because this rapid delivery and onset could potentially minimize brain damage by intervening swiftly, offering a promising alternative to traditional therapies that may take longer to administer or become effective.

What evidence suggests that NoNO-42 might be an effective treatment for stroke?

Research shows that NoNO-42, which participants in this trial may receive, might help people who have had a stroke. In earlier studies with a similar treatment called Nerinetide, patients experienced less brain damage when they didn't receive other clot-busting drugs. Another study found that people treated with a related drug, NA-1, had fewer strokes visible on brain scans compared to those who received a placebo. While some results were not definitive, a study that combined results from several studies suggested that this approach is promising. Overall, these findings offer hope that NoNO-42 could effectively reduce brain damage from strokes. ^{1 6 7 8 9}

Who Is on the Research Team?

Bijoy Menon, MBBS, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for men and women aged 45 to 90 who've had a stroke recently (within the last 3 hours) and are eligible for clot-busting treatment or a procedure to remove the clot. They should have a moderate-to-severe stroke, be able to live independently before the stroke, and give informed consent.

Inclusion Criteria

I am chosen for clot-dissolving treatment for my stroke.

I was enrolled in the study within 3 hours of my symptoms starting.

I am between 45 and 90 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 hours

Treatment

Participants receive a single, 20-minute intravenous dose of NoNO-42 or placebo

20 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Multiple contacts over 90 days

What Are the Treatments Tested in This Trial?

Interventions

• NoNO-42

Trial Overview The NoNO-42 Trial tests whether a single dose of NoNO-42 can help people recovering from an acute ischemic stroke better than a placebo. Participants will either receive this new drug or a placebo alongside standard treatments like thrombolysis or thrombectomy.

How Is the Trial Designed?

Group I: NoNO-42 Active Control 1 Intervention

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.

Group II: Control Active Control 1 Intervention

Who Is Running the Clinical Trial?

NoNO Inc.

Lead Sponsor

Trials

7

Recruited

3,400+

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

Published Research Related to This Trial

In a systematic review of 25 studies, both L-arginine and nitric oxide (NO) donors significantly reduced the size of brain lesions caused by stroke in both permanent and transient models, indicating their potential efficacy in stroke treatment.

The administration of NO was associated with increased blood flow to the brain in permanent stroke models, suggesting that improved cerebral perfusion may help reduce stroke damage, although the narrow therapeutic time window for treatment could pose challenges in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow. Willmot, M., Gray, L., Gibson, C., et al.[2022]

Notoginsenoside R1 (NGR1) from Panax notoginseng shows neuroprotective effects against hypoxic-ischemic brain damage by enhancing neuronal survival and reducing apoptosis in primary cortical neurons, as demonstrated through various assays.

The protective effects of NGR1 are linked to the activation of the ATF6/Akt signaling pathway via estrogen receptors, as blocking these receptors with ICI-182780 negated the benefits of NGR1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Protective effect of notoginsenoside R1 on neuron injury induced by OGD/R through ATF6/Akt signaling pathway]. Hou, QL., Wang, Y., Li, YB., et al.[2018]

In a review of five trials involving 4,197 participants, nitric oxide donors (specifically glyceryl trinitrate) did not show overall benefits for stroke outcomes, but they did lower blood pressure by 7.4/3.3 mmHg.

When administered within 6 hours of stroke onset, nitric oxide donors were associated with improved functional outcomes and reduced mortality, suggesting a potential window for effective treatment in acute stroke cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials. Bath, PM., Woodhouse, L., Krishnan, K., et al.[2022]

Notoginsenoside R1 (R1) significantly reduces brain damage and neuronal loss while promoting neurogenesis and functional recovery in a rat model of ischemic stroke, indicating its potential as a neuroprotective agent.

The mechanism of R1's effects involves the activation of the BDNF/Akt/CREB signaling pathway, which enhances neuronal proliferation and recovery, suggesting it could be a promising treatment for long-term recovery after stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway. Zhu, T., Wang, L., Xie, W., et al.[2021]

Cilostazol has been shown to be more effective than aspirin for the secondary prevention of non-cardioembolic ischemic stroke, based on three clinical trials conducted in Japan and China.

Cilostazol also demonstrated a better safety profile, with significantly fewer major bleeding events compared to aspirin, suggesting it may be a safer alternative for stroke prevention in Asian patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cilostazol for secondary stroke prevention: an old dog with new tricks? Ansara, AJ., Shiltz, DL., Slavens, JB.[2018]

A comprehensive analysis of adverse events (AEs) from 5775 patients in acute ischemic stroke trials identified 132 expected AEs that accounted for 82.7% of reported events, primarily occurring within 10 days post-stroke.

Patient characteristics such as age, sex, baseline stroke severity, and multimorbidity status can modestly predict the incidence of AEs, helping to stratify patients by their risk for poststroke complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials. Hesse, K., Fulton, RL., Abdul-Rahim, AH., et al.[2022]

Nitric oxide (NO) is increasingly recognized for its positive role in stroke, acting as an essential gas signal molecule that can provide neuroprotective effects under specific conditions.

The effectiveness of NO in protecting against stroke is influenced by its concentration, the type of cells involved, and the timing of its release, highlighting the complexity of its role in both ischemic and hemorrhagic strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of nitric oxide in stroke. Chen, ZQ., Mou, RT., Feng, DX., et al.[2022]

The study developed the IschAEmic Stroke Calculator, an online tool that predicts the incidence of adverse events (AEs) in acute stroke trials based on patient characteristics, using data from the Virtual International Stroke Trials Archive (VISTA).

This calculator identifies 48 common AEs and allows researchers to compare predicted incidences with observed data, aiding in the interpretation of trial safety and potentially guiding preventive measures in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online Tool to Improve Stratification of Adverse Events in Stroke Clinical Trials. Hesse, K., MacIsaac, RL., Abdul-Rahim, AH., et al.[2021]

In the SENTIS Trial, which included 257 patients with ischemic stroke, the rates of neurological adverse events (AEs) were established, showing intracranial hemorrhage (ICnH) at 27.6%, cerebral edema at 6.6%, neurologic worsening at 18.3%, and new strokes at 4.7%.

Most neurological AEs occurred within defined timeframes, indicating that these rates can serve as benchmarks for safety assessments in future stroke trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurologic safety event rates in the SENTIS trial control population. Lutsep, HL., Altafullah, IM., Roberts, R., et al.[2013]

NXY-059G, when administered alone after an embolic stroke, significantly increased the hemorrhage rate in rabbits, suggesting it may compromise cerebral vascular integrity.

However, when NXY-059G was given in combination with the thrombolytic agent tPA, it reduced the incidence of tPA-induced hemorrhage, indicating a potential safety benefit when used together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the spin trap agent disodium- [tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (generic NXY-059) on intracerebral hemorrhage in a rabbit Large clot embolic stroke model: combination studies with tissue plasminogen activator. Lapchak, PA., Araujo, DM., Song, D., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06403267

NCT06403267 | NoNO-42 Trial in Acute Ischemic Stroke ... The secondary objectives are to determine the efficacy of NoNO-42 at 1 year post stroke in: Improving excellent functional outcome - Proportion of participants ...

2. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.048601?doi=10.1161/STROKEAHA.124.048601

Factors Influencing Nerinetide Effect on Infarct Volume in ... Nerinetide treatment was strongly associated with smaller final infarct volumes among patients not cotreated with alteplase.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23051991/

a phase 2, randomised, double-blind, placebo-controlled trial Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence ...

4. news-medical.net news-medical.net/news/20250219/Nerinetide-shows-promise-in-stroke-treatment-meta-analysis.aspx

Nerinetide shows promise in stroke treatment meta-analysis While the primary trials were inconclusive, the meta-analysis reveals that the data provide important clues for future research into stroke treatment.

5. cbc.ca cbc.ca/news/canada/prince-edward-island/pei-stroke-patients-research-study-9.6960731

Island stroke patients to be part of worldwide study on drug ... ... NoNO-42 can help prevent brain cell death. “What's happening during a stroke is that part of the brain is under a lot of stress and ...

6. ctv.veeva.com ctv.veeva.com/study/nono-42-trial-in-acute-ischemic-stroke-patients-selected-for-thrombolysis-with-or-without-endovascul

NoNO-42 Trial in Acute Ischemic Stroke Patients Selected for ... The NoNO-42 trial is a Phase 2b study for acute ischemic stroke patients, using NoNO-42 with or without thrombectomy, with 600 participants.

7. withpower.com withpower.com/trial/phase-2-stroke-acute-stroke-ischemic-4-2024-e8d37

NoNO-42 for Stroke · Recruiting Participants for Phase ... What safety data exists for NoNO-42 or similar treatments in humans? There is limited safety information available for NXY-059, a similar treatment, which ...

8. neuronewsinternational.com neuronewsinternational.com/nono-announces-first-patient-dosed-with-nono-42-in-phase-1-study/

NoNO announces first patient dosed with NoNO-42 in ... NoNO-42 is intended for the treatment of all people experiencing an acute ischaemic stroke. ... safety, tolerability and pharmacokinetics ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05636306

NCT05636306 | A Phase 1 Study to Evaluate Safety and ... The purpose of this clinical trial is to evaluate the safety, tolerability and pharmacokinetics of a single ascending intravenous dose of NoNO-42 administered ...