NoNO-42 for Stroke

Overseen By Michael Tymianski, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NoNO Inc.

Disqualifiers: Pregnancy, Severe illness, others

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

Trial Summary

What is the purpose of this trial?

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.

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.

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 has been studied in combination with another stroke treatment. The study looked at effects on bleeding and brain damage, as well as blood sugar and body temperature, but detailed safety results are not provided. ^{1 2 3 4 5}

How does the drug NoNO-42 for stroke differ from other treatments?

NoNO-42 is unique because it may involve components like Notoginsenoside R1, which promotes brain recovery by encouraging new brain cell growth through specific pathways (BDNF/Akt/CREB). This is different from other treatments like nitric oxide donors, which focus on improving blood flow and reducing blood pressure shortly after a stroke. ^{6 7 8 9 10}

Research Team

Bijoy Menon, MBBS, MD

Principal Investigator

University of Calgary

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

NoNO Inc.

Lead Sponsor

Trials

7

Recruited

3,400+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Online Tool to Improve Stratification of Adverse Events in Stroke Clinical Trials. [2021]

2. Denmark pubmed.ncbi.nlm.nih.gov

Neurologic safety event rates in the SENTIS trial control population. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Use of cilostazol for secondary stroke prevention: an old dog with new tricks? [2018]

5. United States 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. [2019]

6. United States 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. [2022]

7. China pubmed.ncbi.nlm.nih.gov

[Protective effect of notoginsenoside R1 on neuron injury induced by OGD/R through ATF6/Akt signaling pathway]. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway. [2021]

9. United States 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. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

The role of nitric oxide in stroke. [2022]