Azetukalner for Depression

(X-NOVA3 Trial)

Recruiting at 20 trial locations

Overseen By Xenon Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Xenon Pharmaceuticals Inc.

Must not be taking: Antidepressants, Benzodiazepines

Disqualifiers: Bipolar, Schizophrenia, PTSD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

1 Power Preferred Clinic 1 of this trial's clinic is considered top 20 on Power

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called azetukalner to determine its effectiveness for Major Depressive Disorder (MDD). The goal is to assess whether azetukalner is safe and effective when used alone for treating depression. Participants will receive either azetukalner or a placebo (a pill with no active medicine) to compare results. Eligible participants must have experienced major depression for at least 6 weeks but not more than 24 months and must not have other mood disorders. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for depression.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking antidepressants and certain other medications like benzodiazepines at least 2 weeks before joining the trial (4 weeks for fluoxetine).

Is there any evidence suggesting that azetukalner is likely to be safe for humans?

Research shows that azetukalner has been tested for its safety and effectiveness in treating major depressive disorder. Studies indicate that azetukalner is generally safe and well-tolerated by patients. Specifically, research highlights that no new safety issues emerged during long-term use, suggesting that most people do not experience serious side effects.

These findings are supported by studies where patients taking azetukalner did not report any unexpected problems, increasing confidence in the treatment's safety. As always, discussing this information with a healthcare provider can help determine if joining a trial is appropriate. ^{1 2 3 4 5}

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

Azetukalner is unique because it targets a different pathway in the brain compared to most current depression treatments, which often focus on serotonin levels. Researchers are excited about Azetukalner because it operates on the glutamate system, potentially offering faster relief from depressive symptoms. Unlike traditional antidepressants, which can take weeks to become effective, Azetukalner might show positive results in a shorter timeframe, providing quicker hope for those struggling with depression.

What evidence suggests that azetukalner might be an effective treatment for depression?

Research has shown that azetukalner, which participants in this trial may receive, may help treat Major Depressive Disorder (MDD). Studies found that people taking azetukalner experienced a significant reduction in depressive symptoms compared to those taking a placebo. Specifically, patients showed a meaningful drop in their scores on a test measuring depression severity. Improvements appeared early in the treatment, with a noticeable decrease in the loss of pleasure in activities. Azetukalner works by opening certain channels in the brain, which may help regulate mood. Overall, this treatment shows potential as an effective option for those with depression. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with Major Depressive Disorder (MDD) who have been diagnosed by a healthcare professional. Participants must be willing to take the study medication and follow the trial procedures. Specific details about what makes someone eligible or not are not provided here.

Inclusion Criteria

Have you been feeling consistently depressed for at least 6 weeks?

Exclusion Criteria

Have you been diagnosed with Bipolar Disorder?

Have you been diagnosed with Obsessive-Compulsive Disorder

Have you been diagnosed with Schizophrenia?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azetukalner or placebo as a monotherapy for Major Depressive Disorder

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azetukalner

Trial Overview The X-NOVA3 study is testing Azetukalner against a placebo to see if it's effective and safe as a single treatment for MDD. It's in Phase 3, which means they're looking at how well it works on a larger scale after some safety has already been shown.

How Is the Trial Designed?

Group I: Azetukalner Experimental Treatment 1 Intervention

Azetukalner 20 mg

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Xenon Pharmaceuticals Inc.

Lead Sponsor

Trials

19

Recruited

3,400+

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2834419

Azetukalner, a Novel KV7 Potassium Channel Opener, in ... The primary objective was to assess the efficacy of 10 mg and 20 mg of azetukalner compared with placebo for improvement of depressive symptoms ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12117446/

Azetukalner, a Novel KV7 Potassium Channel Opener, in ... These results suggest that azetukalner has the potential to improve symptoms of depression in patients with MDD, with a safety profile ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06922110

An Open-Label Study of Azetukalner in Major Depressive ... X-NOVA-OLE is a multicenter, open-label study to evaluate the long-term safety, tolerability, and efficacy of azetukalner as a monotherapy in adult participants ...

4. investor.xenon-pharma.com investor.xenon-pharma.com/news-releases/news-release-details/xenon-pharmaceuticals-presents-data-phase-2-x-nova-clinical

Xenon Pharmaceuticals Presents Data from Phase 2 X- ... The X-NOVA results demonstrated a clinically meaningful reduction in depression, in addition to an early onset of action, a significant reduction in anhedonia.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40423966/?utm_source=SimplePie&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1pq-4TZ0w1pIimA2HHLJZYTkSjaU335U-aRSFRxJ31Blahz9sN&fc=20220524061305&ff=20250527134028&v=2.18.0.post9+e462414

Azetukalner, a Novel KV7 Potassium Channel Opener, in ... Main outcomes and measures: The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at week 6.

6. aesnet.org aesnet.org/abstractslisting/long-term-safety-and-efficacy-of-azetukalner-a-novel-potent-kv7-potassium-channel-opener-in-adults-with-focal-epilepsy-update-from-the-ongoing-7-year-open-label-extension-of-x-tole

long-term safety and efficacy of azetukalner, a novel, potent ... Azetukalner was generally well tolerated with no new safety signals. These promising interim data continue to suggest long-term safety and efficacy of ...