Azetukalner for Depression

(X-NOVA2 Trial)

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, Substance use, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

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 in helping people with Major Depressive Disorder (MDD) feel better. The study compares azetukalner to a placebo (a pill with no active medicine) to evaluate its effectiveness and safety. Individuals currently experiencing a major depressive episode lasting 6 weeks to 24 months may be suitable candidates, particularly if they do not have other mood disorders or substance use issues. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment for MDD.

Will I have to stop taking my current medications?

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

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

Research shows that azetukalner may help treat major depressive disorder (MDD). Studies indicate it is generally safe and well-tolerated by patients. In research on long-term use, azetukalner remained well-tolerated, with no new safety issues identified.

Azetukalner has also been tested in people with focal epilepsy, and those results confirmed its safety. These studies suggest that azetukalner might be safe for long-term use without unexpected side effects.

Overall, current research supports azetukalner's potential safety for those considering joining a trial for depression treatment. However, as with any treatment, individual experiences may vary, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

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

Most treatments for depression, such as SSRIs and SNRIs, work by altering neurotransmitter levels like serotonin and norepinephrine. But Azetukalner works differently, targeting a novel pathway in the brain that researchers believe could offer faster relief from depressive symptoms. This new mechanism of action sets it apart from existing medications, potentially providing an option for those who haven't responded well to traditional therapies. Researchers are excited because this could mean quicker results and a new hope for individuals with treatment-resistant depression.

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

Research shows that azetukalner, a new treatment under study in this trial, may help reduce symptoms of Major Depressive Disorder (MDD). Studies have found a noticeable decrease in depression symptoms after six weeks of treatment, using a standard measurement tool. Early results also suggest that azetukalner quickly lifts mood and restores interest or pleasure in activities. Additionally, the treatment appears safe and is generally well-tolerated. Overall, these findings suggest that azetukalner could be an effective option for treating depression. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults aged 18-74 with Major Depressive Disorder (MDD) as per DSM-5, currently in a depressive episode lasting 6 weeks to 24 months. Participants must have had their first MDE before age 50 and have a BMI of ≤40 kg/m2. Excluded are those with other mood disorders, recent substance abuse, certain psychiatric conditions like bipolar or schizophrenia, active suicidal intent, non-suicidal self-harm within the past year, pregnancy, or recent antidepressant use.

Inclusion Criteria

Have you felt at least 3 of the following things recently? Feeling sad; low energy or feeling tired; hopelessness or putting yourself down; not being interested in things that you usually enjoy such as hobbies or activities, or friends and family; difficulty concentrating or focusing on things; appetite changes like pushing yourself to eat or overeating; difficulty falling or staying asleep, or oversleeping?

Exclusion Criteria

Have you tried 3 or more antidepressants that haven't worked?

Have you been diagnosed with Bipolar Disorder?

Have you been diagnosed with Obsessive-Compulsive Disorder?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azetukalner 20 mg 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-NOVA2 study is testing Azetukalner against a placebo in adults with MDD. This Phase 3 trial is double-blind and placebo-controlled to ensure neither researchers nor participants know who receives the actual medication versus the placebo for unbiased results.

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 ...