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NCT Number: NCT06775379

A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder

X-NOVA2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)

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Key information

Conditions

Major Depressive Disorder Behavior Behavioral Symptoms Depression Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–74 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

IMA Clinical Research Phoenix, Phoenix, Arizona, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age
  • Body Mass Index (BMI) ≤40 kg/m2
  • Meets the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) criteria for current major depressive disorder and is currently in an MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI)
  • Participant's current MDE has a duration of ≥6 weeks and ≤24 months.

Key Exclusion Criteria:

  • Participant has a primary diagnosis of a mood disorder other than MDD.
  • Participant has a history of any of the following: MDD with psychotic or catatonic features; MDD with mixed features; Bipolar I or II disorder; Obsessive-compulsive disorder; Schizophrenia, primary thought disorder, or other psychotic disorder.
  • Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum or perimenopausal onset; Post traumatic stress disorder; Antisocial or borderline personality disorder (or presence of clinically significant borderline personality traits); Panic disorder and/or agoraphobia; ADHD treated with a psychostimulant, diagnosed during the current MDE, or with unstable symptoms, as judged by the investigator.
  • Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening.
  • Participant has had an active suicidal plan/intent within the 6 months prior to screening, presence of suicidal behavior in the last 2 years, or >1 suicide attempt >24 years of age.
  • Participant has a history of non-suicidal self-harm behavior in the 12 months prior to screening.
  • Participant has used antidepressants or other prohibited medications (including benzodiazepines), within the 2 weeks (4 weeks for fluoxetine) or within a period less than 5 times the drug's half-life, whichever is longer, prior to randomization.
  • Participant has a history of non-response to ≥2 antidepressant drugs of adequate dose and duration in the current MDE as determined by the Antidepressant Treatment Response Questionnaire (ATRQ).
  • Participants with medical conditions that may interfere with the purpose or conduct of the study
  • Participant is pregnant, breastfeeding, or planning to become pregnant.

Treatment and study plan

Azetukalner

Drug

Azetukalner 20 mg taken orally once a day with food (with the evening meal when possible) for 6 weeks

Other names: XEN1101

Placebo

Drug

Placebo taken orally once a day with food (with the evening meal when possible) for 6 weeks

Primary outcomes

  1. Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6

    Time frame: Baseline to Week 6

    The HAMD-17 consists of 17 items that are used to rate the severity of depression symptoms. Each item is scored in a range of 0 to 2 points or 0 to 4 points, with higher scores indicating a greater degree of depression. The score for each item is summed to compute a total score, which ranges from 0 to 52 points.

Secondary outcomes

  1. Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) score at Week 6

    Time frame: Baseline to Week 6

    The SHAPS is a 14-item self-report questionnaire used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater anhedonia. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are assigned a score of 1, while "strongly disagree" responses are assigned a score of 4 points. Total scores on the SHAPS can range from 14 to 56 points, with higher scores corresponding to higher levels of anhedonia.

  2. Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 1

    Time frame: Baseline to Week 1

    The HAMD-17 consists of 17 items that are used to rate the severity of depression symptoms. Each item is scored in a range of 0 to 2 points or 0 to 4 points, with higher scores indicating a greater degree of depression. The score for each item is summed to compute a total score, which ranges from 0 to 52 points.

  3. Change from baseline in the Clinical Global Impression of Severity (CGI-S) score at Week 6

    Time frame: Baseline to Week 6

    The CGI-S is a clinician-rated global measure of participant overall disease severity. Participants are rated on a 7-point severity scale, with higher scores indicating more severe depression.

  4. To assess the safety and tolerability of azetukalner (e.g., adverse events)

    Time frame: From screening (approximately 4 weeks prior to baseline) through to 8 weeks post-final dose.

Study contacts

Contact information is provided by the study sponsor or research team.

Xenon Medical Affairs

CONTACT

[email protected]

1-604-484-3300

Sponsors and collaborators

Lead sponsor

Xenon Pharmaceuticals Inc.

Industry

Registry information

Official study title

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder

Acronym: X-NOVA2

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jan 15, 2025
Registry last updated
Oct 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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