A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA2)

Xenon Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Major Depressive Disorder

Treatments: Drug: Placebo; Drug: Azetukalner

Study type: Interventional

Funder types: Industry

Identifiers

NCT06775379

XPF-010-D301

Details and patient eligibility

About

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)

Enrollment: 450 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 onset; Posttraumatic 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 ≥2 lifetime suicide attempts.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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450 participants in 2 patient groups, including a placebo group

Azetukalner

Experimental group

Description:

Azetukalner 20 mg

Treatment:

Drug: Azetukalner

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo