A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder

Phase 3

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: Placebo; Drug: Azetukalner

• Registration Number: NCT06775379
• Lead Sponsor: Xenon Pharmaceuticals Inc.

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study Start: 2024-12-20
• Status Verified: 2025-01
• Study First Submitted: 2025-01-09
• Study First Submitted QC: 2025-01-09
• Study First Posted: 2025-01-15
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-25
• Primary Completion: 2026-08
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
Azetukalner	Azetukalner	Azetukalner 20 mg

Primary Outcome Measures

Name	Time	Method
Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6	Baseline to Week 6

Secondary Outcome Measures

Name	Time	Method
Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) score at Week 6	Baseline to Week 6
Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 1	Baseline to Week 1
Change from baseline in the Clinical Global Impression of Severity (CGI-S) score at Week 6	Baseline to Week 6

Trial Locations

Locations (17)

Woodland International Research Group; 🇺🇸 Little Rock, Arkansas, United States

Excell Research Inc.; 🇺🇸 Oceanside, California, United States

Sunwise Clinical Research; 🇺🇸 Walnut Creek, California, United States

NeoClinical Research; 🇺🇸 Hialeah, Florida, United States

Accel Research Sites Lakeland; 🇺🇸 Lakeland, Florida, United States

Quantum Clinical Trials; 🇺🇸 Miami Beach, Florida, United States

PharmaSouth Research; 🇺🇸 Miami, Florida, United States

Panhandle Research and Medical Clinic; 🇺🇸 Pensacola, Florida, United States

CenExel iResearch; 🇺🇸 Decatur, Georgia, United States

Integrative Clinical Trials; 🇺🇸 Brooklyn, New York, United States

Core Clinical Research; 🇺🇸 Everett, Washington, United States

IMA Clinical Research Phoenix; 🇺🇸 Phoenix, Arizona, United States

CenExel CNS-TO (Collaborative Neuroscience Research); 🇺🇸 Torrance, California, United States

Clinical Neuroscience Solutions, Inc.; 🇺🇸 Memphis, Tennessee, United States

Chicago Research Center Inc.; 🇺🇸 Chicago, Illinois, United States

IMA Clinical Research Las Vegas; 🇺🇸 Las Vegas, Nevada, United States

IMA Clinical Research; 🇺🇸 Albuquerque, New Mexico, United States