A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA3)

NCT07076407 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: XPF-010-D302
• Study Type: interventional
• Target: 450
• Locations: 5 countries
• Sites: 42

Brief Summary

X-NOVA3 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)

Conditions

Major Depressive Disorder

Keywords

Depression; Antidepressant; XEN1101; Azetukalner

Outcome Measures

Primary Outcomes (1)

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

  Baseline to Week 6

Secondary Outcomes (4)

• 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

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

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

Study Arms (2)

Azetukalner

EXPERIMENTAL

Azetukalner 20 mg

Drug: Azetukalner

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Azetukalner DRUG

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

Also known as: XEN1101

Azetukalner

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xenon Pharmaceuticals Inc.: lead

Study Sites (42)

Harmonex Neuroscience Research

Dothan, Alabama, 36303, United States

RECRUITING

University of Alabama at Birmingham, Huntsville Regional Medical Campus

Huntsville, Alabama, 35801, United States

RECRUITING

Pillar Clinical Research

Bentonville, Arkansas, 72712, United States

RECRUITING

SanRo Clinical Research Group

Bryant, Arkansas, 72022, United States

RECRUITING

Clinical Innovations Inc

Bellflower, California, 90706, United States

RECRUITING

Center for Neurohealth

La Jolla, California, 93037, United States

RECRUITING

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

RECRUITING

California Neuroscience Research

Sherman Oaks, California, 91403, United States

RECRUITING

Pacific Clinical Research Management Group

Upland, California, 91786, United States

RECRUITING

Institute of Living

Hartford, Connecticut, 06106, United States

RECRUITING

Gulfcoast Clinical Research Center

Fort Myers, Florida, 33912, United States

RECRUITING

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

RECRUITING

Equipath Health and Research Tampa Bay, Llc

Riverview, Florida, 33578, United States

RECRUITING

Delricht Research

Atlanta, Georgia, 30329, United States

RECRUITING

Emory University Brain Health Center

Atlanta, Georgia, 30329, United States

RECRUITING

Advanced Quality Medical Research

Orland Park, Illinois, 60462, United States

RECRUITING

Smart Trials, LLC

Jefferson, Louisiana, 70121, United States

RECRUITING

Pharmasite Research Inc.

Baltimore, Maryland, 21208-6605, United States

RECRUITING

Adams Clinical Boston

Boston, Massachusetts, 02116, United States

RECRUITING

Activmed Practices & Research, Llc - Methuen

Methuen, Massachusetts, 01844, United States

RECRUITING

Adams Clinical Watertown

Watertown, Massachusetts, 02472, United States

RECRUITING

Vitalix Clinical, Inc

Worcester, Massachusetts, 01608, United States

RECRUITING

Psychiatric Care and Research Center

O'Fallon, Missouri, 63368, United States

RECRUITING

St. Charles Psychiatric Associates - Midwest Research Group

Saint Charles, Missouri, 63304, United States

RECRUITING

Lumina Clinical Research Center

Cherry Hill, New Jersey, 08002, United States

RECRUITING

Princeton Medical Institute

Princeton, New Jersey, 08540, United States

RECRUITING

Bio Behavioral Health

Toms River, New Jersey, 08755, United States

RECRUITING

Bioscience Research, LLC

Mount Kisco, New York, 10549, United States

RECRUITING

Fieve Clinical Research, Inc.

New York, New York, 10017, United States

RECRUITING

IMA Clinical Research

New York, New York, 10128, United States

RECRUITING

Magnolia Clinical Research, Llc

Cary, North Carolina, 27511, United States

RECRUITING

Insight Clinical Trials

Independence, Ohio, 44195, United States

RECRUITING

Sooner Clinical Research

Oklahoma City, Oklahoma, 73116, United States

RECRUITING

Austin Clinical Trial Partners

Austin, Texas, 78737, United States

RECRUITING

Boeson Research

Provo, Utah, 84604, United States

RECRUITING

Suomen Terveystalo Oy

Helsinki, 00180, Finland

RECRUITING

Oulu Mentalcare Oy

Oulu, 90100, Finland

RECRUITING

Clinical Medical Research Sp. z o.o.

Katowice, 40156, Poland

RECRUITING

Praktyka Lekarska Malgorzata Wojtanowska-Bogacka

Poznan, 60192, Poland

RECRUITING

Specjalistyczna Praktyka Lekarska, Filip Rybakowski

Poznan, 60744, Poland

RECRUITING

Clinica Nutrimed Cercetare Sr

Bucharest, 020744, Romania

RECRUITING

Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu Liptovsky Mikulas

Liptovský Mikuláš, 03123, Slovakia

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

XEN1101

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Central Study Contacts

Xenon Medical Affairs

CONTACT

1-604-484-3300; XenonCares@xenon-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: July 22, 2025
• Study Start: July 8, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 8, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FI (2); RO (1); SL (1); PL (3); US (35)