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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified June 2025 by Xenon Pharmaceuticals Inc.
Sponsor
Xenon Pharmaceuticals Inc.
Information Provided by (Responsible Party)
Xenon Pharmaceuticals Inc.
Clinicaltrials.gov Identifier
NCT07076407
Other Study ID Numbers:
XPF-010-D302
First Submitted
July 13, 2025
First Posted
July 21, 2025
Last Update Posted
April 7, 2026
Last Verified
June 2025

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Major Depressive Disorder
Drug: AzetukalnerDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment450 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder
Study Start DateJuly 7, 2025
Actual Primary Completion Date11mos 3w from now
Actual Study Completion Date1yr 1mo from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Azetukalner
Azetukalner 20 mg
Drug: Azetukalner
Azetukalner 20 mg taken orally once a day with food (with the evening meal when possible) for 6 weeks
Placebo
Placebo
Drug: Placebo
Placebo taken orally once a day with food (with the evening meal when possible) for 6 weeks

Outcome Measures

Primary Outcome Measures
  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.
Secondary Outcome Measures
  1. Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) score at 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
    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
    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)

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsXenon Pharmaceuticals Inc.
Locations
Harmonex Neuroscience Research | Dothan Alabama, United States, 36303University of Alabama at Birmingham, Huntsville Regional Medical Campus | Huntsville Alabama, United States, 35801Pillar Clinical Research | Bentonville Arkansas, United States, 72712SanRo Clinical Research Group | Bryant Arkansas, United States, 72022Clinical Innovations Inc | Bellflower California, United States, 90706Center for Neurohealth | La Jolla California, United States, 93037Artemis Institute for Clinical Research | San Diego California, United States, 92103California Neuroscience Research | Sherman Oaks California, United States, 91403Pacific Clinical Research Management Group | Upland California, United States, 91786Institute of Living | Hartford Connecticut, United States, 06106Gulfcoast Clinical Research Center | Fort Myers Florida, United States, 33912Sarkis Clinical Trials | Gainesville Florida, United States, 32607Equipath Health and Research Tampa Bay, Llc | Riverview Florida, United States, 33578Delricht Research | Atlanta Georgia, United States, 30329Emory University Brain Health Center | Atlanta Georgia, United States, 30329Advanced Quality Medical Research | Orland Park Illinois, United States, 60462Smart Trials, LLC | Jefferson Louisiana, United States, 70121Pharmasite Research Inc. | Baltimore Maryland, United States, 21208-6605Adams Clinical Boston | Boston Massachusetts, United States, 02116Activmed Practices & Research, Llc - Methuen | Methuen Massachusetts, United States, 01844Adams Clinical Watertown | Watertown Massachusetts, United States, 02472Vitalix Clinical, Inc | Worcester Massachusetts, United States, 01608Psychiatric Care and Research Center | O'Fallon Missouri, United States, 63368St. Charles Psychiatric Associates - Midwest Research Group | Saint Charles Missouri, United States, 63304Lumina Clinical Research Center | Cherry Hill New Jersey, United States, 08002Princeton Medical Institute | Princeton New Jersey, United States, 08540Bio Behavioral Health | Toms River New Jersey, United States, 08755Bioscience Research, LLC | Mount Kisco New York, United States, 10549Fieve Clinical Research, Inc. | New York New York, United States, 10017IMA Clinical Research | New York New York, United States, 10128Magnolia Clinical Research, Llc | Cary North Carolina, United States, 27511Insight Clinical Trials | Independence Ohio, United States, 44195Sooner Clinical Research | Oklahoma City Oklahoma, United States, 73116Austin Clinical Trial Partners | Austin Texas, United States, 78737Boeson Research | Provo Utah, United States, 84604Suomen Terveystalo Oy | Helsinki , Finland, 00180Oulu Mentalcare Oy | Oulu , Finland, 90100Clinical Medical Research Sp. z o.o. | Katowice , Poland, 40156Praktyka Lekarska Malgorzata Wojtanowska-Bogacka | Poznan , Poland, 60192Specjalistyczna Praktyka Lekarska, Filip Rybakowski | Poznan , Poland, 60744Clinica Nutrimed Cercetare Sr | Bucharest , Romania, 020744Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu Liptovsky Mikulas | Liptovský Mikuláš , Slovakia, 03123