A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder

NCT06775379 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: XPF-010-D301
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 46

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)

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 (46)

IMA Clinical Research Phoenix

Phoenix, Arizona, 85012, United States

RECRUITING

Woodland International Research Group

Little Rock, Arkansas, 72211, United States

RECRUITING

Woodland Research Northwest

Rogers, Arkansas, 72758, United States

RECRUITING

Behavioral Research Specialists, Llc

Glendale, California, 91206, United States

RECRUITING

Marvel Clinical Research

Huntington Beach, California, 92647, United States

RECRUITING

Irvine Clinical Research

Irvine, California, 92614, United States

RECRUITING

CalNeuro Research Group, Inc.

Los Angeles, California, 90025, United States

RECRUITING

Excell Research Inc.

Oceanside, California, 92056, United States

RECRUITING

Atp Clinical Research

Orange, California, 92866, United States

RECRUITING

Nrc Research Institute

Orange, California, 92868, United States

RECRUITING

CenExel CNS-TO (Collaborative Neuroscience Research)

Torrance, California, 90504, United States

RECRUITING

Sunwise Clinical Research

Walnut Creek, California, 94596, United States

RECRUITING

Ct Clinical Research Associates

Cromwell, Connecticut, 06416, United States

RECRUITING

CNS Clinical Research Group

Coral Springs, Florida, 33067, United States

RECRUITING

NeoClinical Research

Hialeah, Florida, 33016, United States

RECRUITING

Clinical Neuroscience Solutions, Inc.

Jacksonville, Florida, 32256, United States

RECRUITING

Accel Research Sites Lakeland

Lakeland, Florida, 33803, United States

RECRUITING

Accel Research Sites - St. Petersburg-Largo

Largo, Florida, 33777, United States

RECRUITING

PharmaSouth Research

Miami, Florida, 33165, United States

RECRUITING

Quantum Clinical Trials

Miami Beach, Florida, 33140, United States

TERMINATED

Harmony Clinical Research Inc

North Miami Beach, Florida, 33162, United States

RECRUITING

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32801, United States

RECRUITING

Combined Research Orlando Phase I-Iv

Orlando, Florida, 32807, United States

RECRUITING

Panhandle Research and Medical Clinic

Pensacola, Florida, 32503, United States

RECRUITING

Advanced Discovery Research

Atlanta, Georgia, 30318, United States

RECRUITING

Synexus - Atlanta

Atlanta, Georgia, 30328, United States

RECRUITING

CenExel iResearch

Decatur, Georgia, 30030, United States

RECRUITING

Psych Atlanta, Pc

Marietta, Georgia, 30060, United States

RECRUITING

Cenexel Iresearch - Savannah

Savannah, Georgia, 31405, United States

RECRUITING

Northwest Clinical Trials Inc

Boise, Idaho, 83704, United States

RECRUITING

Chicago Research Center Inc.

Chicago, Illinois, 60634, United States

RECRUITING

Boston Clinical Trials Llc

Boston, Massachusetts, 02131, United States

RECRUITING

ELIXIA

Springfield, Massachusetts, 01103, United States

RECRUITING

IMA Clinical Research Las Vegas

Las Vegas, Nevada, 89102, United States

RECRUITING

Redbird Research

Las Vegas, Nevada, 89119, United States

RECRUITING

IMA Clinical Research

Albuquerque, New Mexico, 87109, United States

RECRUITING

Integrative Clinical Trials

Brooklyn, New York, 11229, United States

RECRUITING

Richmond Behavioral Associates

Staten Island, New York, 10314, United States

RECRUITING

New Hope Clinical Research

Charlotte, North Carolina, 28211, United States

RECRUITING

Pahl Pharmaceutical Professionals Llc

Oklahoma City, Oklahoma, 73112, United States

RECRUITING

Lehigh Center For Clinical Research

Allentown, Pennsylvania, 18103, United States

RECRUITING

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

RECRUITING

Delricht Research - Plano

Plano, Texas, 75024, United States

RECRUITING

Aim Trials, Llc

Plano, Texas, 75093, United States

RECRUITING

Grayline Research Center

Wichita Falls, Texas, 76309, United States

RECRUITING

Core Clinical Research

Everett, Washington, 98201, United States

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: January 9, 2025
• First Posted: January 15, 2025
• Study Start: December 20, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (46)