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

Official title

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder

Overview

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)

Interventions

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

Primary outcome measures

• Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6 [Time frame: Baseline to Week 6]

Secondary outcome measures (4)

• Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) score at Week 6 [Time frame: Baseline to Week 6]
• Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 1 [Time frame: Baseline to Week 1]
• Change from baseline in the Clinical Global Impression of Severity (CGI-S) score at Week 6 [Time frame: Baseline to Week 6]
• To assess the safety and tolerability of azetukalner (e.g., adverse events) [Time frame: From screening (approximately 4 weeks prior to baseline) through to 8 weeks post-final dose.]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 35 centers

• Harmonex Neuroscience Research — Dothan
• University of Alabama at Birmingham, Huntsville Regional Medical Campus — Huntsville
• Pillar Clinical Research — Bentonville
• SanRo Clinical Research Group — Bryant
• Clinical Innovations Inc — Bellflower
• Center for Neurohealth — La Jolla
• Artemis Institute for Clinical Research — San Diego
• California Neuroscience Research — Sherman Oaks
• … and 27 more centers

Poland · 4 centers

• In Vivo Sp. z.o.o. — Bydgoszcz
• Clinical Medical Research Sp. z o.o. — Katowice
• Praktyka Lekarska Malgorzata Wojtanowska-Bogacka — Poznan
• Specjalistyczna Praktyka Lekarska, Filip Rybakowski — Poznan

Finland · 2 centers

• Suomen Terveystalo Oy — Helsinki
• Oulu Mentalcare Oy — Oulu

Germany · 2 centers

• Charite - Universitatsmedizin Berline — Berlin
• Boehm-Peters PartGmbB - Praxis fur Psychiatrie, Psychotherapie, Neurologie — Rosenheim

Romania · 2 centers

• Clinica Nutrimed Cercetare Sr — Bucharest
• Institutul Privat De Cercetari Melchisedec (ICPM) Pentru Boli Autoimune Ereditare si Rare — Craiova

Slovakia · 2 centers

• Dana Ignjatovićová, spol. s r.o — Banská Bystrica
• Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu Liptovsky Mikulas — Liptovský Mikuláš

Spain · 1 center

• Hospital Universitari Vall D'Hebron — Barcelona

Identifiers

NCT: NCT07076407 · XPF-010-D302

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗