A Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 in Major Depressive Disorder

This is a multicenter, Phase 2, double-blind, randomized, parallel-arm, placebo-controlled clinical trial to evaluate the efficacy, safety, and tolerability of XEN1101 in subjects with Major Depressive Disorder.

Key Inclusion Criteria: * Be properly informed of the nature and risks of the study and given written informed consent. * Male or female, aged 18 through 65 years (inclusive) with a body mass index (BMI) ≤35 kg/m². * Subject must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for current MDD and currently in a moderate to severe major depressive episode (MDE), confirmed using the Mini International Neuropsychiatric Interview (MINI). * Current MDE duration ≥2 months and \1 antidepressant drug due to lack of efficacy in the current MDE. * Failing \>3 antidepressant drug trials, for any reason, in the current MDE. * History of non-response to electroconvulsive therapy (ECT) in the past 10 years. * Active suicidal plan/intent in the past 6 months, or more than 1 lifetime suicide attempt. * Females who are pregnant, breastfeeding, or planning to become pregnant during the first administration of study drug until 3 months after the last dose of study drug. * Meets criteria for a substance use disorder within the past 12 months, with the exception of tobacco use, and/or has a positive urine toxicology screen for drugs of abuse. * Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol.