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

Study Overview
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Brief Summary
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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.

Detailed Description
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The study is divided into 3 stages: Screening - up to 4 weeks duration; Treatment - 6 weeks duration; Follow-up - 4 weeks duration. The total study duration per subject is estimated to be approximately 14 weeks.

Official Title
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A Proof-of-Concept, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 in Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: XEN1101 10 mg
* Drug: XEN1101 20 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 <24 months at the time of screening. Current illness severity that is at least moderate, defined as a score of ≥20 on the HAM-D17 at screening and on Day 1. Score ≥20 on the SHAPS at screening and on Day1. Must be willing to comply with the study protocol for the full term of the study. Key Exclusion Criteria: A primary psychiatric diagnosis other than MDD as defined by DSM-5 (comorbid anxiety disorders [including agoraphobia, generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), and panic disorder] are allowed). Concomitant use of antidepressants and/or other disallowed pharmacotherapy (including benzodiazepines). History of schizophrenia or other psychotic disorder, MDD with psychotic features, bipolar I or II disorder, or MDD with mixed features. History of non-response to >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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XEN1101 10 mg<br>During the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 10 mg, orally with food, per day | Drug: XEN1101 10 mg<br>* XEN1101 oral capsule<br>|
| Experimental: XEN1101 20 mg<br>During the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 20 mg, orally with food, per day | Drug: XEN1101 20 mg<br>* XEN1101 oral capsule<br>|
| Placebo Comparator: placebo<br>During the double blind treatment period (42 days), subjects will take 1 capsule of placebo, orally with food, per day | Drug: Placebo<br>* Placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score. |  | From baseline to end of treatment (Week 6). | 
| Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuations. |  | From randomization to Week 10. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Snaith-Hamilton Pleasure Scale (SHAPS) score. |  | From baseline to end of treatment (Week 6). | 
| Change in Beck Anxiety Inventory (BAI) score. |  | From baseline to end of treatment (Week 6). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Major Depressive Disorder, Potassium channel