A Phase II, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of COMP360 in Participants With Major Depressive Disorder With One Prior Treatment Failure

Study Overview
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Brief Summary
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Safety, Tolerability, pharmacokinetics and efficacy of a single administration of COMP360 in participants with Major Depressive Disorder with one prior treatment failure.

Detailed Description
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This is a phase II, multi-centre, randomised, double-blind, controlled study. The study population will include participants aged ≥18 years with Major Depressive Disorder (MDD) with one prior treatment failure of an antidepressant in their current depressive episode. Overall, 102 participants will be randomised in a 2:1 ratio to receive COMP360 25 mg or COMP360 1 mg. In this study the aim is to investigate the safety and tolerability of COMP360, administered with psychological support, in adult participants with MDD with one prior treatment failure. In addition, pharmacokinetics and efficacy of COMP360 will be investigated. The study will last up to 16 weeks including a three- to ten-week Screening Period and a six-week follow-up from investigational product (IP) administration.

Official Title
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A Phase II, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of COMP360 in Participants With Major Depressive Disorder With One Prior Treatment Failure

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Psilocybin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Aged ≥18 years at Screening Major depression without psychotic features (single or recurrent episode as informed by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-5]) If the current major depressive episode is the participant's first lifetime episode of depression, the length of the current episode must be ≥3 months and ≤2 years at Screening MADRS total score ≥20 at Screening and Baseline to ensure at least moderate severity of depression. Failure to respond to an adequate dose and duration of one pharmacological treatment for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and using the supplementary advice on additional antidepressants not included in MGH-ATRQ. At Screening, agreement to discontinue all prohibited medications. Key Exclusion Criteria: Prior or ongoing bipolar disorder, any psychotic disorder, including schizophrenia, schizophreniform disorder, schizoaffective disorder, brief psychotic disorder (unless substance induced or due to a medical condition), antisocial personality disorder as assessed by a structured clinical interview (MINI 7.0.2) Lifetime paranoid, schizoid, schizotypal, histrionic, narcissistic personality disorder, or any ongoing serious psychiatric comorbidity based on medical history and clinical judgement Borderline personality disorder as demonstrated by medical history or the Mini International Neuropsychiatric Interview Plus (MINI plus) - borderline personality disorder module Ongoing post-traumatic stress disorder, obsessive-compulsive disorder, or anorexia nervosa as assessed by medical history and a structured clinical interview (MINI 7.0.2) Psychiatric inpatient within the past 12 months prior to Screening Use of electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation during the current depressive episode Transcranial magnetic stimulation within the past six months prior to Screening Current enrolment in a psychological therapy programme that will not remain stable for the duration of the study. Psychological therapies cannot have been initiated within 30 days prior to Screening Exposure to COMP360 psilocybin therapy prior to Screening

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg COMP360 Psilocybin<br>25 mg COMP360 Psilocybin | Drug: Psilocybin<br>* COMP360 Psilocybin administered under supportive conditions<br>* Other names: COMP360;|
| Active Comparator: 1 mg COMP360 Psilocybin<br>1 mg COMP360 Psilocybin | Drug: Psilocybin<br>* COMP360 Psilocybin administered under supportive conditions<br>* Other names: COMP360;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of COMP360 Psilocybin | Proportion of patients with adverse events (AEs) | Up to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of COMP360 Psilocybin | Plasma concentrations of psilocybin, psilocin, 4-hydroxyindoleacetic acid (4-HIAA) and psilocin-O-glucuronide post-COMP360 administration on Day 1 | Day 1 | 
| Change from baseline in MADRS total score at Week 3 and Week 6 for COMP360 25 mg versus COMP360 1 mg | Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician rated scale measuring depression severity | Week 3 and Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psilocybin, MDD