Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRD

Study Overview
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Brief Summary
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Efficacy, Safety, and Tolerability of two administrations of COMP360 in participants with treatment-resistant depression (TRD)

Detailed Description
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This is a phase III, international, multi-centre, randomised, parallel group, fixed repeat dose, double-blind, controlled study. The study population will include participants aged ≥18 years with TRD. Overall, 568 participants are to be randomised in a 2:1:1 ratio to receive COMP360 25 mg, 10 mg or 1 mg. The study will last up to 16 weeks including a three- to ten-week Screening Period and six-week follow-up from investigational product (IP) administration. In this study, the aim is to assess the efficacy of COMP360, administered with psychological support in adult participants with TRD, in improving symptoms of depression.

Official Title
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A Phase III, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With Treatment-resistant Depression

Conditions
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Treatment Resistant Depression

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 TRD, defined as failure to respond to an adequate dose and duration of two, three, or four different pharmacological treatments 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;|
| Experimental: 10 mg COMP360 Psilocybin<br>10 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, active comparator | 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 |
| --- | --- | --- |
| COMP360 25 mg versus COMP360 1 mg for the change from baseline in MADRS total score. | Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician rated scale measuring depression severity | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COMP360 25 mg versus COMP360 1 mg for the change from baseline in Sheehan Disability Scale (SDS) total score. | Sheehan Disability Scale (SDS) is a brief, five-item self report inventory that assesses functional impairment in work/school, social life, and family life. | Week 6 | 
| COMP360 25 mg versus COMP360 10 mg for the change from baseline in MADRS total score. | Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician rated scale measuring depression severity | Week 6 | 
| COMP360 25 mg versus COMP360 10 mg for the change from baseline in Sheehan Disability Scale (SDS) total score. | Sheehan Disability Scale (SDS) is a brief, five-item self report inventory that assesses functional impairment in work/school, social life, and family life. | Week 6 | 

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