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

Safety, Tolerability, pharmacokinetics and efficacy of a single administration of COMP360 in participants with recurrent Major Depressive Disorder.

Study Overview

• Status: Active, not recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Psilocybin

Detailed Description

This is a phase II, multi-centre, randomised, double-blind, controlled study. The study population will include participants aged ≥18 years with recurrent Major Depressive Disorder (MDD) with up to four prior treatment failures of an antidepressant in their current depressive episode.

Overall, 102 participants will be randomised in a 1:1:1 ratio to receive COMP360 25 mg, COMP360 10mg 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.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Kadima Neuropsychiatry Institute
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions Inc
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Sunstone Therapies
  • Massachusetts
    • Springfield, Massachusetts, United States, 01103
      • Elixia MA, LLC
  • Texas
    • Plano, Texas, United States, 75093
      • Aims Trial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 up to four 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 25 mg COMP360 Psilocybin	Drug: Psilocybin; COMP360 Psilocybin administered under supportive conditions; Other Names: COMP360
Active Comparator: 1 mg COMP360 Psilocybin	Drug: Psilocybin; COMP360 Psilocybin administered under supportive conditions; Other Names: COMP360
Experimental: 10 mg COMP360 Psilocybin	Drug: Psilocybin; COMP360 Psilocybin administered under supportive conditions; Other Names: COMP360

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: COMPASS Pathways

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 14, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: psilocybin, MDD
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: COMP 104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No