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

August 7, 2026 updated by: COMPASS Pathways

A Phase III, Multicentre, Randomised, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, and Tolerability of COMP360 in Participants With Treatment-resistant Depression

Efficacy, Safety, and Tolerability of a single administration of COMP360 in participants with treatment-resistant depression (TRD)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study. The study population will include participants aged ≥18 years with TRD.

Overall, 255 participants will be randomised in a 2:1 ratio to receive COMP360 25 mg or placebo.

The study comprises three parts (A, B, and C) and will last approximately 62 weeks including a three- to ten-week Screening Period.

Part A will include a six-week follow-up from initial investigational product (IP) administration.

In this study, the primary aim is to assess the efficacy and safety of a single dose of COMP360 25 mg versus placebo for reducing symptom severity in TRD, when administered with psychological support. This will be assessed in a 6-week, single-dose, double-blind, placebo-controlled part of the study (Part A). Durability of efficacy and long-term safety, and the efficacy and safety of re-treatment will be assessed in a 20-week single-dose, double-blind re-treatment part (Part B), and a 26-week open-label treatment part (Part C).

Study Type

Interventional

Enrollment (Actual)

258

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tuscon, Arizona, United States, 85724
        • University of Arizona College of Medicine - Tuscon
    • California
      • Culver City, California, United States, 90230
        • Proscience Research Group
      • Garden Grove, California, United States, 92845
        • Collaborative Neuroscience Network, LLC
      • La Jolla, California, United States, 92037
        • Kadima Neuropsychiatry Institute
      • La Jolla, California, United States, 92037
        • University California San Diego
      • Los Angeles, California, United States, 90004
        • California Center for Psychedelic Therapy
      • Los Angeles, California, United States, 90025
        • CalNeuro Research Group, Inc
      • Los Angeles, California, United States, 90064
        • Clarity Clinical Research, LLC
      • Orange, California, United States, 92868
        • ATP Clinical Research, Inc.
      • San Diego, California, United States, 92103
        • Artemis Institute for Clinical Research
      • San Jose, California, United States, 95124
        • Lumos Clinical Research Center
      • Stanford, California, United States, 94305
        • Stanford University
      • Thousand Oaks, California, United States, 93012
        • Asclepes Research Centers
    • Connecticut
      • Norwich, Connecticut, United States, 06360
        • Comprehensive Psychiatric Care
    • Florida
      • Orlando, Florida, United States, 32803
        • Apg Research, Llc
      • Orlando, Florida, United States, 32801
        • Clinical Neurosciecne Solutions, Inc. dba CNS Healthcare
      • Tampa, Florida, United States, 33782
        • DMI Health Care Group, Inc
      • Tampa, Florida, United States, 33803
        • Meridien Research/Accel Research
    • Georgia
      • Atlanta, Georgia, United States, 30060
        • Psych Atlanta
      • Atlanta, Georgia, United States, 30329-2209
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60640
        • Uptown Research Institute, LLC
    • Maryland
      • Baltimore, Maryland, United States, 21044
        • Sheppard Pratt Health System
      • Gaithersburg, Maryland, United States, 20877
        • CBH Health, LLC
      • Pikesville, Maryland, United States, 21208
        • Pharmasite Research, Inc
    • Massachusetts
      • North Worcester, Massachusetts, United States, 01655
        • University of Massachusetts Medical School
    • Minnesota
      • Minneapolis, Minnesota, United States, 55416
        • University of Minnesota
    • Missouri
      • Columbia, Missouri, United States, 65212
        • University of Missouri
      • Saint Charles, Missouri, United States, 63304
        • Midwest Research Group
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nebraska
      • Lincoln, Nebraska, United States, 68526
        • Alivation Research, LLC.
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Bio Behavioral Health
    • New York
      • New York, New York, United States, 10128
        • The Medical Research Network, LLC
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Insight Clinical Trials, LLC
      • North Canton, Ohio, United States, 44720
        • Neuro-Behaviroral Clinical Research, Inc.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Rivus Wellness & Research Institute
    • Pennsylvania
      • Moosic, Pennsylvania, United States, 18507
        • Global Medical Institutes, LLC, Scranton Medical Institute
    • Texas
      • Houston, Texas, United States, 77030
        • UT Health Science Center at Houston (UTHSC-H)
    • Utah
      • Draper, Utah, United States, 84020
        • Cedar Clinical Research
    • Washington
      • Everett, Washington, United States, 98201
        • Core Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. Aged ≥18 years at Screening
  2. Major depression without psychotic features (single or recurrent episode as informed by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-5])
  3. 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
  4. MADRS total score ≥20 at Screening and Baseline to ensure at least moderate severity of depression
  5. 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.
  6. At Screening, agreement to discontinue all prohibited medications.

Key Exclusion Criteria:

Psychiatric Exclusion Criteria:

  1. 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)
  2. Lifetime paranoid, schizoid, schizotypal, histrionic, narcissistic personality disorder, or any ongoing serious psychiatric comorbidity based on medical history and clinical judgement
  3. Borderline personality disorder as demonstrated by medical history or the Mini International Neuropsychiatric Interview Plus (MINI plus) - borderline personality disorder module
  4. 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)
  5. Psychiatric inpatient within the past 12 months prior to Screening
  6. Use of electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation during the current depressive episode
  7. Transcranial magnetic stimulation within the past six months prior to Screening
  8. 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
  9. Exposure to COMP360 psilocybin therapy prior to Screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Matched placebo
Drug: Psilocybin
COMP360 Psilocybin administered under supportive conditions
Other Names:
  • COMP360
Experimental: 25 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
COMP360 25 mg versus placebo for the change from baseline in MADRS total score
Time Frame: Week 6
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 placebo for the change from baseline in SDS total score
Time Frame: Week 6
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

COMPASS Pathways

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2023

Primary Completion (Actual)

May 28, 2025

Study Completion (Actual)

April 15, 2026

Study Registration Dates

First Submitted

November 14, 2022

First Submitted That Met QC Criteria

November 14, 2022

First Posted (Actual)

November 22, 2022

Study Record Updates

Last Update Posted (Actual)

August 10, 2026

Last Update Submitted That Met QC Criteria

August 7, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COMP 005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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