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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Drug: Psilocybin

Detailed Description

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 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 nine-week follow-up from initial investigational product (IP) administration.

Part B will include a further 17 weeks follow-up out to 26 weeks from initial IP administration.

Part C will include a further 26 weeks follow-up out to 52 weeks from initial 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.

• Study Type: Interventional
• Enrollment (Actual): 572
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Vancouver, Canada
    • Centre for Neurology Studies
  • Vancouver, Canada
    • Medical Arts Research Group
  • B.C.
    • Québec, B.C., Canada, J1L 0H8
      • DIEX Recherche Sherbrooke Inc.
  • British Columbia
    • Kamloops, British Columbia, Canada
      • Medical Arts Health Research Centre, Kamloops
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Okanagan Clinical Trials
    • Penticton, British Columbia, Canada, V2A 5L5
      • Medical Arts Research Group - Penticton
  • Ontario
    • Chatham, Ontario, Canada
      • Chatham-Kent Clnical Trials Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada
      • Centre for Addiction and Mental Health (CAMH)
• Czechia
  • Klecany, Czechia, 25067
    • National Institute of Mental Health
  • Kutná Hora, Czechia, 28401
    • Neuroterapie KH Sro
  • Ostrava, Czechia, 70868
    • Psychiatric Ambulance
  • Pilsen, Czechia, 30100
    • A-SHINE s.r.o.
  • Prague, Czechia, 18600
    • Institut neuropsychiatricke pece
  • Prague, Czechia, 16300
    • Psychedelicka klinika, s.r.o.
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital-Psykiatrien Region Nordjylland
• France
  • Nîmes, France, 30000
    • Centre Hospitalier Universitaire de Nimes (CHU) - Hopital Universitaire Caremeau
  • Paris, France, 75013
    • Universite Paris VI Pierre et Marie Curie - Hopital de La Salpetriere - Centre Emotion - USR 3246 (CNRS UMR 7593)
  • Paris, France, 75014
    • Centre Hospitalier Sainte Anne - Clinique des Maladies Mentales et de l'Encephale (CMME)
  • Paris, France, 75014
    • Ghu-Centre Hospitalier Sainte Anne, Centre de Recherche Clinique
• Germany
  • Berlin, Germany, 12203
    • Charite-Universitaetsmedizin Berlin
  • Frankfurt, Germany, 60528
    • Johann Wolfgang Goethe-Universitaet Frankfurt am Main - Klinik fuer Psychiatrie, Psychosomatik und Psychotherapie
  • Lübeck, Germany, 23562
    • ZiP Campus Luebeck
• Ireland
  • Dublin, Ireland, D24 NR0A
    • Tallaght University Hospital
  • Galway, Ireland, H91 VE03
    • La Nua Day Hospital Mental Health Centre
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Leiden, Netherlands, 2300
    • Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center) - Leiden Institute for Brain and Cognition (LIBC)
  • Utrecht, Netherlands, 3584 CG
    • Universitair Medisch Centrum Utrecht (UMC Utrecht)
• Poland
  • Bydgoszcz, Poland, 85-133
    • Promente - Ośrodek Badań Klinicznych
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House Sp. z o.o.
  • Gdansk, Poland, 80-214
    • Uniwersyteckle Centrum Kliniczne, Klinika Psychiatrii Doroslych
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08830
    • Parc Sanitari Sant Joan de Deu (Sant Joan de Deu Serveis de Salut Mental)
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Sant Boi de Llobregat, Spain, 08830
    • FIDMAG Hermanas Hospitalarias
  • Valladolid, Spain, 47012
    • Hospital Universitario Río Hortega de Valladolid
  • Zamora, Spain, 49021
    • Hospital Provincial de Zamora - Servicio de Psiquiatria
• Sweden
  • Landskrona, Sweden, 26153
    • Vuxenpsykiatrimottagningen
  • Lund, Sweden, 22185
    • Lunds Universitet - Medicinska Fakulteten (Lund University Faculty of Medicine)
  • Solna, Sweden, 17164
    • ClinSmart Sweden AB
  • Stockholm, Sweden, 11239
    • Hälsoklustret
• United Kingdom
  • Chertsey, United Kingdom, KT16 9AU
    • Abraham Cowley Unit - Surrey and Borders Partnership NHS Foundation Trust
  • Chester, United Kingdom, CH2 1HX
    • St. Pancras Clinical Research
  • Doncaster, United Kingdom, DN4 8QN
    • Grounded Research Hub - Rotherham Doncaster & South Humber NHS Foundation Trust
  • Exeter, United Kingdom, EX2 5DW
    • Clinical Research Facility, Royal Devon and Exeter Hospital
  • Fulbourn, United Kingdom, CB21 5EF
    • Fulbourn Hospital - Cambridgeshire And Peterborough NHS Foundation Trust
  • London, United Kingdom, EC2Y 8EA
    • St. Pancras Clinical Research
  • London, United Kingdom, W1G 8DR
    • Clerkenwell Health
  • London, United Kingdom, SE5 8AF
    • King's College London - Institute of Psychiatry, Psychology
  • Newcastle, United Kingdom, NE4 5PL
    • Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust - Wolfson Research Centre
  • Nottingham, United Kingdom, NG7 2TU
    • University Of Nottingham/Nottinghamshire Healthcare Trust, Institute Of Mental Health
  • Oxford, United Kingdom, OX3 7JX
    • The Warneford Hospital- NIHR Clinical Research Facility
  • Sheffield, United Kingdom, S10 3TH
    • Sheffield Health and Social care NHS Foundation Trust
  • Cornwall
    • Bodmin, Cornwall, United Kingdom, PL31 2QT
      • Cornwall Partnership NHS Foundation Trust
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Lighthouse Psychiatry Scottsdale
  • California
    • Bellflower, California, United States, 90706
      • Clinical Innovations, Inc.
    • Encino, California, United States, 91316
      • M3 Wake Research
    • La Jolla, California, United States, 92037
      • Kadima Neuropsychiatry Institute
    • La Jolla, California, United States, 92037-1337
      • The Regents of the University of California - San Diego
    • Los Angeles, California, United States, 90025
      • CalNeuro Research Group, Inc
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Oakland, California, United States, 94610
      • Piedmont Hospital Neuroscience Centre
    • Orange, California, United States, 92868
      • ATP Clinical Research, Inc.
    • Riverside, California, United States, 92506
      • CiTrials
    • San Jose, California, United States, 95124
      • Lumos Clinical Research Center
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Stanford, California, United States, 94305
      • Stanford University
    • Thousand Oaks, California, United States, 93012
      • Asclepes Research Centers
    • Upland, California, United States, 91786
      • Pacific Clinical Research Management Group, LLC
  • Florida
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research, Inc.
    • Miami, Florida, United States, 33125
      • Central Miami Medical Institute, LLC
    • Miami Lakes, Florida, United States, 33016
      • Behavioral Clinical Research, Inc.
    • Okeechobee, Florida, United States, 34972
      • Health Synergy Clinical Research
    • Orlando, Florida, United States, 32801
      • Clinical Neurosciecne Solutions, Inc. dba CNS Healthcare
    • Orlando, Florida, United States, 32803
      • APG Research, LLC- Advanced Psychiatric Group
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
    • Tampa, Florida, United States, 33613-4788
      • University South Florida
    • West Palm Beach, Florida, United States, 33407
      • Health Synergy Clinical Research, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute, LLC
    • Chicago, Illinois, United States, 60612-3227
      • Rush University Medical Center
    • Skokie, Illinois, United States, 60076
      • Psychiatric Medicine Associates
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478-1064
      • Harvard Medical School - McLean Hospital
    • Boston, Massachusetts, United States, 02116
      • Adams Clinical - Boston (Copley Clinical)
    • North Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical - Boston
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Michigan Clinical Research Institute PC
    • Ann Arbor, Michigan, United States, 48109-2700
      • University Of Michigan Comprehensive Depression Center
  • Minnesota
    • Eden Prairie, Minnesota, United States, 55347
      • Institute for Integrative Therapies
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • St. Charles Psychiatric Associates - Midwest Research Group
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Alivation Research, LLC.
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Amherst, New York, United States, 14226-1727
      • Dent Neurosciences Research Center, Inc.
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute
    • New York, New York, United States, 10017
      • Fieve Clinical Research, Inc
    • New York, New York, United States, 10021-4157
      • Spectrum Neuroscience and Treatment Institute
    • New York, New York, United States, 10029
      • Adams Clinical - New York
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
    • The Bronx, New York, United States, 10461
      • Adams Clinical - New York
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati, Department of Psychiatry & Behavirol Neuroscience
    • Cleveland, Ohio, United States, 44113-3108
      • Cleveland Clinic - Lutheran Hospital
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • Texas
    • Austin, Texas, United States, 78712
      • The University of Texas at Austin - Dell Medical School
    • Bellaire, Texas, United States, 77401
      • Houston Clinical Trials, LLC
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials
    • Dallas, Texas, United States, 75247-9119
      • Center for Depression Research and Clinical Care
    • Fort Worth, Texas, United States, 76104
      • North Texas Clinical Trials
    • Houston, Texas, United States, 77046-2401
      • Brain Health Consultants and TMS Center
    • Plano, Texas, United States, 75251
      • HCA Healthcare Research Institute - Medical City Green Oaks Hospital
  • Utah
    • Draper, Utah, United States, 84020
      • Cedar Clinical Research
    • Salt Lake City, Utah, United States, 84108
      • The University of Utah - Huntsman Mental Health Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • Seattle Neuropsychiatric Treatment Center

Participation Criteria

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:

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

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
Experimental: 10 mg COMP360 Psilocybin	Drug: Psilocybin; COMP360 Psilocybin administered under supportive conditions; Other Names: COMP360
Active Comparator: 1 mg COMP360 Psilocybin; 1 mg COMP360 Psilocybin, active comparator	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 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

Collaborators and Investigators

• Sponsor: COMPASS Pathways

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 25, 2023
• First Submitted That Met QC Criteria: January 25, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: psilocybin
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: COMP 006

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