Treatment Resistant DepressionPhase 3NCT05624268
Efficacy, Safety, and Tolerability of COMP360 in Participants With TRD
A Phase 3 study testing Psilocybin in people with Treatment Resistant Depression, run by COMPASS Pathways at 40 sites in United States.
Trial summary
Efficacy, Safety, and Tolerability of a single administration of COMP360 in participants with treatment-resistant depression (TRD) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Psilocybin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 258 participants
- Where
- 40 sitesUnited States
- Study dates
- 24 Jan 2023to 15 Apr 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Psychiatric 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
Show all 10Show fewer
- 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
Trial locations and contacts
40 sites in 1 country.
40 sites in 1 country
United States40 sites
Psych Atlanta
Atlanta, Georgia, 30060
Emory University
Atlanta, Georgia, 30329-2209
Sheppard Pratt Health System
Baltimore, Maryland, 21044
Insight Clinical Trials, LLC
Beachwood, Ohio, 44122
Uptown Research Institute, LLC
Chicago, Illinois, 60640
University of Missouri
Columbia, Missouri, 65212
ProScience Research Group
Culver City, California, 90230
Cedar Clinical Research
Draper, Utah, 84020
Core Clinical Research
Everett, Washington, 98201
CBH Health, LLC
Gaithersburg, Maryland, 20877
Collaborative Neuroscience Network, LLC
Garden Grove, California, 92845
UT Health Science Center at Houston (UTHSC-H)
Houston, Texas, 77030
Kadima Neuropsychiatry Institute
La Jolla, California, 92037
University California San Diego
La Jolla, California, 92037
Alivation Research, LLC.
Lincoln, Nebraska, 68526
California Center for Psychedelic Therapy
Los Angeles, California, 90004
CalNeuro Research Group, Inc
Los Angeles, California, 90025
Clarity Clinical Research, LLC
Los Angeles, California, 90064
University of Minnesota
Minneapolis, Minnesota, 55416
Global Medical Institutes, LLC, Scranton Medical Institute
Moosic, Pennsylvania, 18507
New York State Psychiatric Institute
New York, New York, 10032
The Medical Research Network, LLC
New York, New York, 10128
Neuro-Behaviroral Clinical Research, Inc.
North Canton, Ohio, 44720
University of Massachusetts Medical School
North Worcester, Massachusetts, 01655
Comprehensive Psychiatric Care
Norwich, Connecticut, 06360
Rivus Wellness & Research Institute
Oklahoma City, Oklahoma, 73112
ATP Clinical Research, Inc.
Orange, California, 92868
Clinical Neurosciecne Solutions, Inc. dba CNS Healthcare
Orlando, Florida, 32801
APG Research, LLC
Orlando, Florida, 32803
Pharmasite Research, Inc
Pikesville, Maryland, 21208
Midwest Research Group
Saint Charles, Missouri, 63304
Artemis Institute for Clinical Research
San Diego, California, 92103
Lumos Clinical Research Center
San Jose, California, 95124
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
DMI Health Care Group, Inc
Tampa, Florida, 33782
Meridien Research/Accel Research
Tampa, Florida, 33803
ASCLEPES Research Centers
Thousand Oaks, California, 93012
Bio Behavioral Health
Toms River, New Jersey, 08755
University of Arizona College of Medicine - Tuscon
Tuscon, Arizona, 85724
About this study
Official title: 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)
Read the 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).
- Conditions
- Treatment Resistant Depression
- Being tested
- Psilocybin
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Also called COMP360
COMP360 Psilocybin administered under supportive conditions
| Study group | Role | What they receive |
|---|---|---|
| 25 mg COMP360 Psilocybin | Experimental | 25 mg COMP360 Psilocybin Receives: Drug: Psilocybin |
| Placebo | Placebo comparator | Matched placebo Receives: Drug: Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
COMP360 25 mg versus placebo 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
Measured: Week 6
Secondary outcomes (1)
COMP360 25 mg versus placebo for the change from baseline in 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.
Measured: Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2022
- Study start24 Jan 2023
- Primary completion28 May 2025
- Study completion15 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 258 participants (actual)
Sponsor and investigators
- Lead sponsor
- COMPASS Pathways
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05624268
- Sponsor's protocol ID
- COMP 005
- Status last verified
- Aug 2026
- First submitted
- 14 Nov 2022
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05624268
- Acronym / sponsor ID
- COMP 005
- Conditions
- Treatment Resistant Depression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 258 participants (actual)
- Lead sponsor
- COMPASS PathwaysIndustry (pharma, biotech, devices)
- Study start
- 24 Jan 2023 (actual)
- Primary completion
- 28 May 2025 (actual)
- Study completion
- 15 Apr 2026 (actual)
- First posted
- 22 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efficacy, Safety, and Tolerability of a single administration of COMP360 in participants with treatment-resistant depression (TRD)
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 25 mg COMP360 Psilocybin | Experimental | Drug: Psilocybin25 mg COMP360 Psilocybin |
| Placebo | Placebo comparator | Drug: PsilocybinMatched placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PsilocybinAlso: COMP360COMP360 Psilocybin administered under supportive conditions | Drug | 25 mg COMP360 Psilocybin, Placebo |
Primary outcome
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
1 secondary outcome
COMP360 25 mg versus placebo for the change from baseline in SDS total score
Time frame: Week 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
40 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Psilocybin in people with Treatment Resistant Depression, run by COMPASS Pathways at 40 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
COMP360 25 mg versus placebo for the change from baseline in MADRS total score (time frame: Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.