Major Depressive DisorderPhase 2NCT05733546
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
A Phase 2 study testing Psilocybin in people with Major Depressive Disorder, run by COMPASS Pathways at 5 sites in United States.
Trial summary
Safety, Tolerability, pharmacokinetics and efficacy of a single administration of COMP360 in participants with recurrent Major Depressive Disorder. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Psilocybin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 5 sitesUnited States
- Study dates
- 30 Jan 2023to Sep 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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.
- 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.
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Clinical Neuroscience Solutions Inc
Jacksonville, Florida, 32256
Kadima Neuropsychiatry Institute
La Jolla, California, 92037
Aims Trial
Plano, Texas, 75093
Sunstone Therapies
Rockville, Maryland, 20850
Elixia MA, LLC
Springfield, Massachusetts, 01103
About this study
Safety, Tolerability, pharmacokinetics and efficacy of a single administration of COMP360 in participants with recurrent Major Depressive Disorder.
Read the 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.
- Conditions
- Major Depressive Disorder
- Being tested
- Psilocybin
- Keywords
- psilocybin, MDD
- Medical subject headings
- Depressive Disorder, Major
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 |
| 10 mg COMP360 Psilocybin | Experimental | 10 mg COMP360 Psilocybin Receives: Drug: Psilocybin |
| 1 mg COMP360 Psilocybin | Active comparator | 1 mg COMP360 Psilocybin Receives: Drug: Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of COMP360 Psilocybin
Proportion of patients with adverse events (AEs)
Measured: Up to Week 6
Secondary outcomes (2)
Pharmacokinetics of COMP360 Psilocybin
Plasma concentrations of psilocybin, psilocin, 4-hydroxyindoleacetic acid (4-HIAA) and psilocin-O-glucuronide post-COMP360 administration on Day 1
Measured: 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
Measured: Week 3 and Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study start30 Jan 2023
- Primary completionSep 2025 (estimated)
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 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
- NCT05733546
- Sponsor's protocol ID
- COMP 104
- Status last verified
- Aug 2025
- First submitted
- 8 Feb 2023
- Last updated
- 19 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hagel JM, Chang L, Li J, Chen X, Yu L, Gallant JA, Facchini PJ. Bioproduction of a Large-Scale Library of Tryptamine Derivatives for Neuropsychiatric Drug Screening. ACS Chem Biol. 2025 Jun 20;20(6):1212-1231. doi: 10.1021/acschembio.4c00857. Epub 2025 May 15.
PubMed 40375477
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05733546
- Acronym / sponsor ID
- COMP 104
- Conditions
- Major Depressive Disorder
- Keywords
- psilocybin, MDD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 102 participants (actual)
- Lead sponsor
- COMPASS PathwaysIndustry (pharma, biotech, devices)
- Study start
- 30 Jan 2023 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 17 Feb 2023 (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.
Safety, Tolerability, pharmacokinetics and efficacy of a single administration of COMP360 in participants with recurrent Major Depressive Disorder.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 25 mg COMP360 Psilocybin | Experimental | Drug: Psilocybin25 mg COMP360 Psilocybin |
| 10 mg COMP360 Psilocybin | Experimental | Drug: Psilocybin10 mg COMP360 Psilocybin |
| 1 mg COMP360 Psilocybin | Active comparator | Drug: Psilocybin1 mg COMP360 Psilocybin |
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.
- 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.
Key exclusion criteria (8 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
- Use of electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation during the current depressive episode
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 | 1 mg COMP360 Psilocybin, 10 mg COMP360 Psilocybin, 25 mg COMP360 Psilocybin |
Primary outcome
Safety and tolerability of COMP360 Psilocybin
Time frame: Up to Week 6
Proportion of patients with adverse events (AEs)
2 secondary outcomes
Pharmacokinetics of COMP360 Psilocybin
Time frame: Day 1
Change from baseline in MADRS total score at Week 3 and Week 6 for COMP360 25 mg versus COMP360 1 mg
Time frame: Week 3 and Week 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2025.
- Derived from this study: PubMed 40375477Hagel JM, Chang L, Li J, Chen X, Yu L, Gallant JA, Facchini PJ. Bioproduction of a Large-Scale Library of Tryptamine Derivatives for Neuropsychiatric Drug Screening. ACS Chem Biol. 2025 Jun 20;20(6):1212-1231. doi: 10.1021/acschembio.4c00857. Epub 2025 May 15.
- Individual participant dataSharing planned: No
Related trials for Major Depressive Disorder
Enrolling by invitationObservational study
Digital Phenotypes for Predicting Depression_Validation
Major Depressive Disorder, Bipolar I Disorder
Recruiting
Understanding the Neural Underpinnings of Risk-Taking Behavior in Psychiatric Disease
Depression - Major Depressive Disorder
RecruitingPhase 2
Cognitive Dysfunction and Inflammation in Depression: Experimental Inhibition Via Infliximab
Depressive Disorder, Major, Inflammation
RecruitingObservational study
Tracking Response to Antidepressants in Advance of Investigational Trials
Major Depressive Disorder
Not yet recruiting
Sedation and Guided Education for Depression Study
Major Depressive Disorder (MDD)
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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin in people with Major Depressive Disorder, run by COMPASS Pathways at 5 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 8 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: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Safety and tolerability of COMP360 Psilocybin (time frame: Up to Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05733546, which also lists 1 linked publication.
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 19 Aug 2025.