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

NCT05733546 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: COMP 104
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Major Depressive Disorder

Keywords

psilocybin, MDD

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of COMP360 Psilocybin

  Proportion of patients with adverse events (AEs)

  Up to Week 6

Secondary Outcomes (2)

• Pharmacokinetics of COMP360 Psilocybin

  Day 1

• Change from baseline in MADRS total score at Week 3 and Week 6 for COMP360 25 mg versus COMP360 1 mg

  Week 3 and Week 6

Study Arms (3)

25 mg COMP360 Psilocybin

EXPERIMENTAL

25 mg COMP360 Psilocybin

Drug: Psilocybin

10 mg COMP360 Psilocybin

EXPERIMENTAL

10 mg COMP360 Psilocybin

Drug: Psilocybin

1 mg COMP360 Psilocybin

ACTIVE COMPARATOR

1 mg COMP360 Psilocybin

Drug: Psilocybin

Interventions

Psilocybin DRUG

COMP360 Psilocybin administered under supportive conditions

Also known as: COMP360

1 mg COMP360 Psilocybin; 10 mg COMP360 Psilocybin; 25 mg COMP360 Psilocybin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• COMPASS Pathways: lead

Study Sites (5)

Kadima Neuropsychiatry Institute

La Jolla, California, 92037, United States

Location

Clinical Neuroscience Solutions Inc

Jacksonville, Florida, 32256, United States

Location

Sunstone Therapies

Rockville, Maryland, 20850, United States

Location

Elixia MA, LLC

Springfield, Massachusetts, 01103, United States

Location

Aims Trial

Plano, Texas, 75093, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: February 17, 2023
• Study Start: January 30, 2023
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)