A Phase III, multicentre, randomised, double-blind, controlled study to investigate the efficacy, safety, and tolerability of two initial administrations of COMP360 in participants with treatment-resistant depression
Recipient organisationNIHR Wellcome Trust Cambridge Clinical Research Facility
NIHR supportRecorded as supported by this research centre
PeriodFeb 2025 — Ongoing
In plain English
AI plain-English summary
A single 25 mg dose of a synthetic psilocybin formulation called COMP360 reduced depression scores by 6.6 points on the Montgomery-Åsberg Depression Rating Scale within three weeks in people with treatment-resistant depression, with effects appearing the day after administration. This matters because roughly one-third of people with major depression do not respond to existing antidepressants, leaving them with few options. The phase IIb trial in 233 participants showed that the 25 mg dose produced a rapid, clinically meaningful antidepressant effect that lasted up to six weeks after a single administration, while a 10 mg dose did not show statistically significant improvement. The drug was generally well tolerated. If this phase III trial confirms the results, COMP360 could become a fast-acting treatment for patients who have exhausted standard therapies. Unlike daily pills that take weeks to work, a single or double dose of psilocybin with psychological support could offer a fundamentally different approach to managing treatment-resistant depression, potentially reducing the burden on mental health services and improving quality of life for a hard-to-treat patient group.
View original technical description
A phase IIb, international, multicentre, randomised, double-blind, controlled, dose-finding study (COMP 001) to assess the safety and efficacy of two different single doses of COMP360 (COMPASS Pathfinder Limited’s [COMPASS] proprietary synthetic psilocybin formulation) delivered as monotherapy with psychological support 25 mg and 10 mg versus COMP360 1 mg was conducted in 233 participants with treatment-resistant depression (TRD). For the primary efficacy endpoint, the COMP360 25 mg treatment group versus the COMP360 1 mg treatment group showed a statistically and clinically significant treatment difference of -6.6 points in the change from baseline at Week 3 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score (p<0.001). This treatment difference was apparent from the day after the COMP360 administration session up to Week 6, denoting a rapid antidepressant effect after a single administration. Improvements in the COMP360 10 mg treatment group compared to the COMP360 1 mg treatment group were not statistically significant in the change from baseline at Week 3 in MADRS total score. COMP360 was found to be generally well tolerated, and the secondary and exploratory endpoints supported the primary endpoint findings. In this study, the aim is to assess the efficacy after one and two administrations of COMP360 25 mg or COMP360 10 mg versus COMP360 1 mg for reducing symptom severity in TRD, when administered with psychological support.
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