A Phase III study to investigate two initial administrations of COMP360 in treatment-resistant depression

Prior treatment

• Prior or ongoing bipolar disorder, any psychotic disorder, or antisocial personality disorder
• Psychiatric inpatient within the past six months prior to Screening
• Use of all non invasive somatic treatments within the past six months prior to Screening
• Current enrolment in a psychological therapy programme that will not remain stable
• Alcohol or substance use disorder within the 12 months prior to Screening
• Depression secondary to a medical or drug-related cause in the opinion of the Investigator
• Positive urine drug screens for illicit drugs or drugs of abuse at Screening will be reviewed with participants to determine the pattern of use

Other illness

• Lifetime paranoid, schizoid, schizotypal, histrionic, narcissistic personality disorder, or any ongoing serious psychiatric comorbidity
• Borderline personality disorder
• Ongoing post-traumatic stress disorder, obsessive-compulsive disorder, or anorexia nervosa
• Cardiovascular conditions
• Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus
• Unstable existing thyroid disease/disorder

Lab values

• Clinically significant results on vital signs, ECG, or physical examination at Screening or Baseline, or laboratory tests at Screening

Other

• Please refer to the Protocol for the full list of exclusion criteria
• Use of all invasive somatic treatments during the current depressive episode
• Exhibiting significant suicide risk
• Lifetime exposure to psychedelics with therapeutic intent.
• Exposure to psilocybin, or any other classic psychedelics during the past year or current depressive episode, and agreement not to use psychedelics for the duration of the study follow up
• Participants who are pregnant, nursing, or planning a pregnancy

• Aged ≥18 years at Screening
• Major depression without psychotic features
• If the current major depressive episode is the participant’s first lifetime episode of depression, the length of the current episode must be ≥6 months and ≤2 years at Screening
• MADRS total score ≥20 at Screening and Baseline
• TRD, defined as failure to respond to an adequate dose and duration of two, three, or four different pharmacological treatments for the current episode
• Successful discontinuation of all prohibited medications at least two weeks prior to the Baseline visit (if applicable)
• Please refer to the Protocol for the full list of inclusion criteria