Treatment-Resistant Depression (P-TRD) MedDRA version: 21.1 Level: LLT Classification code 10025454 Term: Major depressive disorder, recurrent episode System Organ Class: 100000004873 MedDRA version: 21.1 Level: LLT Classification code 10025463 Term: Major depressive disorder, single episode System Organ Class: 100000004873
Conditions
Sponsors
COMPASS Pathfinder, Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants meeting all the following inclusion criteria at Screening (V1) should be considered for admission into the study: 1. Signed Informed Consent Form (ICF). 2. 18 years of age or older at Screening (V1). 3. At least moderate MDD (single or recurrent episode as informed by DSM-5; if single episode, duration of = 3 months and =2 years) based on medical records, clinical assessment and documented completion of the version 7.0.2 MINI. 4. HAM-D-17 (17-item) score =18 at Screening (V1) and at Baseline (V2). 5. Failure to respond to an adequate dose and duration of 2, 3, or 4 pharmacological treatment for the current episode as determined through the MGH ATRQ and using the supplementary advice on additional antidepressants not included in MGH ATRQ (Appendix III). Augmentation with an add on treatment counts as a second treatment, provided it is approved for the adjunctive treatment of MDD in that country. 6. McLean Screening Instrument for Borderline Personality Disorder =65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: Participants meeting any of the following exclusion criteria at Screening (V1) will not be enrolled in the study: Psychiatric Exclusion Criteria: 1. Current or past history of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, or borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structure clinical interview (version 7.0.2 MINI). 2. Prior electroconvulsive therapy and/or intravenous ketamine for current episode. 3. Current cognitive behavioural therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of baseline. 4. Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening (V1). 5. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, at Screening or at Baseline, or; (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during subject interview. 6. Depression secondary to other severe medical conditions. 7. Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin, including exposure to psilocybin within the past year and use of psychedelics, such as ayahuasca, during the current depressive episode. General Medical Exclusion Criteria: 8. Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of child-bearing potential must have a negative urine pregnancy test at Screening (V1) and Baseline (V2). 9. Cardiovascular conditions: recent stroke (140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF. 10. Uncontrolled insulin-dependent diabetes. 11. Seizure disorder. 12. Positive urine drug screen for illicit drugs or drugs of abuse at V1 and/or V2. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator’s discretion in conjunction with the medical monitor. 13. Current enrolment in any investigational drug or device study or participation in such within 30 days of Screening (V1). 14. Current enrolment in an interventional study for depression or participation in such within 30 days of Screening (V1). 15. Abnormal and clinically significant results on the physical examination, vital signs, ECG, or laboratory tests at Screening (V1). 16. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main purpose of this study is to allow COMPASS to determine the optimal dose of psilocybin, either 10 mg or 25 mg. The intent of the primary efficacy analysis is to demonstrate superiority of at least one therapeutic dose of psilocybin (10 mg or 25 mg) versus the 1 mg psilocybin via the following objectives: The primary objective of this study is to evaluate the efficacy of psilocybin (25 mg or 10 mg) compared to 1 mg, administered under supportive conditions to adult participants with TRD, in improving depressive symptoms, as assessed by the change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline. Baseline is defined as the assessment score obtained on Day -1. The primary timepoint is Week 3; this variable will be analysed for the change from Baseline to Day 1, and Weeks 1, 3, 6, 9, and 12. ;Secondary Objective: The secondary objectives are: To assess the efficacy of psilocybin compared to 1 mg psilocybin on: o Proportion of participants with response defined as a = 50% decrease in MADRS total score from Baseline to Week 3. This will also be assessed at Day 1 and at Weeks 1, 6, 9, and 12. o The proportion of participants who have a sustained response at Week 12. Sustained response is defined as the proportion of patients fulfilling response criteria at any visit up to and including Week 3, that also fulfills response criteria at all subsequent visits up to and including Week 12. Response is defined as = 50% decrease in MADRS total score from Baseline. To evaluate the safety and tolerability of psilocybin in participants with TRD based on adverse events (AEs), changes in vital signs, and suicidal ideation/behaviour (measured using the Columbia-Suicide Severity Rating Scale [C SSRS]) score at all visits. ;Primary end point(s): The primary endpoint is the change in MADRS total score from Baseline (Day -1) to 3 weeks post psilocybin. ;Timepoint(s) of evaluation of this end point: 3 Weeks post psilocybin | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: • The proportion of participants with a response (defined as a =50% improvement in MADRS total score from Baseline) at Week 3 post-psilocybin. • The proportion of participants with remission (defined as a MADRS total score =10) at Week 3 post-psilocybin. • The proportion of participants who have a sustained response at Week 12.Sustained response is defined as the proportion of patients fulfilling response criteria at any visit up to and including Week 3, that also fulfills response criteria at all subsequent visits up to and including Week 12. Response is defined as = 50% decrease in MADRS total score from Baseline. • Time to event measures: restart antidepressant medication for any reason, restart medication for continuing depressive symptoms, and relapse from a previously recovered state (clinical judgement, supported by the QIDS-SR-16). Participants who withdraw from the study will be censored from the time to event analysis. ;Timepoint(s) of evaluation of this end point: See section E.5.2 | — |
Countries
Canada, Czechia, Czech Republic, Denmark, Finland, Germany, Ireland, Netherlands, Norway, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactEkaterina Malievskaia
COMPASS Pathfinder, Limited
Outcome results
None listed