E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment-Resistant Depression (P-TRD) |
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E.1.1.1 | Medical condition in easily understood language |
Treatment-Resistant Depression |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025463 |
E.1.2 | Term | Major depressive disorder, single episode |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025454 |
E.1.2 | Term | Major depressive disorder, recurrent episode |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess the long-term efficacy of psilocybin with respect to use of new antidepressant treatment, hospitalisations for depression, suicidality, and depressive severity rated using the Montgomery and Asberg Depression Rating Scale (MADRS) over a total of 52 weeks (compared across the 1 mg, 10 mg and 25 mg psilocybin groups from COMP 001). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: •To assess response, sustained response, remission and change in depression severity (compared across all treatment groups – 1 mg, 10 mg and 25 mg psilocybin in COMP 001 and 25 mg as an adjunct to SSRIs in COMP 003) over a total of 52 weeks •To evaluate the effect of psilocybin on functioning and associated disability compared across the groups over a total of 52 weeks
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1)Signed ICF 2)Each participant having completed the final study visit of either COMP 001 or COMP 003 3)Ability to complete all protocol required assessment tools (including having access to the internet in order to complete the digital assessments) without any assistance or alteration to the copyrighted assessments, and to comply with all study visits
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E.4 | Principal exclusion criteria |
1)Subject has any condition, for which in the opinion of the investigator, participation would not be in the interest of the subject eg participation could compromise the wellbeing of the participant or prevent, limit, or confound the protocol-specified assessments |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this long-term follow up study will be time to any of the following depression-related events (from baseline ie one day prior to single dose psilocybin administration dosing in the prior study) in participants recruited from the COMP 001 study (presented for the 1 mg , 10 mg, and 25 mg psilocybin therapy groups): •Initiation of new antidepressant treatment (first new antidepressant treatment in time period only) •Hospitalisation due to depression •Suicide attempt, suicide prevention, or completed suicide •Increased suicidality measured by worsening on MADRS item 10 i.e. either 1) a score of 5 or 6 on MADRS item 10; or 2) an increase of 2 points compared to Baseline in the prior study MADRS 10 score •Worsening in the MADRS clinician rated severity scale: i.e. a 5 point worsening compared to baseline score in the prior study at any timepoint post-baseline of the original study; or a worsening of ≥5 points (providing the highest score is ≥10) across two or more consecutive visits (in this case the first date of the ≥5 point increase will be classed as the event and at the final study visit the ≥5 point worsening will qualify as an event without need for confirmation at a subsequent visit) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: •Change in MADRS total score from Baseline of the prior study to 12 , 16, 20, 24, 28. 40, and 52 weeks post psilocybin •The proportion of participants with a response (defined as a ≥ 50% improvement in MADRS total score from Baseline of the prior study) at Week 12 , 16, 20, 24, 28, 40, and 52 post psilocybin •The proportion of participants with remission (defined as a MADRS total score ≤ 10) at Week 12, 16, 20, 24, 28, 40, and 52 post psilocybin •The proportion of participants who have a sustained response at Week 12, 16, 20, 24, 28, 40 and 52. Sustained response is defined as the proportion of patients fulfilling response criteria at any visit up to and including Week 3 post-dosing (in the lead-in studies), that also fulfills response criteria at all subsequent visits up to and including Week 12, 16, 20, 24, 28, 40, and 52 post psilocybin. Response is defined as ≥ 50% decrease in MADRS total score from Baseline of the prior study •Longitudinal depression severity: the difference in the area under the curve between 1mg, 10 mg, and 25 mg psilocybin monotherapy and 25 mg psilocybin adjunctive therapy over 52 weeks post-baseline in QIDS-SR-16 total score •Work and Social Adjustment (WSAS) score change from Baseline of the prior study to week 12, 18, 24, 30, 36, 42, 48 •Sheehan Disability Scale (SDS) score change from Baseline of the prior study to week 12, 16, 20, 24, 28, 40, and 52 post psilocybin
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 0 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Czech Republic |
Denmark |
Ireland |
Netherlands |
Portugal |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |