Study NCT03775200
The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression (P-TRD)
Submitted Date:  February 7, 2023 (v29)
Quality Control Review Has Not Concluded

Note: The results information displayed below has not completed the quality control (QC) review process. ClinicalTrials.gov must post results information for applicable clinical trials (ACTs) within 30 days of submission, even if the submission has not completed the QC review process. The study sponsor or investigator is responsible for ensuring the results information meets the QC review criteria.

This submission includes brief standardized QC review comments added by the National Library of Medicine (NLM). These comments indicate the location of apparent errors, deficiencies, or inconsistencies. For more information, see the Final Rule (42 CFR Part 11) Information page.


Open or close this module Study Identification
Unique Protocol ID: COMP001
Brief Title: The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression (P-TRD)
Official Title: The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression
Secondary IDs:
Open or close this module Study Status
Record Verification: February 2023
Overall Status: Completed
Study Start: March 1, 2019
Primary Completion: July 30, 2021 [Actual]
Study Completion: September 27, 2021 [Actual]
First Submitted: December 11, 2018
First Submitted that
Met QC Criteria:
December 11, 2018
First Posted: December 13, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: March 7, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: COMPASS Pathways
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression
Detailed Description: The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression - a dose-ranging study
Open or close this module Conditions
Conditions: Treatment Resistant Depression
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 233 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Low dose
Low dose Psilocybin
Drug: Psilocybin
Dose-finding
Experimental: Medium dose
Medium dose Psilocybin
Drug: Psilocybin
Dose-finding
Experimental: High dose
High dose Psilocybin
Drug: Psilocybin
Dose-finding
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Montgomery Asberg Depression Rating Scale (MADRS) Change From Baseline to Week 3
[ Time Frame: Change from Baseline to Week 3 ]

MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response >= 50% decrease and remission <= 10 total score.
2. MADRS Change From Baseline to Week 3, Sensitivity Analysis
[ Time Frame: Change from Baseline to Week 3 ]

MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response >= 50% decrease and remission <= 10 total score.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Diagnosis of TRD

Exclusion Criteria:

  • Other comorbidities
Open or close this module Contacts/Locations
Locations: United States, California
Kadima Neuropsychiatry Institute
La Jolla, California, United States, 92037
Altman Clinical and Translational Research Institute, University of California
San Diego, California, United States, 92093
Stanford Department of Psychiatry
Stanford, California, United States, 94305
United States, Georgia
Mood and Anxiety Disorders Program Emory University School of Medicine
Atlanta, Georgia, United States, 30329
United States, Louisiana
Ray Worthy Psychiatry LLC
New Orleans, Louisiana, United States, 70123
United States, Maryland
Sheppard Pratt Health System
Baltimore, Maryland, United States, 21204
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
United States, Texas
UT Center of Excellence on Mood Disorders, University of Texas Health Science Center
Houston, Texas, United States, 77054
Canada, Ontario
Canadian Rapid Treatment Centre of Excellence
Mississauga, Ontario, Canada
Centre for Addiction and Mental Health
Toronto, Ontario, Canada
Czechia
National Institute of Mental Health Czech Republic
Klecany, Czechia
Denmark
Enhed for Psykiatrisk Forskning, Psykiatrien i Aalborg
Aalborg, Denmark
Germany
Charite╠ü - Universita╠łtsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin
Berlin, Germany, 12203
Ireland
Tallaght University Hospital
Dublin, Ireland
Netherlands
Groningen University Medical Centre
Groningen, Netherlands
Leiden University Medical Centre
Leiden, Netherlands
Utrecht University Medical Centre
Utrecht, Netherlands
Portugal
Unidade de Neuropsiquiatria, Centro Clinico Champalimaud
Lisboa, Portugal
Spain
Hospital de Dia Numancia
Barcelona, Spain
Institute Hospital del Mar of Medical Research (IMIM)
Barcelona, Spain
United Kingdom
St. Pancras Clinical Research
London, United Kingdom, EC2Y 8EA
Kings College London, Institute of Psychiatry, Psychology and Neurology
London, United Kingdom
Greater Manchester Mental Health Foundation Trust
Manchester, United Kingdom
United Kingdom, Avon
Clinical Research and Imaging Centre
Bristol, Avon, United Kingdom
United Kingdom, Tyne And Wear
Wolfson Research Centre, Campus for Ageing and Vitality
Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE4 5PL
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: July 22, 2019
Uploaded: 01/31/2023 06:19
File Name: Prot_000.pdf
Statistical Analysis Plan
Document Date: October 26, 2021
Uploaded: 02/07/2023 08:25
File Name: SAP_001.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details First patient first visit: 3 January 2019 Last patients last visit: 27 September 2021
Pre-assignment Details
 
Arm/Group Title 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Arm/Group Description 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin

Quality Control Review Comment provided by the National Library of Medicine:

  1. Information here appears inconsistent with information in other parts of the record.
Period Title: Overall Study
Started 79 75 79
Completed 74 66 69
Not Completed 5 9 10
Open or close this module Baseline Characteristics
Arm/Group Title25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 PsilocybinTotal
Arm/Group Description25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 PsilocybinTotal of all reporting groups
Overall Number of Baseline Participants 79 75 79 233
Baseline Analysis Population Description
Age, Categorical
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed79 Participants75 Participants79 Participants233 Participants
<=18 years
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
76
96.2%
73
97.33%
77
97.47%
226
97%
>=65 years
3
3.8%
2
2.67%
2
2.53%
7
3%
Age, Continuous [1]
Mean (Standard Deviation)
Unit of measure: years
Number Analyzed79 Participants75 Participants79 Participants233 Participants
40.2(12.19)40.6(12.76)38.7(11.71)39.8(12.19)
 
[1]Measure Description: Age at Screening
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed79 Participants75 Participants79 Participants233 Participants
Female
35
44.3%
34
45.33%
43
54.43%
112
48.07%
Male
44
55.7%
41
54.67%
36
45.57%
121
51.93%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed79 Participants75 Participants79 Participants233 Participants
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
4
5.06%
3
4%
5
6.33%
12
5.15%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
4
5.06%
0
0%
1
1.27%
5
2.15%
White
70
88.61%
72
96%
73
92.41%
215
92.27%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
1
1.27%
0
0%
0
0%
1
0.43%
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed79 Participants75 Participants79 Participants233 Participants
Canada
2226
Netherlands
17161750
United States
32323296
Czechia
3227
Ireland
33511
Denmark
3238
United Kingdom
11101233
Portugal
1012
Germany
2204
Spain
56516
Open or close this module Outcome Measures
1. Primary Outcome:
Title Montgomery Asberg Depression Rating Scale (MADRS) Change From Baseline to Week 3
Description MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response >= 50% decrease and remission <= 10 total score.
Time Frame Change from Baseline to Week 3
Outcome Measure Data
Analysis Population Description
The full analysis set includes all participants randomised who receive study drug and have at least 1 post-dose efficacy assessment.
 
Arm/Group Title25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 Psilocybin
Arm/Group Description25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 Psilocybin
Overall Number of Participants Analyzed79 75 79
Mean (Standard Deviation)
Unit of Measure: units on a scale
-12(12.98) -8.9(10.94) -6.8(11.10)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group Selection25 mg COMP360 Psilocybin, 1 mg COMP360 Psilocybin
CommentsThe primary analysis was the comparison between COMP360 (25 mg or 10 mg) versus COMP360 1 mg. The null hypothesis was that there was no difference in mean change from Baseline in MADRS total score at Week 3 for COMP360 25 mg or COMP360 10 mg versus COMP360 1 mg. The alternative hypothesis was that were was a difference in mean change from Baseline in MADRS total score at Week 3 for COMP360 25 mg or COMP360 10 mg versus COMP360 1 mg.
Type of Statistical TestOther
CommentsFor this primary analysis, a sample size of 216 randomised participants (72:72:72) will provide 90% power at the alpha = 0.05 level to detect a 6-point difference in average MADRS total score between the optimal therapeutic dose of COMP360 and COMP360 1 mg, assuming the common standard deviation (SD) is 11.0.
Statistical Test of HypothesisP-Value<0.05
Comments[Not specified]
MethodMixed Models Analysis
CommentsHypothetical strategy estimand - missing not at random (MNAR) and missing at random (MAR) imputation for missing data.
Method of EstimationEstimation ParameterLeast Mean Square Difference
Estimated Value-6.6
Confidence Interval(2-sided) 95%
-10.2 to -2.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.86
Estimation CommentsLSM difference of COMP360 25 mg compared to COMP360 1 mg.
2. Primary Outcome:
Title MADRS Change From Baseline to Week 3, Sensitivity Analysis
Description MADRS is a clinician-rated scale measuring depression symptom severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of between 0 to 60; higher scores denote greater severity. Response >= 50% decrease and remission <= 10 total score.
Time Frame Change from Baseline to Week 3
Outcome Measure Data
Analysis Population Description
The per-protocol analysis set includes all participants in the Full Analysis Set who do not have a protocol deviation that is thought to significantly affect the integrity of the participant's efficacy data.
 
Arm/Group Title25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 Psilocybin
Arm/Group Description25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 Psilocybin
Overall Number of Participants Analyzed77 65 68
Mean (Standard Deviation)
Unit of Measure: units on a scale
-12(12.98) -8.9(11.11) -6.7(11.18)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group Selection25 mg COMP360 Psilocybin, 1 mg COMP360 Psilocybin
CommentsSensitivity analysis of the primary endpoint using the per-protocol analysis set.
Type of Statistical TestOther
Comments[Not specified]
Statistical Test of HypothesisP-Value<0.05
Comments[Not specified]
MethodMixed Models Analysis
CommentsHypothetical strategy estimand - MNAR and MAR imputation for missing data.
Method of EstimationEstimation ParameterLeast Mean Square Difference
Estimated Value-5.6
Confidence Interval(2-sided) 95%
-9.4 to -1.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.93
Estimation Comments[Not specified]
Open or close this module Adverse Events
 
Time Frame Up to 12 Weeks
Adverse Event Reporting Description The Safety Analysis Set included all randomised participants who received study drug.
 
Arm/Group Title 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
Arm/Group Description 25 mg COMP360 Psilocybin 10 mg COMP360 Psilocybin 1 mg COMP360 Psilocybin
All-Cause Mortality
  25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 Psilocybin
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 0 / 79 (0%)0 / 75 (0%)0 / 79 (0%)
Serious Adverse Events
  25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 Psilocybin
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 5 / 79 (6.33%)6 / 75 (8%)1 / 79 (1.27%)
General disorders
Drug withdrawal syndrome † A 1 / 79 (1.27%)10 / 75 (0%)00 / 79 (0%)0
Psychiatric disorders
Adjustment disorder with anxiety † A 1 / 79 (1.27%)10 / 75 (0%)00 / 79 (0%)0
Adjustment disorder with mixed anxiety and depressed mood † A 1 / 79 (1.27%)10 / 75 (0%)00 / 79 (0%)0
Depression † A 0 / 79 (0%)01 / 75 (1.33%)10 / 79 (0%)0
Intentional self-injury † A 2 / 79 (2.53%)22 / 75 (2.67%)21 / 79 (1.27%)2
Suicidal behaviour † A 3 / 79 (3.8%)30 / 75 (0%)00 / 79 (0%)0
Suicidal ideation † A 2 / 79 (2.53%)22 / 75 (2.67%)30 / 79 (0%)0
Surgical and medical procedures
Hospitalisation † A 0 / 79 (0%)01 / 75 (1.33%)10 / 79 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 23.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  25 mg COMP360 Psilocybin10 mg COMP360 Psilocybin1 mg COMP360 Psilocybin
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 60 / 79 (75.95%)51 / 75 (68%)50 / 79 (63.29%)
Gastrointestinal disorders
Abdominal pain upper † A 4 / 79 (5.06%)42 / 75 (2.67%)21 / 79 (1.27%)1
Nausea † A 18 / 79 (22.78%)197 / 75 (9.33%)74 / 79 (5.06%)4
General disorders
Fatigue † A 12 / 79 (15.19%)125 / 75 (6.67%)57 / 79 (8.86%)8
Musculoskeletal and connective tissue disorders
Back pain † A 6 / 79 (7.59%)60 / 75 (0%)03 / 79 (3.8%)4
Myalgia † A 5 / 79 (6.33%)52 / 75 (2.67%)21 / 79 (1.27%)1
Nervous system disorders
Dizziness † A 6 / 79 (7.59%)61 / 75 (1.33%)11 / 79 (1.27%)1
Headache † A 27 / 79 (34.18%)3416 / 75 (21.33%)2220 / 79 (25.32%)30
Paraesthesia † A 3 / 79 (3.8%)34 / 75 (5.33%)41 / 79 (1.27%)1
Psychiatric disorders
Anxiety † A 7 / 79 (8.86%)713 / 75 (17.33%)163 / 79 (3.8%)3
Depressed mood † A 3 / 79 (3.8%)35 / 75 (6.67%)54 / 79 (5.06%)5
Depression † A 4 / 79 (5.06%)45 / 75 (6.67%)55 / 79 (6.33%)5
Euphoric mood † A 4 / 79 (5.06%)45 / 75 (6.67%)54 / 79 (5.06%)5
Insomnia † A 8 / 79 (10.13%)811 / 75 (14.67%)1114 / 79 (17.72%)16
Irritability † A 4 / 79 (5.06%)42 / 75 (2.67%)21 / 79 (1.27%)1
Mood altered † A 7 / 79 (8.86%)83 / 75 (4%)31 / 79 (1.27%)1
Panic reaction † A 4 / 79 (5.06%)41 / 75 (1.33%)11 / 79 (1.27%)1
Suicidal ideation † A 5 / 79 (6.33%)53 / 75 (4%)34 / 79 (5.06%)5
Thinking abnormal † A 0 / 79 (0%)04 / 75 (5.33%)40 / 79 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 23.0
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact:
Name/Official Title:
Medical Director
Organization:
Compass Pathways
Phone:
07443136539
Email:
info@compasspathways.com

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