Clinical Trials Register

Summary
EudraCT Number:	2018-003573-97
Sponsor's Protocol Code Number:	PSIDER
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-07-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-003573-97

A.3

Full title of the trial

A randomised, placebo controlled trial of psilocybin in treatment resistant depression: A feasibility study

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Trial of Psilocybin in Clinical Depression Resistant to Standard Treatments

A.3.2

Name or abbreviated title of the trial where available

Psilocybin TRD Feasibility RCT

A.4.1

Sponsor's protocol code number

PSIDER

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	King's College London
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	National Institute for Health Research Clinician Scientist Fellowship Programme (CS-2017-17-007)
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	King's College London
B.5.2	Functional name of contact point	Prof. Allan Young
B.5.3	Address:
B.5.3.1	Street Address	M2.16 (PO72). The Centre for Affective Disorders, The Institute of Psychiatry, Psychology & Neurosci
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE5 8AF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02078480088
B.5.5	Fax number	02078480298
B.5.6	E-mail	allan.young@kcl.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	South London & Maudsley NHS Foundation Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	National Institute for Health Research Clinician Scientist Fellowship Programme (CS-2017-17-007)
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	South London & Maudsley NHS Foundation Trust
B.5.2	Functional name of contact point	Prof. Allan Young
B.5.3	Address:
B.5.3.1	Street Address	M2.16 (PO72). The Centre for Affective Disorders, The Inst of Psychiatry, Psychology & Neuroscience
B.5.3.2	Town/ city	London
B.5.3.3	Post code	SE5 8AF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02078480088
B.5.5	Fax number	02078480298
B.5.6	E-mail	allan.young@kcl.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Psilocybin
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Psilocybin
D.3.9.1	CAS number	520-52-5
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Major depressive disorder

E.1.1.1

Medical condition in easily understood language

Clinical depression

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	PT
E.1.2	Classification code	10057840
E.1.2	Term	Major depression
E.1.2	System Organ Class	10037175 - Psychiatric disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the feasibility of a randomised, controlled trial design, in which a single dose of psilocybin 25mg PO vs placebo, is given to adult participants with treatment resistant major depressive disorder (TRD), under psychologically supportive conditions, with 6 weeks of follow up, by measuring recruitment rates, dropout rates and by estimating the variance of the primary outcome measure (MADRS) to inform upon the design of a phase 3 trial.

E.2.2

Secondary objectives of the trial

1)To assess the clinician-rated efficacy of psilocybin 25mg compared to placebo via:
a)The change in the MADRS total score from Baseline to 3 weeks after treatment
b)The proportion of participants who demonstrate a response to treatment( ≥50% decrease in MADRS total score) from Baseline to Week 3.
c)proportion of participants in remission( MADRS total score ≤10 at Week 3)
2)To assess the participant-rated efficacy of psilocybin 25mg compared to placebo via:
a)proportion of participants who demonstrate a response to treatment, ( a ≥50% decrease in QIDS-SR-16 total score) from Baseline (V2) to Week 3 (V6).
b)proportion of participants in remission, where remission is defined as a QIDS-SR-16 total score ≤5 at Week 3.
3)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).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age 25 - 80 years
• Fluent in the English language
• Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for a primary diagnosis of current single or recurrent episodes of MDD of at least moderate severity but without psychotic features as defined on the MINI 7.0. Positive and primary diagnoses on the MINI 7.0 will be subject to confirmation at clinical interview by a psychiatrist.
• 17-item HAM-D score ≥ 14.
• Have failed to respond to 2 or more antidepressants prescribed at the minimum effective dose for at least 6 weeks OR at least 1 antidepressant prescribed at the minimum effective dose for at least 6 weeks AND a course of evidence-based psychotherapy given for at least 6 sessions.
• For those aged ≥ 60 years, the first episode of depression must have started prior to their 60th birthday.

E.4

Principal exclusion criteria

• Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or bipolar 2) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of psychotic disorder (defined as meeting DSM-5 criteria for any psychotic disorder) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of drug or alcohol dependence syndrome (defined as meeting DSM-5 criteria for any dependence syndrome) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of any personality disorder (defined as meeting DSM-5 criteria for any personality disorder) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of any dementia (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist.
• Personal history of a ≥ 1 suicide attempt in the past year requiring hospitalization, defined using the CSSRS (Q6 (past year) = “y”) and clinical interview with a psychiatrist.
• Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin.
• Depression secondary to other medical conditions
• Medical diagnosis incompatible with psilocybin treatment
• Inability to provide a screening blood sample, urine sample or electrocardiogram. 
• Biochemical abnormalities (defined as falling outside the normal reference range) as evaluated by a full blood count, full biochemistry profile and thyroid function tests. Biochemical abnormalities must also be determined as clinically significant by a medical doctor to fulfil the criterion for exclusion.
• Electrocardiographic abnormalities, defined as any abnormality that is not normal sinus rhythm and determined as clinically significant by a medical doctor.
• Women of child bearing potential not using adequate contraception
• Pregnant or breast-feeding women.
• Those unable to give informed consent.
• Non-registration with a GP or failure to consent to sharing of the GP summary care record and any psychiatric assessments held.
• Those enrolled in another drug trial
• Hypersensitivity to the IMP or to any of the excipients or placebo

Participants will be excluded if they have a current diagnosis of ≥1 of:
• Uncontrolled diabetes
• Hypertension (defined as a systolic blood pressure ≥ 160mm/Hg or a diastolic blood pressure ≥ 100mm/Hg on three separate readings). All readings of systolic blood pressure ≥ 140mm/Hg or diastolic blood pressure ≥ 90mm/Hg will be reviewed by a clinician. Hypertension ascertained prior to dosing will be subject to clinical confirmation via collateral information from the GP or other source.
• Cardiac failure, defined as class IV of the New York Heart Association classification
• Renal failure, defined as ≥ stage 4 (GFR ≤ 29mL/min)
• Liver failure, defined as a clinical diagnosis of liver fibrosis, cirrhosis of the liver, liver failure or advanced liver disease.
• Any cardiac arrhythmia, except atrial fibrillation.
• Any form of epilepsy
Past diagnosis of ≥1 of:
• Cerebrovascular accident or intracerebral trauma.
• Myocardial infarction within 1 year prior to the screening visit.

E.5 End points

E.5.1

Primary end point(s)

Recruitment rates, dropout rates and estimation of the variance of the primary outcome measure (MADRS).

E.5.1.1

Timepoint(s) of evaluation of this end point

3 weeks after dosing

E.5.2

Secondary end point(s)

1) The change in the Montgomery-Asberg Depression Rating Scale total score from the Baseline Visit (V2 - 1 day prior to treatment) to Week 3 after treatment (V6).
2) The proportion of participants who demonstrate a response to treatment, where response to treatment is defined as a ≥50% decrease in MADRS total score from Baseline to Week 3.
3) The proportion of participants in remission, where remission is defined as a MADRS total score ≤10 at Week 3.
4) The proportion of participants who sustain a response up to Week 6, where response is defined as those with ≥50% decrease in MADRS total score on or before Week 3 and remaining at Week 6.
5) Time to event measures: restart antidepressant medication for any reason, restart medication for continuing depressive symptoms or 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.

Exploratory endpoints:
1) Change from baseline (V2) in the following outcome measures
a) The WSAS at week 6 (V7)
b) The QIDS-SR-16 at week 3 (V6)
c) The GAD-7 at week 3 (V6)

E.5.2.1

Timepoint(s) of evaluation of this end point

As above

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

Database lock

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1