|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Depression that has not improved with other treatments.
|Psychiatry and Psychology [F] - Mental Disorders [F03]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10037175 - Psychiatric disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|Primary efficacy objective:
• To determine the efficacy of a single day individualized dosing regimen (IDR) of GH001 compared
with placebo in improving depressive symptoms as assessed by MADRS in patients with
treatment-resistant depression (TRD) at the end of the 7-day double-blind (DB) Part 1.
|Secondary objectives of the trial
|Other efficacy objectives:
• To determine the effect of a single day IDR of GH001 compared with placebo on depressive symptoms
as assessed by MADRS, global disease severity as assessed by CGI-S, anxiety as assessed by HAM-A,
and quality of life as assessed by Q-LES-Q-SF in patients with TRD at the end of the 7-day DB Part 1.
• To determine the effect of GH001 IDR as needed on depressive symptoms as assessed by MADRS,
global disease severity as assessed by CGI-S, anxiety as assessed by the HAM-A, and quality of life as
assessed by Q-LES-Q-SF in patients with TRD during the 6-month open-label extension (OLE) Part 2.
For full details please refer to the Protocol.
|Trial contains a sub-study
|Principal inclusion criteria
|1. Is in the age range between 18 and 64 years (inclusive) at the time of informed consent.
2. Meets the trial criteria for TRD as assessed by a study psychiatrist:
a. Meets the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for single-episode MDD or recurrent MDD, without psychotic features confirmed by the Mini-International Neuropsychiatric Interview (MINI)
b. The current MDE must be deemed “valid” based upon the Massachusetts General Hospital State versus trait Assessability Face and Ecological validity Rule of 3Ps (MGH SAFER) criteria interview.
c. Had nonresponse (≤25% improvement) to ≥2 and ≤5 oral antidepressant treatments started during the current episode of depression
|Principal exclusion criteria
|1. Has, based on history, psychiatric assessment, and evaluation of the MINI during the screening period, a first MDD episode after age 60, a current or prior diagnosis of a psychotic disorder, MDD, or other mood disorder with psychotic features, bipolar disorder, obsessive compulsive disorder, posttraumatic stress disorder, autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual disability, antisocial personality disorder, schizotypal personality disorder, or any other psychiatric comorbidity that renders the patient unsuitable for the trial according to a study psychiatrist.
2. Has significant suicide risk as defined by (a) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, during the screening period, or at Baseline; or (b) suicidal behaviors within the past year; or (c) clinical assessment of significant suicidal risk during clinical interview; or (d) non-suicidal self-injury within the past year.
3. Has 1 or more first degree relatives with a current or prior diagnosis of bipolar disorder, psychotic disorder, or other mood disorder (including MDD) with psychotic features.
4.Undergoing systematic psychotherapy (including cognitive behavioral therapy [CBT]) that is planned to be modified or planning to initiate psychotherapy during the trial. CBT must have been ongoing for the last 3 months prior to Baseline.
5. Has any current or past clinically significant condition (e.g., severe infection, severe pulmonary disease, uncontrolled hypertension, uncontrolled diabetes, severe cardiovascular disease, myocardial infarction or clinically significant arrythmia within the past year, severe hepatic or severe renal failure, brain disorder including seizure, stroke, dementia, degenerative neurologic diseases, meningitis, encephalitis, and head injury with loss of consciousness) that may interfere with the interpretation of the trial results, constitute a health risk for the patient, or that otherwise renders the patient unsuitable for the trial according to the investigator’s judgement.
6. Fulfils criteria for DSM 5 alcohol or substance use disorder (excluding tobacco and caffeine use disorders) within the preceding 1 year, as assessed via the MINI.
7. Takes or has taken disallowed recent or concomitant treatments or it is anticipated that the patient will require treatment with at least 1 of the disallowed concomitant treatments during the trial.
8. Has previously experienced a significant adverse reaction to a hallucinogenic or psychedelic drug (e.g., psilocybin, Psilocybe spp. mushrooms, 5 MeO DMT, DMT, ayahuasca, LSD, mescaline) according to the investigator’s judgement.
|E.5 End points
|Primary end point(s)
• Mean change in MADRS from Baseline to Day 7.
|Timepoint(s) of evaluation of this end point
|The analysis of the primary efficacy endpoint, change in MADRS from Baseline to D7, will be performed on the
FAS by analysis of covariance with treatment and Baseline MADRS score in the model.
|Secondary end point(s)
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
|Other trial design description
|Open-label extension to follow the DB, randomized and placebo- controlled phase
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months