A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder

Official title

An Efficacy and Safety, Phase III, Multi-center, Double-Blind, Randomized Controlled Study Comparing 2 Active Doses of CYB003 and Placebo in Eligible Participants With Major Depressive Disorder

Overview

The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD. For more information about the EMBRACE study, including participating study locations, and to register your interest in learning more about participation, please visit the study website: https://embrace-mdd-trial.com/

Interventions

• Drug CYB003
  CYB003 is a deuterated psilocin analog.
• Behavioral Psychological Support
  Manualized psychological support performed by facilitator.

Primary outcome measures

• Montgomery-Asberg Depression Scale (MADRS) [Time frame: Screening Day-45, Baseline, Day -1, Day 21, Day 42, Day 63 and Day 84/End of Trial.]

Secondary outcome measures (4)

• The Beck Depression Inventory - Second Edition (BDI-II) [Time frame: Day -1, Day 21, Day 42 and Day 84/End of Trial.]
• The Clinical Global Impression Scale (CGI-S) [Time frame: Screening Day-45, Baseline Day -1, Day 42, Day 84/End of Trial.]
• The Generalized Anxiety Disorder 7-Item Scale (GAD-7) [Time frame: Baseline Day -1, Day 21, Day 42, Day 63 and Day 84/End of Trial.]
• The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) [Time frame: Day -1, Day 21, Day 42 and Day 84/End of Trial.]

Eligibility criteria

Inclusion criteria

Participants must meet all the following criteria to be included in the trial:

• Age18 to 85 years.
• Participant has a diagnosis of MDD (single or recurrent episode as defined by DSM-5 TR \[if single episode, duration of ≥4 weeks and ≤24 months\] and established as per evaluation by the Investigator. The first MDD episode must have occurred prior to age 60.
• Moderate to severe depression at Screening and Baseline, independently confirmed.
• Participants have been on a stable dose of antidepressant medication (label specified) at an adequate dose in the last 4 weeks prior to Screening and has had an inadequate response (less than 50% improvement), as judged by the Investigator.
• Participant has a body mass index (BMI) of 40 kg/m2 or less (BMI ≤40 kg/m2), inclusive, at Screening.
• Participant is able to refrain from nicotine use during the dosing session (up to 8 hours).
• Participants capable of producing sperm must use a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication, if their partner is a person of childbearing potential.
• Participants of childbearing potential who have a partner capable of producing sperm must agree to use a highly effective method of contraception in combination with the use of a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication. Such participants must have a negative pregnancy test at Screening and Day 1 prior to dosing.
• Participants of non-childbearing potential who are or were capable of producing eggs (ova) must have been postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
• Participants have provided written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.

Exclusion criteria

Participants with any of the following characteristics/conditions will be excluded from trial participation:

• Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder, brief psychotic disorder, current or previous history of bipolar disorder, or current borderline personality disorder.
• Participants with a medical diagnosis of attention deficit hyperactivity disorder (ADHD) will be excluded if currently taking medication for ADHD.
• Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first-degree relatives).
• Significant suicide risk within the past 6 months, during the Screening Period, or at Baseline; or (b) suicidal behaviors within 12 months of Screening; or (c) clinical assessment of significant suicidal risk during clinical interview; or (d) non-suicidal self-injury within 12 months of Screening.
• Current or previous diagnosis of treatment-resistant MDD, defined as failure to respond to 2 or more antidepressant treatments of 2 different classes given at an adequate dose (label specified) for an adequate duration as judged by the Investigator and clinical interview.
• Has had electroconvulsive treatment, transcranial magnetic stimulation, deep brain stimulation, or vagal nerve stimulation for any episode of MDD in the last 6 months.
• Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressants, mirtazapine, trazodone, moclobemide, buspirone, or an antipsychotic or mood stabilizer. Note: if receiving these medications are for another indication, they must be discontinued ≥ 14 days or 5 half-lives, whichever is longer, prior to Day 1.
• Participant report of (or if available in medical record) exposure to psilocin, or 5-HT2a receptor agonists, or any other psychedelics, such as ayahuasca, mescaline, lysergic acid diethylamide, peyote, or 3,4-methylenedioxymethamphetamine, more than 10 times over the participant's lifetime or any psychedelic use within 12 months prior to Screening.
• Participant report of (or if available in medical record) treatment with ketamine or S-ketamine use within 6 months prior to Screening.
• Clinically relevant history of abnormal physical health interfering with the trial (including but not limited to, neurological, cardiovascular, respiratory, gastrointestinal \[including dyspepsia or gastroesophageal reflux disease\], hepatic, or renal disorder).
• Has hypothyroidism or hyperthyroidism, unless controlled on appropriate medication.
• Current diagnosis of uncontrolled hypertension or an arrhythmia, or clinically relevant abnormal results for heart rate.
• Participants have a presence or relevant history of organic brain disorders.
• Participant is taking or has taken OTC doses of 5-HTP or St John's Wort within prior to trial medication administration.
• Donation of blood or plasma within 4 weeks prior to first dosing and until 4 weeks after final dosing.
• Participants capable of producing sperm who will not abstain from sperm donation between first dosing and 12 weeks after final dosing.
• Participants of childbearing potential who are pregnant, breastfeeding, planning to conceive or unwilling to abstain from egg (ova) donation between first dosing and 12 weeks after final dosing.
• History of serotonin syndrome.
• Unwilling to consent to audio and video recording of psychological support and dosing sessions.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 33 centers

• UAB Psychiatry and Behavioral Neurology — Birmingham
• Lighthouse Psychiatry — Gilbert
• Pillar Clinical Research - Little Rock — Little Rock
• Behavioral Research Specialists, LLC — Glendale
• Sun Valley Research Center — Imperial
• CalNeuro Research Group — Los Angeles
• ATP Clinical Research — Orange
• NRC Research Institute — Orange
• … and 25 more centers

United Kingdom · 12 centers

• Cambridge University Hospital NHS — Cambridge
• Clerkenwell Health - Doncaster — Doncaster
• NHS Research Scotland — Edinburgh
• Queen Elizabeth University Hospital — Glasgow
• St Pancras Clinical Research — London
• King's College London — London
• Clerkenwell Health - Welbeck Street — London
• Re:Cognition Health — London
• … and 4 more centers

Poland · 6 centers

• Uniwersytecki Szpital Kliniczny W Białymstoku — Bialystok
• Promente - Centrum Neurologii i Psychogeriatrii w Bydgoszczy — Bydgoszcz
• UCK — Gdansk
• Centrum Badan Klinicznych PI-House Sp. z o.o — Gdansk
• MTZ Clinical Research Powered by Pratia — Warsaw
• Department of Pharmacology and Physiology of CNS — Warsaw

Australia · 5 centers

• Royal Prince Alfred Hospital — Camperdown
• Thompson Brain & Mind Healthcare (TBMH) — Maroochydore
• Ramsay Clinic — Melbourne
• Neurocentrix Research — Melbourne
• Monash University - Notting Hill — Notting Hill

Germany · 4 centers

• Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarland — Homburg
• Charité Universitaetsmedizin Berlin — Berlin
• University Hospital Frankfurt — Frankfurt am Main
• Central Institute of Mental Health — Mannheim

Czechia · 3 centers

• Institute of neuropsychiatric Care (INEP) — Prague
• Psyon s.r.o. — Prague
• A-SHINE s.r.o. — Předměstí

Greece · 3 centers

• Eginitio Hospital — Athens
• Attikon University Hospital — Athens
• Papageorgiou General Hospital — Thessaloniki

Ireland · 2 centers

• Sheaf House - Tallaght Adult Mental Health Service — Dublin
• La Nua Day Hospital Mental Health Centre — Galway

Identifiers

NCT: NCT06793397 · CYB003-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗