Depression, Depression Disorder, Depression Disorders, Depression in Adults, Depression - Major Depressive Disorder, Major Depressive Disorder (MDD)
Conditions
Keywords
MDD, Psychedelic, Depression, Major Depressive Disorder, CYB003, CYB003-001, CYB003-002, Psilocybin, psilocin-7438
Brief summary
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
DRUGCYB003
CYB003 is a deuterated psilocin analog.
BEHAVIORALPsychological Support
Manualized psychological support performed by facilitator.
Sponsors
Cybin IRL Limited
Worldwide Clinical Trials
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Scale (MADRS) | Screening Day-45, Baseline, Day -1, Day 21, Day 42, Day 63 and Day 84/End of Trial. | The MADRS is a 10-item scale with ratings based on a clinical interview which moves from broadly phased questions about symptoms to more detailed ones allowing a precise rating of severity. The total score ranges 0-60, higher scores denote greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Beck Depression Inventory - Second Edition (BDI-II) | Day -1, Day 21, Day 42 and Day 84/End of Trial. | The Beck Depression Inventory-Second Edition (BDI-II) is a 21-question multiple-choice self-report inventory, assessing depressive symptoms and severity. Each question is scored on a scale value of 0 to 3, with higher total scores indicating more severe depressive symptoms. Each of the 21 items corresponding to a symptom of depression is summed to give a single score for the BDI-II, so the total score possible is 63 and minimum if everything is zero would be 0. |
| The Clinical Global Impression Scale (CGI-S) | Screening Day-45, Baseline Day -1, Day 42, Day 84/End of Trial. | The Clinical Global Impression Scale is a clinician-rated instrument comprised of 3 global measures: severity of illness, global improvement and efficacy index. Only the severity of illness ang global improvement measures will be utilized for this trial. Higher score means more severe symptomology, worse outcome. CGI-S scoring is as follows: 1. = Normal, not at all ill 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill patients |
| The Generalized Anxiety Disorder 7-Item Scale (GAD-7) | Baseline Day -1, Day 21, Day 42, Day 63 and Day 84/End of Trial. | The Generalized Anxiety Disorder 7-Item Scale (GAD-7) is a 7-item self reported assessment that measures the severity of generalized anxiety disorder symptoms. Participants respond to each item using a 4-point scale from 0 to 3. Participants choose one of 4 severity scores associated with problems related to the common anxiety disorders to indicate the degree to which these problems caused functional and/or social difficulties. A total score is obtained by the sum of all total column values, higher scores indicate more functional/social impairment/difficulties. Score range is as follows: Scores represent: 0 - 4 = Minimal anxiety 5 - 9 = Mild anxiety 10 - 14 = Moderately anxiety 15 - 21 = Severe anxiety |
| The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) | Day -1, Day 21, Day 42 and Day 84/End of Trial. | The original Quality of Life Enjoyment and Satisfaction Questionnaire is a 93 item, participant facing, self reported measure used to evaluate intervention-related changes in quality of life, divided int the following sections: physical health, feelings, work, household duties, school, leisure time activities, social relations and general activities. The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) version will be used in this trial. Each item rated on a 5-point scale ranging from 1 (very poor) to 5 (very good), higher score indicates greater satisfaction. The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score. The last two items are not included in the total score but are standalone items. The raw total score ranges from 14 to 70. So the minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70 |
Countries
Australia, Czechia, Germany, Greece, Ireland, Poland, United Kingdom, United States
Contacts
CONTACTClinical Development
STUDY_DIRECTORFelix Mazer
Cybin IRL Limited
Outcome results
None listed