A Phase 3 Trial to Assess CYB003 in Major Depressive Disorder (EMBRACE)
Phase III, quadruple-blind, randomised, placebo-controlled trial (n=330) of CYB003 (8 mg and 16 mg; two dosing sessions ~3 weeks apart) as adjunctive treatment for major depressive disorder.
Randomised, parallel-group, quadruple-masked Phase III study evaluating two dose levels of CYB003 versus matching placebo as adjunctive therapy in adults with major depressive disorder on a stable antidepressant regimen.
Participants receive two medicine sessions approximately three weeks apart (8 mg or 16 mg CYB003 or placebo) with manualized psychological support provided throughout; primary outcomes assess efficacy, safety and tolerability.
Key safety exclusions include psychotic disorders, first-degree family history of schizophrenia/schizoaffective disorder/bipolar I, significant suicide risk within 12 months, and medications or conditions that increase serotonin syndrome risk.
Study Protocol
Preparation
sessions
Locations
UAB Psychiatry and Behavioral Neurology — Birmingham, Alabama, United States
Lighthouse Psychiatry — Gilbert, Arizona, United States
Pillar Clinical Research - Little Rock — Little Rock, Arkansas, United States
Behavioral Research Specialists, LLC — Glendale, California, United States
Sun Valley Research Center — Imperial, California, United States
CalNeuro Research Group — Los Angeles, California, United States
ATP Clinical Research — Orange, California, United States
NRC Research Institute — Orange, California, United States
Inland Psychiatric Medical Group Inc (IPMG Research) — San Juan Capistrano, California, United States
Psychedelic Science Institute — Santa Monica, California, United States
Stanford University — Stanford, California, United States
Yale School of Medicine - Connecticut Mental Health Center (CMHC) — New Haven, Connecticut, United States
CNS Healthcare — Jacksonville, Florida, United States
Accel Research Sites - Maitland — Maitland, Florida, United States
Aqualane Clinical Research — Naples, Florida, United States
Emory University Dept of Psychiatry and Behavioral Studies
Dosing
2 sessions
Integration
sessions
Therapeutic Protocol
support
Study Arms & Interventions
CYB003 8 mg
experimental
CYB003 8 mg in 2 dosing sessions approximately three weeks apart; adjunctive to stable antidepressant; manualized psychological support provided.
Interventions
Psilocybin8 mg
via Oral• two sessions• 2 doses total
Deuterated psilocin analogue; given adjunctive to current antidepressant.
Compound
Manualized psychological support throughout study (behavioural intervention).
CYB003 16 mg
experimental
CYB003 16 mg in 2 dosing sessions approximately three weeks apart; adjunctive to stable antidepressant; manualized psychological support provided.
Interventions
Psilocybin16 mg
via Oral• two sessions• 2 doses total
Deuterated psilocin analogue; given adjunctive to current antidepressant.
Compound
Manualized psychological support throughout study (behavioural intervention).
Placebo
placebo
Matching placebo in 2 dosing sessions approximately three weeks apart; manualized psychological support provided. Non-responders eligible for extension with CYB003.
Interventions
Placebo
via Oral• two sessions
Matching placebo.
Compound
Manualized psychological support throughout study (behavioural intervention).
Participants
Ages
18 – 85
Sexes
Male & Female
BMI
-
Psychosis History
Excluded
Inclusion 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.
Moderate to severe depression at Screening.
Participants have been on a stable dose of antidepressant medication at an adequate dose in the last 4 weeks prior to Screening.
Participant has a body mass index (BMI) of 40 kg/m2 or less (BMI ≤40 kg/m2), inclusive, at Screening.
Participants with well controlled hypertension.
Participant is able to refrain from smoking during the dosing session.
Participants must use a condom plus spermicide during the trial and for 12 weeks afterwards.
Participants of childbearing potential must agree to use a highly effective method of and 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
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.
Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first-degree relatives).
Significant suicide risk within 12 months of Screening.
Current or previous diagnosis of treatment-resistant MDD.
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.
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 hydroxytryptophan or St John's Wort within prior to trial medication administration.
Strenuous exercise prior to each clinic visit.
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.