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

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 85 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 330 participants

Study Arms

• Experimental Arm A CYB003 in 2 of 2 Dosing Sessions (EXPERIMENTAL)
  Arm A participants will receive 8 mg of CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. All Arm A participants will continue on their current antidepressants and receive psychological support throughout the study.
• Experimental Arm B CYB003 in 2 of 2 Dosing Sessions (EXPERIMENTAL)
  Experimental Arm B participants will receive 16 mg of CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. All Arm B participants will continue on their current antidepressants and receive psychological support throughout the study.
• Placebo Comparator: Arm C Placebo in 2 of 2 Dosing Session (PLACEBO_COMPARATOR)
  Participants will receive placebo in 2 of 2 medicine sessions, approximately three weeks apart. All Arm C participants will continue on their current antidepressants and receive psychological support throughout the study. Non-responders will be eligible to receive CYB003 in a subsequent extension trial.

Interventions

• DRUG: CYB003 — CYB003 is a deuterated psilocin analog.
• BEHAVIORAL: Psychological Support — Manualized psychological support performed by facilitator.

Primary Outcomes

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

Secondary Outcomes

• The Beck Depression Inventory - Second Edition (BDI-II) (Day -1, Day 21, Day 42 and Day 84/End of Trial.)
• The Clinical Global Impression Scale (CGI-S) (Screening Day-45, Baseline Day -1, Day 42, Day 84/End of Trial.)
• 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 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.)

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 bet

Trial 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
• ...and 10 more locations

Contact Information

• Clinical Development — CONTACT
  Phone: 877-361-4003
  Email: clinicaltrialsinfo@cybin.com

Study Officials

• Felix Mazer — STUDY_DIRECTOR
  Cybin IRL Limited

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