A Phase III, Placebo-Controlled, Randomized, Double-Blind Trial of Oral Doses of CYB003 to Assess Combined Safety and Efficacy in Humans With Major Depressive Disorder

Official Summary

The purpose of this study is to examine the efficacy, safety, and tolerability of CYB003 compared to matching placebo as adjunctive treatment in participants with MDD.

Eligibility Requirements

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

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 220 participants

Study Arms

• Experimental Arm A: CYB003 in 2 of 2 Dosing Sessions (EXPERIMENTAL)
  Arm A participants will receive 16 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.
• Placebo Comparator Arm B: Placebo in 2 of 2 Dosing Sessions (PLACEBO_COMPARATOR)
  Arm B participants will receive placebo in 2 of 2 Dosing Sessions, approximately three weeks apart. All Arm B 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 facilitators
• DRUG: Placebo — Placebo

Primary Outcomes

• Montgomery-Åsberg Depression Rating Scale (MADRS) (Screening Day-45, Baseline Day-1, Day 2, Day 10, Day 21, Day 23, Day 31, and Day 42 (End of Treatment))

Secondary Outcomes

• The Beck Depression Inventory-Second Edition (BDI-II) (Baseline Day-1, Day 21, and Day 42 (End of Treatment))
• The Clinical Global Impression Scale (CGI-S) (Screening Day-45, Baseline Day-1, and Day 42 (End of Treatment))
• The Generalized Anxiety Disorder 7-item scale (GAD-7) (Baseline Day-1, Day 21, and Day 42 (End of Treatment))
• The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) (Baseline Day-1, Day 21, and Day 42 (End of Treatment))

Eligibility Criteria

Inclusion Criteria:

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

* Aged 18 to 85 years inclusive, at Screening
* 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.
* Depression is of moderate to severe degree at Screening and Baseline, independently confirmed by additional clinical assessments
* Participant has been on a stable dose of a single antidepressant medication at an adequate dose (label specified) for an adequate duration in the last month 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)
* Registered with a healthcare professional who can confirm the diagnosis and previous treatments received by the participant.
* 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 (i.e., failure rate less than 1% when used consistently and correctly) 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.
* Female participants who were capable of producing eggs (ova) must agree that the only exclusion from the requirement for contraception during the trial is to be postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for at least 12 months, and a serum follicle-stimulating hormone level in the menopausal range, unless the participant is taking hormone replacement therapy or is using hormonal contraception.
* Participant has 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 antidepressant, mirtazapine, trazodone, moclobemide, buspirone, ketamine or S-ketamine, or an antipsychotic or mood stabilizer for MDD. Note: if receiving these medications 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 as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including but not limited to, neurologica

Trial Locations

• Scottsdale Research Institute, Phoenix, Arizona, United States
• Mountain Clinical Trials, Phoenix, Arizona, United States
• Noble Clinical Research, Tucson, Arizona, United States
• Del Sol Research Management, Tucson, Arizona, United States
• CenExel CIT (Clinical Innovations, Inc), Bellflower, California, United States
• Kadima Neuropsychiatry Institute, La Jolla, California, United States
• Bespoke Treatment/Lipov Medical Group, Los Angeles, California, United States
• Catalina Research Institute, Montclair, California, United States
• Excell Research, Inc, Oceanside, California, United States
• Open Mind Therapeutics, San Francisco, California, United States
• ...and 10 more locations

Contact Information

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

Study Officials

• Clinical Development — STUDY_CHAIR
  Cybin IRL Limited

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