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

NCT06793397 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CYB003-003
• Study Type: interventional
• Target: 330
• Locations: 8 countries
• Sites: 67

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.

Conditions

Major Depressive Disorder (MDD); Depression Disorders; Depression Disorder; Depression; Depression in Adults; Depression - Major Depressive Disorder

Keywords

MDD; Psychedelic; Depression; Major Depressive Disorder; CYB003; CYB003-001; CYB003-002; Psilocybin; psilocin-7438

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Scale (MADRS)

  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.

  Screening Day-45, Baseline, Day -1, Day 21, Day 42, Day 63 and Day 84/End of Trial.

Secondary Outcomes (4)

• 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.

Study Arms (3)

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.

Drug: CYB003; Behavioral: Psychological Support

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.

Drug: CYB003; Behavioral: Psychological Support

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.

Behavioral: Psychological Support

Interventions

Psychological Support BEHAVIORAL

Manualized psychological support performed by facilitator.

Experimental Arm A CYB003 in 2 of 2 Dosing Sessions; Experimental Arm B CYB003 in 2 of 2 Dosing Sessions; Placebo Comparator: Arm C Placebo in 2 of 2 Dosing Session

CYB003 DRUG

CYB003 is a deuterated psilocin analog.

Experimental Arm A CYB003 in 2 of 2 Dosing Sessions; Experimental Arm B CYB003 in 2 of 2 Dosing Sessions

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cybin IRL Limited: lead
• Worldwide Clinical Trials: collaborator

Study Sites (67)

UAB Psychiatry and Behavioral Neurology

Birmingham, Alabama, 35209, United States

RECRUITING

Lighthouse Psychiatry

Gilbert, Arizona, 85234, United States

RECRUITING

Pillar Clinical Research - Little Rock

Little Rock, Arkansas, 72204, United States

NOT YET RECRUITING

Behavioral Research Specialists, LLC

Glendale, California, 91206, United States

NOT YET RECRUITING

Sun Valley Research Center

Imperial, California, 92251, United States

NOT YET RECRUITING

CalNeuro Research Group

Los Angeles, California, 90025, United States

RECRUITING

ATP Clinical Research

Orange, California, 92866, United States

RECRUITING

NRC Research Institute

Orange, California, 92868, United States

RECRUITING

Inland Psychiatric Medical Group Inc (IPMG Research)

San Juan Capistrano, California, 92675, United States

NOT YET RECRUITING

Psychedelic Science Institute

Santa Monica, California, 90404, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

NOT YET RECRUITING

Yale School of Medicine - Yale Program for Psychedelic Science

New Haven, Connecticut, 06511, United States

RECRUITING

CNS Healthcare

Jacksonville, Florida, 32256, United States

RECRUITING

Accel Research Sites - Maitland

Maitland, Florida, 32751, United States

RECRUITING

Aqualane Clinical Research

Naples, Florida, 34105, United States

RECRUITING

Emory University Dept of Psychiatry and Behavioral Studies

Atlanta, Georgia, 30329, United States

NOT YET RECRUITING

Psych Atlanta

Marietta, Georgia, 30060, United States

RECRUITING

Rush University

Chicago, Illinois, 60612, United States

RECRUITING

Tandem Clinical Research

Marrero, Louisiana, 70006, United States

NOT YET RECRUITING

Johns Hopkins Medicine

Baltimore, Maryland, 21224, United States

NOT YET RECRUITING

Institute for Integrative Therapies

Eden Prairie, Minnesota, 55347, United States

RECRUITING

Bio Behavioral Health

Toms River, New Jersey, 08755, United States

RECRUITING

New York State Psychiatric Institute

New York, New York, 10032, United States

NOT YET RECRUITING

SP Research PLLC

Oklahoma City, Oklahoma, 73112, United States

NOT YET RECRUITING

Adams Clinical Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Flourish Research Philadelphia

Philadelphia, Pennsylvania, 19462, United States

RECRUITING

Austin Clinical Trial Partners

Austin, Texas, 78737, United States

NOT YET RECRUITING

North Texas Clinical Trials

Fort Worth, Texas, 76104, United States

NOT YET RECRUITING

Brain Health Consultants and TMS Center

Houston, Texas, 77046, United States

RECRUITING

Flourish Research San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Core Clinical Research

Everett, Washington, 98201, United States

NOT YET RECRUITING

Seattle Neuropsychiatric Treatment Center

Seattle, Washington, 98104, United States

RECRUITING

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

NOT YET RECRUITING

Thompson Brain & Mind Healthcare (TBMH)

Maroochydore, Queensland, 4558, Australia

RECRUITING

Ramsay Clinic

Melbourne, Victoria, 3004, Australia

RECRUITING

Neurocentrix Research

Melbourne, Victoria, 3053, Australia

RECRUITING

Monash University - Notting Hill

Notting Hill, Victoria, 3168, Australia

RECRUITING

Institute of neuropsychiatric Care (INEP)

Prague, Czechia

NOT YET RECRUITING

Psyon s.r.o.

Prague, Czechia

NOT YET RECRUITING

A-SHINE s.r.o.

Předměstí, Czechia

NOT YET RECRUITING

Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes

Homburg, Saarland, 66421, Germany

NOT YET RECRUITING

Charité Universitaetsmedizin Berlin

Berlin, 10117, Germany

NOT YET RECRUITING

University Hospital Frankfurt

Frankfurt am Main, 60528, Germany

NOT YET RECRUITING

Central Institute of Mental Health

Mannheim, 68159, Germany

NOT YET RECRUITING

Eginitio Hospital

Athens, 11528, Greece

RECRUITING

Attikon University Hospital

Athens, 12462, Greece

RECRUITING

Papageorgiou General Hospital

Thessaloniki, 56404, Greece

RECRUITING

Sheaf House - Tallaght Adult Mental Health Service

Dublin, D24 WK80, Ireland

RECRUITING

La Nua Day Hospital Mental Health Centre

Galway, H91 VE03, Ireland

RECRUITING

Uniwersytecki Szpital Kliniczny W Białymstoku

Bialystok, 15-272, Poland

NOT YET RECRUITING

Promente - Centrum Neurologii i Psychogeriatrii w Bydgoszczy

Bydgoszcz, 85-133, Poland

RECRUITING

UCK

Gdansk, 80-214, Poland

NOT YET RECRUITING

Centrum Badan Klinicznych PI-House Sp. z o.o

Gdansk, 80-546, Poland

NOT YET RECRUITING

MTZ Clinical Research Powered by Pratia

Warsaw, 02-172, Poland

NOT YET RECRUITING

Department of Pharmacology and Physiology of CNS

Warsaw, 02-957, Poland

NOT YET RECRUITING

Cambridge University Hospital NHS

Cambridge, CB1 2EU, United Kingdom

RECRUITING

Clerkenwell Health - Doncaster

Doncaster, DN4 8QN, United Kingdom

RECRUITING

NHS Research Scotland

Edinburgh, EH16 4TJ, United Kingdom

NOT YET RECRUITING

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

NOT YET RECRUITING

St Pancras Clinical Research

London, EC2Y 8EA, United Kingdom

NOT YET RECRUITING

King's College London

London, SE5 9RS, United Kingdom

RECRUITING

Clerkenwell Health - Welbeck Street

London, W1G 8DR, United Kingdom

RECRUITING

Re:Cognition Health

London, W1G9 RU, United Kingdom

RECRUITING

Clerkenwell Health - Baker Street

London, W1U 6RP, United Kingdom

RECRUITING

Wolfson Unit - Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust

Newcastle upon Tyne, NE4 6BE, United Kingdom

NOT YET RECRUITING

Ascend Clinical Research

Reading, RG7 8PA, United Kingdom

RECRUITING

Sheffield Health and Social Care NHS Foundation Trust

Sheffield, S4 7QQ, United Kingdom

NOT YET RECRUITING

Related Links

• Apply for Trial Here

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Felix Mazer

  Cybin IRL Limited

  STUDY DIRECTOR

Central Study Contacts

Clinical Development

CONTACT

877-361-4003; clinicaltrialsinfo@cybin.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 27, 2025
• Study Start: December 10, 2025
• Primary Completion (Estimated): March 18, 2027
• Study Completion (Estimated): May 8, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (3); GR (3); AU (5); US (32); GB (12); DE (4); IE (2); PL (6)