Major Depressive DisorderPhase 3APPROACHNCT06564818
"A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder"
A Phase 3 study testing CYB003 and Psychological Support in people with Major Depressive Disorder, run by Cybin IRL Limited at 45 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- CYB003 and Psychological Support
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 223 participants
- Where
- 45 sitesUnited States
- Study dates
- 17 Dec 2024to 23 Oct 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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, neurological, cardiovascular, respiratory, gastrointestinal [including dyspepsia or gastroesophageal reflux disease], hepatic, or renal disorder).
- Participants with renal insufficiency.
- 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 or blood pressure
- History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the trial medication.
- Participant has a presence or relevant history of organic brain disorders (e.g., epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmal disease, brain tumor or other medical conditions associated with seizures or convulsions).
- Known sensitivity to psilocin and/or any excipients present in the formulation.
- Participant is taking or has taken OTC doses of 5-HTP or St John's Wort within 14 days prior to trial medication administration.
- The participant has participated in a clinical trial and has received a medication or a new chemical entity within 12 weeks prior to dosing with the current trial medication. Participants who have completed observational or non-interventional studies will be allowed.
- 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.
- Staff and family members of Cybin IRL Limited, investigator sites, contract research organization or other vendors.
Trial locations and contacts
45 sites in 1 country.
45 sites in 1 country
United States45 sites
Atlanta Center for Medical Research, CenExel
Atlanta, Georgia, 30331
CenExel CIT (Clinical Innovations, Inc)
Bellflower, California, 90706
Adams Clinical Boston
Boston, Massachusetts, 02116
Adams Clinical
Boston, Massachusetts, 02472
Great Lakes Clinical Trials, DBA Flourish Research
Chicago, Illinois, 60640
Uptown Research Institute
Chicago, Illinois, 60640
CenExel iResearch Atlanta
Decatur, Georgia, 30330
Mountain View Clinical Research
Denver, Colorado, 80209
InSite Clinical Research, LLC
DeSota, Texas, 75115
Starlight Clinical Research
Evergreen, Colorado, 80439
Research Centers of America
Hollywood, Florida, 33024
Zillan Clinical Research
Houston, Texas, 77433
Kadima Neuropsychiatry Institute
La Jolla, California, 92037
Redbird Research, LLC
Las Vegas, Nevada, 89119
Oasis Clinical Trials
Las Vegas, Nevada, 89121
Bespoke Treatment/Lipov Medical Group
Los Angeles, California, 90025
K2 Medical Research-Maitland
Maitland, Florida, 32751
Clinical Neuroscience Solutions, CNS Healthcare
Memphis, Tennessee, 38119
Floridian Neuroscience Institute
Miami, Florida, 33135
Monroe Biomedical Research
Monroe, North Carolina, 28112
Catalina Research Institute
Montclair, California, 91763
Cedar Clinical Research
Murray, Utah, 84107
DelRicht Research
New Orleans, Louisiana, 70115
Adams Clinical Harlem
New York, New York, 100029
Neurobehavioral Clinical Research
North Canton, Ohio, 44720
Segal Trials West Broward
North Miami, Florida, 33161
Excell Research, Inc
Oceanside, California, 92056
Inner Space Research, LLC
Orem, Utah, 84058
Clinical Neuroscience Solutions, Inc
Orlando, Florida, 32801
Charter Research
Orlando, Florida, 32803
Combined Research Orlando Phase I-IV
Orlando, Florida, 32807
Adams Clinical Philadelphia
Philadelphia, Pennsylvania, 19104
Scottsdale Research Institute
Phoenix, Arizona, 85022
Mountain Clinical Trials
Phoenix, Arizona, 85050
Global Medical Institutes, Princeton Medical Institute
Princeton, New Jersey, 08540
Sunstone Medical, PC
Rockville, Maryland, 20850
Open Mind Therapeutics
San Francisco, California, 94114
Inland Psychiatric Medical Group Inc
San Juan Capistrano, California, 92675
CenExel iResearch Savannah
Savannah, Georgia, 31405
Psychiatric Medicine Associates, LLC
Skokie, Illinois, 60076
Elixia Health
Springfield, Massachusetts, 01103
K2 Medical Research - Tampa
Tampa, Florida, 33634
Adams Clinical Bronx
The Bronx, New York, 10461
Noble Clinical Research
Tucson, Arizona, 85704
Del Sol Research Management
Tucson, Arizona, 85715
About this study
Official title: 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
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.
- Conditions
- Major Depressive Disorder
- Being tested
- CYB003, Psychological Support, Placebo
- Keywords
- Major Depressive Disorder, MDD, Psilocybin, Psychedelic, Psilocin, CYB003, CYB003-001, Depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYB003Drug
CYB003 is a Deuterated Psilocin Analog.
Psychological SupportBehavioural
Manualized psychological support performed by facilitators
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: CYB003; Behavioral: Psychological Support |
| 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. Receives: Behavioral: Psychological Support; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Åsberg Depression Rating Scale (MADRS)
The MADRS is a 10-item scale with ratings based on a clinical interview which moves from broadly phrased questions about symptoms to more detailed ones allowing a precise rating of severity.
Measured: Screening Day-45, Baseline Day-1, Day 2, Day 10, Day 21, Day 23, Day 31, and Day 42 (End of Treatment)
Secondary outcomes (4)
The Beck Depression Inventory-Second Edition (BDI-II)
The Beck Depression Inventory-Second Edition (BDI-II) is a 21-question multiple-choice self-report inventory, assessing depressive symptoms and severity.
Measured: Baseline Day-1, Day 21, and Day 42 (End of Treatment)
The Clinical Global Impression Scale (CGI-S)
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 and global improvement measures will be utilized for this trial.
Measured: Screening Day-45, Baseline Day-1, and Day 42 (End of Treatment)
The Generalized Anxiety Disorder 7-item scale (GAD-7)
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.
Measured: 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)
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 into 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.
Measured: Baseline Day-1, Day 21, and Day 42 (End of Treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2024
- Study start17 Dec 2024
- Primary completion4 Sep 2026
- Study completion23 Oct 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 223 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cybin IRL Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Development, Study chair, Cybin IRL Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06564818
- Sponsor's protocol ID
- CYB003-002
- Acronym
- APPROACH
- Status last verified
- Sep 2026
- First submitted
- 20 Aug 2024
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06564818
- Acronym / sponsor ID
- APPROACH / CYB003-002
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, MDD, Psilocybin, Psychedelic, Psilocin, CYB003, CYB003-001, Depression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 223 participants (actual)
- Lead sponsor
- Cybin IRL LimitedIndustry (pharma, biotech, devices)
- Study start
- 17 Dec 2024 (actual)
- Primary completion
- 4 Sep 2026 (actual)
- Study completion
- 23 Oct 2026 (actual)
- First posted
- 21 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm A: CYB003 in 2 of 2 Dosing Sessions | Experimental | Drug: CYB003, Behavioral: Psychological SupportArm 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 | Behavioral: Psychological Support, Drug: PlaceboArm 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYB003CYB003 is a Deuterated Psilocin Analog. | Drug | Experimental Arm A: CYB003 in 2 of 2 Dosing Sessions |
| Psychological SupportManualized psychological support performed by facilitators | Behavioural | Experimental Arm A: CYB003 in 2 of 2 Dosing Sessions, Placebo Comparator Arm B: Placebo in 2 of 2 Dosing Sessions |
| PlaceboPlacebo | Drug | Placebo Comparator Arm B: Placebo in 2 of 2 Dosing Sessions |
Primary outcome
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: Screening Day-45, Baseline Day-1, Day 2, Day 10, Day 21, Day 23, Day 31, and Day 42 (End of Treatment)
The MADRS is a 10-item scale with ratings based on a clinical interview which moves from broadly phrased questions about symptoms to more detailed ones allowing a precise rating of severity.
4 secondary outcomes
The Beck Depression Inventory-Second Edition (BDI-II)
Time frame: Baseline Day-1, Day 21, and Day 42 (End of Treatment)
The Clinical Global Impression Scale (CGI-S)
Time frame: Screening Day-45, Baseline Day-1, and Day 42 (End of Treatment)
The Generalized Anxiety Disorder 7-item scale (GAD-7)
Time frame: 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)
Time frame: Baseline Day-1, Day 21, and Day 42 (End of Treatment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Development study chair
Cybin IRL Limited
45 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CYB003 and Psychological Support in people with Major Depressive Disorder, run by Cybin IRL Limited at 45 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Åsberg Depression Rating Scale (MADRS) (time frame: Screening Day-45, Baseline Day-1, Day 2, Day 10, Day 21, Day 23, Day 31, and Day 42 (End of Treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.