Major Depressive DisorderPhase 3EXTENDNCT06605105
Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND)
A Phase 3 study testing CYB003 in people with Major Depressive Disorder, run by Cybin IRL Limited at 49 sites in 5 countries.
Trial summary
This is a long- term extension of the double-blind trials APPROACH (CYB003-002) and EMBRACE (CYB003-003). Its aim is to examine the safety and long-term efficacy of CYB003 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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 468 participants
- Where
- 49 sitesin 5 countries
- Study dates
- 18 Jul 2025to 6 Jun 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Has successfully completed either CYB003-002 APPROACH or CYB003-003 EMBRACE and received both dose administrations of trial medication
- Has continued the same antidepressant medication at the stable dose/day throughout CYB003-002 APPROACH or CYB003-003 EMBRACE
- Has provided written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form
- Participants capable of producing sperm must use a condom plus spermicide (where publicly available) during the trial and for 12 weeks after their final dose of IP, if their partner is a person of childbearing potential. In addition, their partner of childbearing potential must continue to use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) throughout the trial until 12 weeks after the participant's final dose of IP
- Participants of childbearing potential (POCBP) who have a partner capable of producing sperm must agree to continue to use a highly effective method of contraception (i.e., failure rate of less than 1% when used consistently and correctly) in combination with the use of a condom plus spermicide (where publicly available) during the trial and for 12 weeks after their final dose of IP
- Female participants must have a negative pregnancy test at Baseline (the end of trial [EOT] Visit in the APPROACH or EMBRACE trial), and prior to dose administration on the dosing day
Who cannot join
- newly developed symptoms of schizophrenia spectrum or other psychotic disorders that manifested in the APPROACH or EMBRACE trial
- Significant suicide risk as defined by suicidal ideation as endorsed on items 4 or 5 on the C-SSRS at Baseline OR has experienced an adverse event (AE) of suicide ideation/attempt or self-harm in CYB003-002 APPROACH OR has had a >1 point change in item 1 or 2 of the C-SSRS from Screening in CYB003-002 APPROACH
- Clinically relevant arrhythmia or vital sign changes noted during any of the dosing sessions in the APPROACH or EMBRACE trial
- Presence of clinically significant ECG abnormalities noted during the APPROACH or EMBRACE trials or at the Baseline of EXTEND
- Sensitivity or suspected sensitivity to CYB003 noted in the APPROACH or EMBRACE trial
- Positive urine test for drugs of abuse, or alcohol breath test prior to dosing.
- Unwilling to consent to audio and video recording of psychological support and dosing sessions
Trial locations and contacts
49 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
49 sites in 5 countries
United States42 sites
Cenexel iResearcvh Atlanta, LLC
Atlanta, Georgia, 30030
Atlanta Center For Medical Research
Atlanta, Georgia, 30331
Adams Clinical Boston
Boston, Massachusetts, 02116
Neurobehavioral Clinical Research
Canton, Ohio, 44720
Uptown Research Institute
Chicago, Illinois, 60640
Mountain View Clinical Research
Denver, Colorado, 80209
Adams Clinical Dallas
DeSoto, Texas, 75115
Cedar Clinical Research
Draper, Utah, 84020
Institute for Integrative Therapies
Eden Prairie, Minnesota, 55347
Starlight Clinical Research
Evergreen, Colorado, 80439
Behavioral Research Specialists, LLC
Glendale, California, 91206
Research Centers of America
Hollywood, Florida, 33024
Zillan Clinical Research
Houston, Texas, 77082
Clinical Neuroscience Solutions
Jacksonville, Florida, 32256
Kadima Neuropsychiatry Institute
La Jolla, California, 92037
K2 Medical Research
Lady Lake, Florida, 32159
Redbird Research
Las Vegas, Nevada, 89119
Segal Trials Center for Psychedelic Research
Lauderhill, Florida, 33319
TRIP Clinic and Psychedelic Science Institute
Los Angeles, California, 90004
CalNeuro Research Group
Los Angeles, California, 90025
Lipov Medical Group
Los Angeles, California, 90025
Accel Research Sites - Maitland
Maitland, Florida, 32751
K2 Medical Research
Maitland, Florida, 32751
Clinical Neuroscience Solutions, CNS Healthcare
Memphis, Tennessee, 38119
Adams Clinical Harlem
New York, New York, 10029
Excell Research, Inc
Oceanside, California, 92056
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
Global Medical Institutes, Princeton Medical Institute
Princeton, New Jersey, 08540
Sunstone Medical, PC
Rockville, Maryland, 20850
Open Mind Collective / UCSF Medical Center - Mount Zion
San Francisco, California, 94114
Inland Psychiatric Medical Group Inc (IPMG Research)
San Juan Capistrano, California, 92675
CenExel iResearch
Savannah, Georgia, 31405
Psychiatric Medicine Associates, LLC
Skokie, Illinois, 60076
Psychiatric Medicine Associates
Skokie, Illinois, 60076
Elixia Health
Springfield, Massachusetts, 01103
Adams Clinical Bronx
The Bronx, New York, 10461
Bio Behavioral Health
Toms River, New Jersey, 08755
Adams Clinical
Watertown, Massachusetts, 02472
Australia3 sites
Thompson Brain & Mind Healthcare
Maroochydore, Queensland, 4558
Ramsay Clinic
Melbourne, Victoria, 3004
Monash University - Notting Hill
Notting Hill, Victoria, 3168
Greece2 sites
Eginition Hospital, First Department of Psychiatry of the National and Kapodistrian University of Athens (NKUA)
Athens
Aristotle University of Tessaloniki
Thessaloniki
Poland1 site
Promente - Centrum Neurologii i Psychogeriatrii w Bydgoszczy
Bydgoszcz, 85-133
About this study
Official title: A Phase III Long-Term Extension Trial With Optional Additional Doses of CYB003 to Assess the Safety and Long-term Efficacy in Participants With Major Depressive Disorder (EXTEND)
This is a long- term extension of the double-blind trials APPROACH (CYB003-002) and EMBRACE (CYB003-003). Its aim is to examine the safety and long-term efficacy of CYB003 in participants with MDD.
- Conditions
- Major Depressive Disorder
- Being tested
- CYB003
- Keywords
- Major Depressive Disorder, MDD, Psilocybin, Psychedelic, CYB003, Depression, CYB003-002, Long-Term Extension, CYB003-003
- 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
| Study group | Role | What they receive |
|---|---|---|
| CYB003 | Experimental | Initial non-responders in CYB003-002 APPROACH and CYB003-003 EMBRACE, or initial responders who later relapse will be eligible to receive 16 mg of CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. If a participant relapses again, the participant may receive an additional single 16mg of CYB003 (maximum of 3 16mg doses in CYB003-004 EXTEND). Participants will continue on their current antidepressants and receive psychological support throughout the study. Receives: Drug: CYB003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg 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. The scale consists of ten items rated on a scale from 0 to 6, resulting in a total score ranging from 0 (normal / symptom absent) to 60 (severe depression).
Measured: Baseline, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168, Day 196, Day 244, Day 252, Day 280, Day 301; additional assessments at Day -15, Day -1, Day 2, Day 10, Day 17, Day 21, Day 23, Day 31, Day 42 if non-response or relapse criteria met
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2024
- Study start18 Jul 2025
- Primary completion6 Jun 2028 (estimated)
- Study completion6 Jun 2028 (estimated)
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 468 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cybin IRL Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Worldwide Clinical Trials
- Responsible party
- Sponsor
- Investigators
- Clinical Development, Study chair, Cybin IRL Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06605105
- Sponsor's protocol ID
- CYB003-004
- Acronym
- EXTEND
- Status last verified
- Sep 2026
- First submitted
- 16 Sep 2024
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Long-Term Extension Trial With Optional Additional Doses of CYB003 to Assess the Safety and Long-term Efficacy in Participants With Major Depressive Disorder (EXTEND)
- ClinicalTrials.gov ID
- NCT06605105
- Acronym / sponsor ID
- EXTEND / CYB003-004
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, MDD, Psilocybin, Psychedelic, CYB003, Depression, CYB003-002, Long-Term Extension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 468 participants (estimated)
- Lead sponsor
- Cybin IRL LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Worldwide Clinical Trials
- Study start
- 18 Jul 2025 (actual)
- Primary completion
- 6 Jun 2028 (estimated)
- Study completion
- 6 Jun 2028 (estimated)
- First posted
- 20 Sep 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.
This is a long- term extension of the double-blind trials APPROACH (CYB003-002) and EMBRACE (CYB003-003). Its aim is to examine the safety and long-term efficacy of CYB003 in participants with MDD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CYB003 | Experimental | Drug: CYB003Initial non-responders in CYB003-002 APPROACH and CYB003-003 EMBRACE, or initial responders who later relapse will be eligible to receive 16 mg of CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. If a participant relapses again, the participant may receive an additional single 16mg of CYB003 (maximum of 3 16mg doses in CYB003-004 EXTEND). Participants will continue on their current antidepressants and receive psychological support throughout the study. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Has successfully completed either CYB003-002 APPROACH or CYB003-003 EMBRACE and received both dose administrations of trial medication
- Has continued the same antidepressant medication at the stable dose/day throughout CYB003-002 APPROACH or CYB003-003 EMBRACE
- Has provided written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form
- Participants capable of producing sperm must use a condom plus spermicide (where publicly available) during the trial and for 12 weeks after their final dose of IP, if their partner is a person of childbearing potential. In addition, their partner of childbearing potential must continue to use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) throughout the trial until 12 weeks after the participant's final dose of IP
- Participants of childbearing potential (POCBP) who have a partner capable of producing sperm must agree to continue to use a highly effective method of contraception (i.e., failure rate of less than 1% when used consistently and correctly) in combination with the use of a condom plus spermicide (where publicly available) during the trial and for 12 weeks after their final dose of IP
Key exclusion criteria (7 listed)
- newly developed symptoms of schizophrenia spectrum or other psychotic disorders that manifested in the APPROACH or EMBRACE trial
- Significant suicide risk as defined by suicidal ideation as endorsed on items 4 or 5 on the C-SSRS at Baseline OR has experienced an adverse event (AE) of suicide ideation/attempt or self-harm in CYB003-002 APPROACH OR has had a >1 point change in item 1 or 2 of the C-SSRS from Screening in CYB003-002 APPROACH
- Clinically relevant arrhythmia or vital sign changes noted during any of the dosing sessions in the APPROACH or EMBRACE trial
- Presence of clinically significant ECG abnormalities noted during the APPROACH or EMBRACE trials or at the Baseline of EXTEND
- Sensitivity or suspected sensitivity to CYB003 noted in the APPROACH or EMBRACE trial
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 | CYB003 |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Baseline, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168, Day 196, Day 244, Day 252, Day 280, Day 301; additional assessments at Day -15, Day -1, Day 2, Day 10, Day 17, Day 21, Day 23, Day 31, Day 42 if non-response or relapse criteria met
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. The scale consists of ten items rated on a scale from 0 to 6, resulting in a total score ranging from 0 (normal / symptom absent) to 60 (severe depression).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 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.
Clinical Development study chair
Cybin IRL Limited
49 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CYB003 in people with Major Depressive Disorder, run by Cybin IRL Limited at 49 sites in 5 countries.
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 6 inclusion and 7 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: enrolling by invitation, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, Australia, Greece, Poland, United Kingdom. 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. 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?
This study is still under way. Results are not available in the source record yet.
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-Asberg Depression Rating Scale (MADRS) (time frame: Baseline, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168, Day 196, Day 244, Day 252, Day 280, Day 301; additional assessments at Day -15, Day -1, Day 2, Day 10, Day 17, Day 21, Day 23, Day 31, Day 42 if non-response or relapse criteria met). 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 25 Sep 2026.