Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND) (EXTEND)
This open-label, Phase III long-term extension trial (n=468 estimated) assesses the safety and long-term efficacy of CYB003 in participants with MDD; participants may receive up to three 16 mg CYB003 medicine sessions ~3 weeks apart while continuing stable antidepressant therapy.
Detailed Description
EXTEND is a single-group long-term extension of the double-blind APPROACH and EMBRACE trials to evaluate safety and sustained efficacy of CYB003 (a deuterated psilocin analogue) in participants with major depressive disorder who previously participated in the parent studies.
Participants continue their stable antidepressant medication and receive psychological support; dosing consists of two medicine sessions ~3 weeks apart, with an optional third 16 mg dose if relapse occurs. Safety monitoring includes ECG and assessments for arrhythmia, suicidality evaluation (C-SSRS) and urine/breath drug/alcohol testing.
Planned enrolment is estimated at 468 across US sites; sponsor is Cybin IRL Limited.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
CYB003
experimentalSingle-group extension: eligible participants receive 16 mg CYB003 in two medicine sessions ~3 weeks apart; a single additional 16 mg dose permitted if relapse (max 3 doses). Participants continue stable antidepressant medication and receive psychological support.
Interventions
- Psilocybin16 mgvia Oral• up to three sessions (~3 weeks apart)• 3 doses total
Deuterated psilocin analog; initial 2 doses given ~3 weeks apart; optional third dose if relapse.
Participants
Inclusion Criteria
- 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 throughout the trial until 12 weeks after the participant's final dose of IP.
- Participants of childbearing potential who have a partner capable of producing sperm must agree to continue 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 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.
Exclusion Criteria
- 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.
Study Details
- StatusRecruiting
- PhasePhase III
- Typeinterventional
- DesignNon-randomized
- Target Enrollment468 participants
- TimelineStart: 2025-02-23End: 2027-09-06
- Compound
- Topic