Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND)

Phase 3

Not yet recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: CYB003

• Registration Number: NCT06605105
• Lead Sponsor: Cybin IRL Limited

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-16
• Study First Submitted QC: 2024-09-17
• Study First Posted: 2024-09-20
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-08
• Study Start: 2025-07-15
• Primary Completion: 2028-03-15
• Study Completion: 2028-03-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 468

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 (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

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CYB003	CYB003	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.

Primary Outcome Measures

Name	Time	Method
Montgomery-Asberg Depression Rating Scale (MADRS)	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).