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

NCT06605105 | Enrolling By Invitation Phase 3 FDA Drug

• 1 other identifier: CYB003-004
• Study Type: interventional
• Target: 468
• Locations: 1 country
• Sites: 19

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.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; MDD; Psilocybin; Psychedelic; CYB003; Depression; CYB003-002; Long-Term Extension; CYB003-003

Outcome Measures

Primary Outcomes (1)

• 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).

  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

Study Arms (1)

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.

Drug: CYB003

Interventions

CYB003 DRUG

CYB003 is a deuterated psilocin analog

CYB003

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (19)

Combined Research Orlando

Phoenix, Arizona, 85022, United States

Location

Open Mind Collective / UCSF Medical Center - Mount Zion

San Francisco, California, 94114, United States

Location

Mountain View Clinical Research

Denver, Colorado, 80209, United States

Location

Starlight Clinical Research

Evergreen, Colorado, 80439, United States

Location

Research Centers of America

Hollywood, Florida, 33024, United States

Location

K2 Medical Research

Lady Lake, Florida, 32159, United States

Location

Segal Trials Center for Psychedelic Research

Lauderhill, Florida, 33319, United States

Location

Clinical Neuroscience Solutions, Inc

Orlando, Florida, 32801, United States

Location

Cenexel iResearcvh Atlanta, LLC

Atlanta, Georgia, 30030, United States

Location

Atlanta Center For Medical Research

Atlanta, Georgia, 30331, United States

Location

CenExel iResearch

Savannah, Georgia, 31405, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

Psychiatric Medicine Associates, LLC

Skokie, Illinois, 60076, United States

Location

Sunstone Medical, PC

Rockville, Maryland, 20850, United States

Location

Adams Clinical Boston

Boston, Massachusetts, 02116, United States

Location

Adams Clinical

Watertown, Massachusetts, 02472, United States

Location

Neurobehavioral Clinical Research

Canton, Ohio, 44720, United States

Location

InSite Clinical Research, LLC

DeSoto, Texas, 75115, United States

Location

Cedar Clinical Research

Draper, Utah, 84020, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Development

  Cybin IRL Limited

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 20, 2024
• Study Start: July 18, 2025
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): March 15, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)