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

March 9, 2026 updated by: Cybin IRL Limited

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

468

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85022
        • Combined Research Orlando
    • California
      • San Francisco, California, United States, 94114
        • Open Mind Collective / UCSF Medical Center - Mount Zion
    • Colorado
      • Denver, Colorado, United States, 80209
        • Mountain View Clinical Research
      • Evergreen, Colorado, United States, 80439
        • Starlight Clinical Research
    • Florida
      • Hollywood, Florida, United States, 33024
        • Research Centers of America
      • Lady Lake, Florida, United States, 32159
        • K2 Medical Research
      • Lauderhill, Florida, United States, 33319
        • Segal Trials Center for Psychedelic Research
      • Orlando, Florida, United States, 32801
        • Clinical Neuroscience Solutions, Inc
    • Georgia
      • Atlanta, Georgia, United States, 30331
        • Atlanta Center for Medical Research
      • Atlanta, Georgia, United States, 30030
        • Cenexel iResearcvh Atlanta, LLC
      • Savannah, Georgia, United States, 31405
        • CenExel iResearch
    • Illinois
      • Chicago, Illinois, United States, 60640
        • Uptown Research Institute
      • Skokie, Illinois, United States, 60076
        • Psychiatric Medicine Associates, LLC
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Sunstone Medical, PC
    • Massachusetts
      • Boston, Massachusetts, United States, 02116
        • Adams Clinical Boston
      • Watertown, Massachusetts, United States, 02472
        • Adams Clinical
    • Ohio
      • Canton, Ohio, United States, 44720
        • Neurobehavioral Clinical Research
    • Texas
      • DeSoto, Texas, United States, 75115
        • InSite Clinical Research, LLC
    • Utah
      • Draper, Utah, United States, 84020
        • Cedar Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: CYB003
CYB003 is a deuterated psilocin analog

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cybin IRL Limited

Collaborators

Worldwide Clinical Trials

Investigators

  • Study Chair: Clinical Development, Cybin IRL Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 18, 2025

Primary Completion (Estimated)

March 15, 2028

Study Completion (Estimated)

March 15, 2028

Study Registration Dates

First Submitted

September 16, 2024

First Submitted That Met QC Criteria

September 17, 2024

First Posted (Actual)

September 20, 2024

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 9, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CYB003-004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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