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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cybin IRL Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-02-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516805-22-00

ClinicalTrials.gov

NCT06605105

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety

To assess durability of response to IP after initial randomized, double-blind treatment.

Secondary objectives 2

1. To assess the proportion of participants who require either 2 or 3 additional doses of IP during the EXTEND trial. (key secondary)
2. To further assess the long-term efficacy of IP

Conditions and MedDRA coding

Major Depressive Disorder

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant has successfully completed either the APPROACH or EMBRACE trial and received BOTH dose administrations of trial medication.
2. Participant has continued the same antidepressant medication at the stable dose/day throughout the 12-week APPROACH or EMBRACE trial.
3. If the participant was engaged in a psychotherapeutic relationship in the APPROACH or EMBRACE trial, they agree to remain in stable and consistent therapy for the remainder of the trial with no changes in the frequency or the setting throughout the trial.
4. Participants can refrain from nicotine use during the dosing session (up to 8 hours).
5. 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.
6. 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.
7. 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.
8. Postmenopausal status will not be confirmed with follicle-stimulating hormone (FSH) levels. Therefore, participants who may have become post menopausal in the preceding trial but the status was unable to be confirmed, must be willing to continue with the contraception requirements
9. Participant has provided written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).

Exclusion criteria 22

1. Any concern by the Principal Investigator that a participant may have undiagnosed or newly developed symptoms of schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder, brief psychotic disorder, attention deficit hyperactivity disorder, bipolar disorder, or borderline personality disorder that manifested in the APPROACH or EMBRACE trial.
2. New awareness of a participant’s family member being diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first-degree relatives) since Screening in the APPROACH or EMBRACE trial.
3. Significant suicide risk as defined by (a) suicidal ideation as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C SSRS) at the Baseline of EXTEND (the EOT Visit in the APPROACH or EMBRACE trial), (b) participants have experienced an adverse event of suicidal ideation/attempt or self-harm in the APPROACH or EMBRACE trial, (c) have had a >1 point change in item 1 or 2 of the C SSRS performed at the EOT Visit in the APPROACH or EMBRACE trial, compared to their score on these items from the Screening Visit of the APPROACH or EMBRACE trial
4. Use of a prescription medicine other than a stable chronic dose of antidepressant medication, except those permitted during the APPROACH or EMBRACE trial or approved by a Medical Monitor
5. Development of clinically relevant abnormal physical health condition or need of treatment for a condition that could interfere with the trial or pose an unacceptable risk to the participant in this trial as judged by the Investigator (including but not limited to neurological, cardiovascular, respiratory, gastrointestinal [including dyspepsia or gastroesophageal reflux disease], hepatic or renal disorder).
6. Participants with renal insufficiency (eGFR ≤59 mL/min/1.73 m2).
7. Participants with stable hypothyroidism or hyperthyroidism, at Screening in the APPROACH or EMBRACE trial that are unable to continue appropriate medication until the final visit in the EXTEND trial.
8. Clinically relevant arrhythmia or vital sign changes noted during any of the dosing sessions in the APPROACH or EMBRACE trial.
9. Current diagnosis of uncontrolled hypertension or an arrhythmia, or clinically abnormal results for heart rate (resting supine heart rate >100 beats per minute) or blood pressure (BP) (resting supine systolic BP >139 mmHg or resting supine diastolic BP >89 mmHg) at Baseline (EOT of APPROACH/EMBRACE). Participants with well controlled hypertension and who have been on stable dose/doses of either 1 or 2 allowable antihypertensive medications for ≥4 weeks prior to Baseline are permitted.
10. QT interval corrected for heart rate using Fridericia’s formula >450 msec for males and >470 msec for females following triplicate ECG readings at the Baseline of EXTEND (the EOT Visit in the APPROACH or EMBRACE trial).
11. Presence of clinically significant ECG abnormalities noted during the APPROACH or EMBRACE trials or at the Baseline of EXTEND (the EOT Visit in the APPROACH or EMBRACE trial) as defined by Investigator judgment
12. Clinical evidence of any new disease and/or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the IP.
13. Participant has experienced any new onset organic brain disorders (e.g., epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmal disease, brain tumor) or other medical condition associated with seizure or convulsion risk since Screening in the APPROACH or EMBRACE trial.
14. Safety laboratory values at the Baseline of EXTEND (the EOT Visit in the APPROACH or EMBRACE trial) for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) or total bilirubin (TBil) levels ≥1.5 × the upper limit of normal (ULN). These laboratory evaluations may be repeated once at the discretion of the Investigator. If the repeat test is within the reference range, the participant may be included only if the Investigator considers that the previous finding will not introduce additional risk factors and will not interfere with interpretation of safety data
15. Participants that do not agree to abstain from drugs of abuse for the entire trial and/or do not agree to refrain from alcohol use from 48 hours before each scheduled visit until discharge from the trial site
16. Sensitivity or suspected sensitivity to IP noted in the APPROACH or EMBRACE trial
17. Participants that are unable to abstain from strenuous exercise within 48 hours before each clinic visit. Other eligibility considerations (e.g., participant personal circumstances, behavior, and/or any current problem or future plans that might interfere with participation or that is incompatible with establishment of rapport or safe exposure to psilocin), as judged by the Investigator
18. Participants capable of producing sperm that are unable to abstain from sperm donation until 12 weeks after final dosing.
19. Participants of childbearing potential who have a positive urine test and, subsequently, confirmatory serum pregnancy test at the Baseline (the EOT Visit in the APPROACH or EMBRACE trial), OR any time in the trial, OR planning to conceive, OR unwilling to abstain from egg (ova) donation until 12 weeks after final dosing
20. Any concern that participants may be at risk of developing serotonin syndrome with dosing of IP in the EXTEND trial
21. Participant is unwilling to consent to audio and video recording of psychological support and dosing sessions
22. Investigator’s decision that, for any reason, a participant may be unsuitable for enrollment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first relapse from Baseline of EXTEND trial in participants who have had a stable response in either the APPROACH or EMBRACE trial

Secondary endpoints 6

1. Percentage of participants who are either responders or non-responders in APPROACH or EMBRACE and require 2 additional doses of IP in EXTEND.
2. Percentage of participants who are either responders or non-responders in APPROACH or EMBRACE and require 3 additional doses of IP in EXTEND.
3. Percentage of participants with sustained response defined as absence of a relapse after administration of 2 doses of IP in APPROACH or EMBRACE to the endpoint of EXTEND with 1 increase in MADRS total score above 50% decrease in MADRS total score permitted.
4. Percentage of participants with sustained remission defined as MADRS total score ≤10 after administration of 2 doses of IP in APPROACH or EMBRACE to the endpoint of EXTEND with 1 increase in MADRS total score >10 permitted.
5. Percentage of responders and remitters to 2 doses of IP administered in EXTEND who later relapse.
6. Change from Baseline to last visit in the total MADRS score in participants who did not respond to IP in APPROACH or EMBRACE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cybin IRL Limited

Sponsor organisation

Cybin IRL Limited

Address

One Spencer Dock, North Wall Quay North Wall Quay

City

Dublin 1

Postcode

DO1 X9R7

Country

Ireland

Scientific contact point

Organisation

Cybin IRL Limited

Contact name

Atul Mahableshwarkar, MD SVP, Clinical Development

Public contact point

Organisation

Cybin IRL Limited

Contact name

Stephen Gorny, Director, Clinical Operations

Third parties 13

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications