ELE-101 Safety & Tolerability Study in Healthy Participants and Patients With Depression

Depression Clinical Trial

Official title:

A Phase I, Randomised, Double-Blind, Placebo-Controlled Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Intravenous Doses of ELE-101 in Healthy Adult Participants (Part 1) and A Phase IIa, Open-Label Study to Evaluate a Range of Pharmacodynamic Effects of a Single Intravenous Dose of ELE-101 in Patients With Major Depressive Disorder (Part 2).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05434156
• Other study ID #: ET1001-ELE-101
• Secondary ID: 2022-000150-29
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 27, 2022
• Est. completion date: September 2024

Study information

• Verified date: January 2024
• Source: Eleusis Therapeutics
• Contact: Beckley Psytech Ltd
• Phone: +44 (0)1865 987633
• Email: Medinfo[@]beckleypsytech.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to assess the safety and tolerability of a drug called ELE-101 and see how the body absorbs and removes the drug and how it affects the body in healthy adult participants (Part 1) and in patients with depression (Part 2).

Description:

This is a 2-part study. Part 1 is a phase I, double-blind, placebo-controlled, randomized study to assess the safety, tolerability, pharmacokinetic (PK) profile, pharmacodynamic (PD) and subjective drug intensity (SDI) of single ascending intravenous (IV) doses of ELE-101 in healthy male and female adult participants. Part 2 is a Phase IIa, open-label study to evaluate a range of pharmacodynamic effects of a single intravenous dose of ELE-101 in patients with depression. Healthy participants will receive either ELE-101 or placebo as an IV infusion in Part 1 and patients with MDD will receive ELE-101 as an IV infusion in Part 2.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: September 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Healthy male or female participants aged 18 to 65 years, inclusive.
• Participants have a body mass index (BMI) of 18 to 35 kg/m2, inclusive.
• Participants are able and willing to give written informed consent, adhere to the compliance terms during participation in the study, undergo the examinations and testing set forth in the study Protocol and clearly and reliably communicate their subjective symptoms to the Investigator.
• Part 2 Only: Patient has a diagnosis of MDD and is not on antidepressant medication.

Exclusion Criteria:

• Current, or history (within the last 6 months) of, alcohol or substance use disorder.
• Use of pharmacological compounds for psychiatric or neurological conditions acting on the CNS within 30 days or 5 half-lives (whichever is longer) prior to Screening.
• Current or clinically relevant history of schizophrenia, psychotic, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder or panic disorder.
• In first-degree relatives, a history of schizophrenia, psychosis, bipolar disorder, delusional disorder, paranoid personality disorder or schizoaffective disorder.
• History of a diagnosis of Hallucinogen Persistent Perceptual Disorder (HPPD).
• Significant suicide risk.
• Other personal circumstances and behavior that is incompatible with establishment of rapport or safe exposure to psilocin, as judged by the Investigator.
• Part 1 Only: Ongoing current MDD, or history of MDD within the last year.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Healthy Volunteers
• Major Depressive Disorder

Intervention

Drug:
• ELE-101
ELE-101 solution for intravenous infusion
• ELE-101 Placebo
ELE-101 placebo matching solution for intravenous infusion

Locations

Country	Name	City	State
United Kingdom	MAC Clinical Research	Liverpool
United Kingdom	MAC Clinical Research	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Eleusis Therapeutics

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of participants with at least one safety event	Safety will be evaluated by the monitoring of adverse events (AEs), vital signs, blood pressure, heart rate, pulse oximetry, electrocardiogram (ECG) evaluations, clinical laboratory assessments, injection site reactions and physical examination findings.; Suicidal ideation and behavior will be evaluated using the Columbia-Suicide Severity Rating Scale (C-SSRS).; Percentage of participants who experience at least one treatment-emergent adverse event (TEAE) will be captured.; Tolerability will be measured using the SDI questionnaires to rate the intensity of the psychedelic experience alongside recordings of anticipated adverse effects such as nausea and headache.	Baseline up to Day 8
Primary	Part 2: Subjective Drug Intensity Ratings	- The SDI questionnaire will be used to rate the real-time intensity of the psychedelic experience	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: Cmax: Maximum observed plasma concentration for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: Tmax: Time to reach maximum plasma concentration (Cmax) for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: AUCinf: Area under the plasma concentration-time curve from Time 0 to Infinity for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: AUClast: Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: AUC0-24: Area under the plasma concentration-time curve from Time 0 to 24 hours for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: VZ: volume of distribution during the terminal disposition phase for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: VZss: volume of distribution at steady state for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: Cl: apparent total clearance from plasma for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: MRTinf: mean residence time from Time 0 to Infinity for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: t1/2: Terminal disposition phase half-life for ELE-101 and its metabolites	PK parameters in plasma will be calculated for psilocin and its primary metabolites throughout the study	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 1 and 2: Dischargeability: Assessment of subject-discharge readiness	The dischargeability evaluation will be based on Investigator judgement after review of participant safety data.	post-dose and 24 hours post-dose
Secondary	Part 1: The dose related psychoactive effects of ELE-101 as evaluated by a Visual Analogue Scale	The Subjective Drug Intensity (SDI) is a Visual Analogue Scale scored from 0-10.	pre-dose and at multiple time-points up to 24 hours post-dose
Secondary	Part 2: The effects of ELE-101 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS)	The MADRS is a diagnostic questionnaire with ten items for measuring the severity of depressive episodes in patients with mood disorders. A higher MADRS score indicates more severe depression, and each item is scored from 0 to 6. The overall score ranges from 0 to 60.	Baseline up to Day 29
Secondary	Part 2: Percentage of participants with at least one safety event	Safety will be evaluated by the monitoring of adverse events (AEs), vital signs, blood pressure, heart rate, pulse oximetry, electrocardiogram (ECG) evaluations, clinical laboratory assessments, injection site reactions and physical examination findings.; Suicidal ideation and behavior will be evaluated using the Columbia-Suicide Severity Rating Scale (C-SSRS).; Percentage of participants who experience at least one treatment-emergent adverse event (TEAE) will be captured.; Tolerability will be measured using the SDI questionnaires to rate the intensity of the psychedelic experience alongside recordings of anticipated adverse effects such as nausea and headache.	Baseline up to Day 29