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

Study Overview
=================
Brief 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).

Detailed 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.

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).

Conditions
-----------------
Healthy Volunteers, Major Depressive Disorder, Depression

Intervention / Treatment
-----------------
* Drug: ELE-101
* Drug: ELE-101 Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Part 1)<br>A single 10-minute intravenous infusion of 0.25 mg ELE-101 or placebo (randomized as 6 active and 2 placebo) | Drug: ELE-101<br>* ELE-101 solution for intravenous infusion<br>Drug: ELE-101 Placebo<br>* ELE-101 placebo matching solution for intravenous infusion<br>|
| Experimental: Cohort 2 (Part 1)<br>A single 10-minute intravenous infusion of 0.75 mg ELE-101 or placebo (randomized as 6 active and 2 placebo) | Drug: ELE-101<br>* ELE-101 solution for intravenous infusion<br>Drug: ELE-101 Placebo<br>* ELE-101 placebo matching solution for intravenous infusion<br>|
| Experimental: Cohort 3 (Part 1)<br>A single 10-minute intravenous infusion of 2.0 mg ELE-101 or placebo (randomized as 6 active and 2 placebo) | Drug: ELE-101<br>* ELE-101 solution for intravenous infusion<br>Drug: ELE-101 Placebo<br>* ELE-101 placebo matching solution for intravenous infusion<br>|
| Experimental: Cohort 4 (Part 1)<br>A single TBD minute intravenous infusion of TBD mg ELE-101 or placebo (randomized as 6 active and 2 placebo) | Drug: ELE-101<br>* ELE-101 solution for intravenous infusion<br>Drug: ELE-101 Placebo<br>* ELE-101 placebo matching solution for intravenous infusion<br>|
| Experimental: Cohort 5 (Part 1)<br>A single TBD minute intravenous infusion of TBD mg ELE-101 or placebo (randomized as 6 active and 2 placebo) | Drug: ELE-101<br>* ELE-101 solution for intravenous infusion<br>Drug: ELE-101 Placebo<br>* ELE-101 placebo matching solution for intravenous infusion<br>|
| Experimental: Cohort 6 (Part 2)<br>A single TBD minute intravenous infusion of TBD mg ELE-101 | Drug: ELE-101<br>* ELE-101 solution for intravenous infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ELE-101, psilocin, ELE-Psilo, psilocybin, psychedelic