A Study of CLE-100 (Oral Esketamine) in Addition to Standard Antidepressant Drug for Major Depressive Disorder - CLEO Study

November 14, 2023 updated by: Clexio Biosciences Ltd.

A Two-Part Study of CLE-100 as an Adjunct Therapy in Subjects With Major Depressive Disorder

The clinical trial is a Phase 2, double-blind, randomized, placebo controlled study in Major Depressive Disorder (MDD) participants currently treated with antidepressant therapy. The objective of the study is to assess CLE-100 for the treatment of MDD in participants currently treated with standard antidepressant therapy.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

CLEO study is performed in two parts (part A and Part B). The sponsor is currently recruiting only for the Part B of the study.

Part A will be an inpatient study to assess the safety, tolerability, and pharmacokinetics of CLE-100 (oral esketamine) in MDD participants currently treated with an antidepressant drug. It will include a screening phase (up to 35 days), a 1 week inpatient double-blind treatment phase and an outpatient post treatment safety follow-up phase of 1 week after last study drug administration.

Part B will be a study to assess the safety and efficacy of CLE-100 (oral esketamine) in MDD participants currently treated with an antidepressant drug with inadequate response to standard antidepressant therapy.

The participants will remain on their current antidepressant therapy with no dose change during the study.

Study Type

Interventional

Enrollment (Actual)

130

Phase

  • Phase 2

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

      • San Juan, Puerto Rico, 00918
        • Clinical Site 150
    • Arkansas
      • Bentonville, Arkansas, United States, 72712
        • Clinical Site 126
      • Little Rock, Arkansas, United States, 72209
        • Clinical Site 120
      • Little Rock, Arkansas, United States, 72209
        • Clinical Site 129
    • California
      • Anaheim, California, United States, 92805
        • Clinical Site 141
      • Bellflower, California, United States, 90706
        • Clinical Site 115
      • Lafayette, California, United States, 94549
        • Clinical Site 132
      • Oakland, California, United States, 94607
        • Clinical Site 117
      • Oceanside, California, United States, 92056
        • Clinical Site 113
      • Riverside, California, United States, 92506
        • Clinical Site 123
      • Santa Ana, California, United States, 92705
        • Clinical Site 124
      • Santa Rosa, California, United States, 95401
        • Clinical Site 142
      • Torrance, California, United States, 90502
        • Clinical Site 112
    • Colorado
      • Denver, Colorado, United States, 80209
        • Clinical Site 145
    • Florida
      • Hialeah, Florida, United States, 33016
        • Clinical Site 107
      • Miami, Florida, United States, 33145
        • Clinical Site 116
      • Miami Gardens, Florida, United States, 33014
        • Clinical Site 108
      • Orlando, Florida, United States, 32803
        • Clinical Site 105
      • Orlando, Florida, United States, 32807
        • Clinical Site 137
    • Georgia
      • Atlanta, Georgia, United States, 30338
        • Clinical Site 140
      • Decatur, Georgia, United States, 30030
        • Clinical Site 104
      • Marietta, Georgia, United States, 30060
        • Clinical Site 122
    • Maryland
      • Baltimore, Maryland, United States, 21208
        • Clinical Site 131
      • Rockville, Maryland, United States, 20877
        • Clinical Site 136
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Clinical Site 103
      • Boston, Massachusetts, United States, 02131
        • Clinical Site 121
    • Michigan
      • Dearborn Heights, Michigan, United States, 48034
        • Clinical Site 151
    • Missouri
      • Saint Louis, Missouri, United States, 63128
        • Clinical Site 139
    • Nebraska
      • Lincoln, Nebraska, United States, 68526
        • Clinical Site 125
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Clinical Site 110
    • New Jersey
      • Marlton, New Jersey, United States, 08053
        • Clinical Site 101
      • Toms River, New Jersey, United States, 08755
        • Clinical Site 148
    • New York
      • New York, New York, United States, 10036
        • Clinical Site 128
      • Staten Island, New York, United States, 10312
        • Clinical Site 102
    • North Carolina
      • Hickory, North Carolina, United States, 28601
        • Clinical Site 111
      • Raleigh, North Carolina, United States, 27609
        • Clinical Site 143
    • Ohio
      • Middleburg Heights, Ohio, United States, 44130
        • Clinical Site 138
      • North Canton, Ohio, United States, 44720
        • Clinical Site 127
    • Pennsylvania
      • Media, Pennsylvania, United States, 19063
        • Clinical Site 106
      • Philadelphia, Pennsylvania, United States, 19104
        • Clinical Site 118
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Clinical Site 114
      • Houston, Texas, United States, 77030
        • Clinical Site 109
      • Missouri City, Texas, United States, 88459
        • Clinical Site 149
      • Plano, Texas, United States, 75093
        • Clinical Site 144
    • Utah
      • Draper, Utah, United States, 84020
        • Clinical Site 147
    • Washington
      • Bellevue, Washington, United States, 98007
        • Clinical Site 135

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Part A - Inclusion Criteria:

  1. Male or female between 18 to 60 years of age
  2. Primary diagnosis of MDD, without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
  3. MADRS score of at least 18 at Screening
  4. Treatment with stable dose of the current antidepressant therapy for at least 4 weeks for the current major depressive episode (MDE)
  5. Body mass index (BMI) between 18 and 40 kg/m2, inclusive
  6. Is able and competent to read and sign the informed consent form (ICF).

Part A - Exclusion Criteria:

  1. History of substance use disorder per DSM-5 criteria, except for tobacco use disorder
  2. History or current diagnosis of bipolar disorder, schizophrenia, schizoaffective disorders, binge eating disorder dementia, delirium, amnesia, or any other significant cognitive disorder
  3. Posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders)
  4. Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk
  5. Female of childbearing potential without appropriate contraceptive means, pregnant or breastfeeding

Part B - Inclusion Criteria:

  1. Male or female between 18 to 65 years of age
  2. Primary diagnosis of MDD without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
  3. MADRS score of at least 24 at Screening.
  4. At least 2 inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE)
  5. Current MDE for at least 12 weeks
  6. BMI between 18 and 40 kg/m2, inclusive.
  7. Is able and competent to read and sign the ICF.

Part B - Exclusion Criteria:

  1. Inadequate response to more than 5 treatment courses of antidepressant medication therapy during the current MDE
  2. Current MDE for longer than 5 years.
  3. 3. Has a current substance use disorder or history of any substance use disorder per DSM-5 criteria within 12 months prior to Screening, except for tobacco use disorder.
  4. Has a history or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorders.
  5. Has dementia, delirium, amnesia, or any other significant cognitive disorder.
  6. Has posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders, eating disorders, etc.).
  7. Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk.
  8. Has been randomized in Part A of this study.
  9. Is a female of childbearing potential pregnant or breastfeeding.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A - CLE-100 (oral esketamine)
Part A: 1 oral tablet of CLE-100 once daily for 1 week.
1 tablet of CLE-100 administered once daily
Placebo Comparator: Part A - Placebo
Part A: 1 oral tablet of Placebo once daily for 1 week.
1 tablet of placebo administered once daily
Experimental: Part B - CLE-100 (oral esketamine)
Part B: 1 oral tablet of CLE-100 once daily for 4 weeks.
1 tablet of CLE-100 administered once daily
Placebo Comparator: Part B - Placebo
Part B: 1 oral tablet of Placebo once daily for 4 weeks.
1 tablet of placebo administered once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A - Frequency of adverse events
Time Frame: 14 days
14 days
Part A - Self-Administered Karolinska Sleepiness Scale
Time Frame: 7 days
The Karolinska Sleepiness Scale is a single-item, subjective, self-reported instrument measuring sleepiness on a 9-point Likert scale (1 to 9), where a higher value represents a worse outcome.
7 days
Part A - Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S)
Time Frame: 7 days
The MOAA/S will be used to measure treatment-emergent sedation. The MOAA/S is a widely used clinician-administered measure of alertness/sedation for clinical trials. The MOAA/S measures the alertness/sedation spectrum on a 6-point scale (0 to 5) based on verbal cues, where a higher value represents a better outcome.
7 days
Part A - Clinician-Administered Dissociative Symptoms Scale (CADSS)
Time Frame: 7 days
The CADSS will be administered to assess treatment-emergent dissociative symptoms. The CADSS is a 23-item instrument that is clinician-administered. Each item is scored on a 5-point scale (0 to 4. A higher value represents a worse outcome. The CADSS total score ranges between 0 and 92.
7 days
Part A - Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: 7 days
The C-SSRS will be performed to assess suicidal ideation and behavior. The C-SSRS is an instrument used to assess suicide risk by measuring symptoms of suicidal ideation, self-harm, and suicidal behavior that is administered by trained personnel. The suicidal ideation is evaluated with a "yes/no" questionnaire and the suicidal behavior severity is scored on a 6-point scale (0 to 5) where a higher value represents a more severe behavior.
7 days
Part A - Four-items positive subscale from the Brief Psychiatric Rating Scale (BPRS)
Time Frame: 7 days
Four items of the BPRS will be administered to assess treatment-emergent psychotic symptoms. The BPRS is a widely used, clinician-administered instrument that involves 4 subscales: Negative Symptoms, Positive Symptoms, Manic-Hostility, and Anxiety/Depression. The 4-item Positive Symptoms subscale of the BPRS will be used to screen for potential psychiatric symptoms (suspiciousness, hallucinations, unusual thought content, and conceptual disorganization). Each item is scored on a 7-point scale (1 to 7). where a higher value represents a worse outcome. The 4 items BPRS total score ranges between 4 and 28.
7 days
Part A - 20-item Physician Withdrawal Checklist (PWC-20)
Time Frame: 14 days
The PWC-20 is a clinician-administered assessment to evaluate potential withdrawal symptoms following cessation of the double-blind treatment. The PWC-20 is a shortened version of the original 35-item instrument used to determine withdraw symptoms in subjects following discontinuation of anxiolytics. The items are evaluated on a 4-point scale (0 to 3) where a higher value represents a worse outcome. The total score ranges between 0 to 60.
14 days
Part A - Cognitive function evaluated by Cogstate battery
Time Frame: 7 days
The Cogstate battery of cognitive tests will be used to measure psychomotor function, attention, visual learning, and working memory. The Cogstate battery will include the following tests: Detection Test, Identification Test, One Back Test, Groton Maze Test.
7 days
Part A - Digit Symbol Substitution Test (DSST)
Time Frame: 7 days
The DSST is a psychometric test assessing the integrity of executive function, processing speed, attention, spatial perception, and visual scanning, which are functions required for driving, and will be performed repeatedly. The DSST is a valid and sensitive instrument to evaluate cognitive dysfunction and changes in cognitive function. The DSST is a timed test taken by the subject and scored based on both the number of correct answers and the speed at which they were determined. The score ranges between 0 to 135.
7 days
Part A - Pharmacokinetics of CLE-100 (Cmax)
Time Frame: 7 days
Maximum observed plasma concentration (Cmax)
7 days
Part A - Pharmacokinetics of CLE-100 (Tmax)
Time Frame: 7 days
Time of maximum observed plasma concentration (Tmax)
7 days
Part A - Pharmacokinetics of CLE-100 (AUC)
Time Frame: 8 days
Area under the concentration curve
8 days
Part B - Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score
Time Frame: 29 days
The MADRS is a validated clinician-administered measurement of depression severity commonly used in clinical trials of depression treatments to select subjects and assess efficacy. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
29 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part B - Change from baseline in Symptoms of Depression Questionnaire (SDQ) score
Time Frame: 29 days
The SDQ is a 44-item self-report scale for the assessment of MDD that includes assessments for irritability, anger attacks, and anxiety symptoms. Higher scores represent a more severe condition.
29 days
Part B - Change from baseline in Sheehan Disability Scale (SDS)
Time Frame: 29 days
The SDS is a 3-item, self-completion instrument to assess functional impairments associated with work/school, social life and leisure activities, and family life and home responsibilities utilizing a 10-point scale.
29 days
Part B - Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score
Time Frame: 15 days
The MADRS is a validated clinician-administered measurement of depression severity commonly used in clinical trials of depression treatments to select subjects and assess efficacy. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
15 days
Part B - Change from baseline in Clinical Global Impression - Severity (CGI-S) score
Time Frame: 29 days
The CGI-S is a well-known and frequently used clinician-administered instrument for the assessment of MDD that weighs the clinical impact of the identified symptom(s) on behavior and function. The CGI-S grades measures of psychopathology on a scale from 1 to 7.
29 days

Collaborators and Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

September 5, 2019

Primary Completion (Actual)

September 21, 2022

Study Completion (Actual)

October 5, 2022

Study Registration Dates

First Submitted

September 9, 2019

First Submitted That Met QC Criteria

September 24, 2019

First Posted (Actual)

September 26, 2019

Study Record Updates

Last Update Posted (Actual)

November 15, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

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

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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