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

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
• Conditions: Adjunctive Treatment of Major Depressive Disorder
• Intervention / Treatment: Drug: CLE-100; Drug: placebo

Detailed Description

CLEO study is performed in two parts (part A and Part B). 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): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Clinical Site 150
• United States
  • 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
    • St 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

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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

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.	Drug: CLE-100; 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.	Drug: placebo; 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.	Drug: CLE-100; 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.	Drug: placebo; 1 tablet of placebo administered once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score	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	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)	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	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	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

• Sponsor: Clexio Biosciences Ltd.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

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 (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: September 28, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: depression; MDD; esketamine; oral; depressive disorder; major depression; adjunct therapy
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Behavior; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: CLE100-MDD-201

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