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

Adjunctive Treatment of Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04103892
• Other study ID #: CLE100-MDD-201
• Status: Completed
• Phase: Phase 2
• Start date: September 5, 2019
• Est. completion date: October 5, 2022

Study information

• Verified date: November 2023
• Source: Clexio Biosciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: October 5, 2022
• Est. primary completion date: September 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adjunctive Treatment of Major Depressive Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

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

Locations

Country	Name	City	State
Puerto Rico	Clinical Site 150	San Juan
United States	Clinical Site 141	Anaheim	California
United States	Clinical Site 140	Atlanta	Georgia
United States	Clinical Site 131	Baltimore	Maryland
United States	Clinical Site 135	Bellevue	Washington
United States	Clinical Site 115	Bellflower	California
United States	Clinical Site 126	Bentonville	Arkansas
United States	Clinical Site 103	Boston	Massachusetts
United States	Clinical Site 121	Boston	Massachusetts
United States	Clinical Site 151	Dearborn Heights	Michigan
United States	Clinical Site 104	Decatur	Georgia
United States	Clinical Site 145	Denver	Colorado
United States	Clinical Site 147	Draper	Utah
United States	Clinical Site 114	Fort Worth	Texas
United States	Clinical Site 107	Hialeah	Florida
United States	Clinical Site 111	Hickory	North Carolina
United States	Clinical Site 109	Houston	Texas
United States	Clinical Site 132	Lafayette	California
United States	Clinical Site 110	Las Vegas	Nevada
United States	Clinical Site 125	Lincoln	Nebraska
United States	Clinical Site 120	Little Rock	Arkansas
United States	Clinical Site 129	Little Rock	Arkansas
United States	Clinical Site 122	Marietta	Georgia
United States	Clinical Site 101	Marlton	New Jersey
United States	Clinical Site 106	Media	Pennsylvania
United States	Clinical Site 116	Miami	Florida
United States	Clinical Site 108	Miami Gardens	Florida
United States	Clinical Site 138	Middleburg Heights	Ohio
United States	Clinical Site 149	Missouri City	Texas
United States	Clinical Site 128	New York	New York
United States	Clinical Site 127	North Canton	Ohio
United States	Clinical Site 117	Oakland	California
United States	Clinical Site 113	Oceanside	California
United States	Clinical Site 105	Orlando	Florida
United States	Clinical Site 137	Orlando	Florida
United States	Clinical Site 118	Philadelphia	Pennsylvania
United States	Clinical Site 144	Plano	Texas
United States	Clinical Site 143	Raleigh	North Carolina
United States	Clinical Site 123	Riverside	California
United States	Clinical Site 136	Rockville	Maryland
United States	Clinical Site 139	Saint Louis	Missouri
United States	Clinical Site 124	Santa Ana	California
United States	Clinical Site 142	Santa Rosa	California
United States	Clinical Site 102	Staten Island	New York
United States	Clinical Site 148	Toms River	New Jersey
United States	Clinical Site 112	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Clexio Biosciences Ltd.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A - Frequency of adverse events		14 days
Primary	Part A - Self-Administered Karolinska Sleepiness Scale	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
Primary	Part A - Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S)	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
Primary	Part A - Clinician-Administered Dissociative Symptoms Scale (CADSS)	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
Primary	Part A - Columbia Suicide Severity Rating Scale (C-SSRS)	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
Primary	Part A - Four-items positive subscale from the Brief Psychiatric Rating Scale (BPRS)	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
Primary	Part A - 20-item Physician Withdrawal Checklist (PWC-20)	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
Primary	Part A - Cognitive function evaluated by Cogstate battery	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
Primary	Part A - Digit Symbol Substitution Test (DSST)	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
Primary	Part A - Pharmacokinetics of CLE-100 (Cmax)	Maximum observed plasma concentration (Cmax)	7 days
Primary	Part A - Pharmacokinetics of CLE-100 (Tmax)	Time of maximum observed plasma concentration (Tmax)	7 days
Primary	Part A - Pharmacokinetics of CLE-100 (AUC)	Area under the concentration curve	8 days
Primary	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	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
Secondary	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
Secondary	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
Secondary	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