Clinical trial NCT04103892: A Study of CLE-100 (Oral Esketamine) in Addition to Standard Antidepressant Drug for Major Depressive Disorder - CLEO Study
Official title: A Two-Part Study of CLE-100 as an Adjunct Therapy in Subjects With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adjunctive Treatment of Major Depressive Disorder
Keywords: MDD
depression
depressive disorder
major depression
adjunct therapy
oral
esketamine
Lead sponsor: Clexio Biosciences Ltd.
Sponsor class: INDUSTRY
First posted: 2019-09-26
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A - 15 patients, 2 arms, parallel; Part B - 122 patients, 2 arms, parallel
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A - Frequency of adverse events
timeFrame: 14 days
measure: Part A - Self-Administered Karolinska Sleepiness Scale
timeFrame: 7 days
measure: Part A - Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S)
timeFrame: 7 days
measure: Part A - Clinician-Administered Dissociative Symptoms Scale (CADSS)
timeFrame: 7 days
measure: Part A - Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: 7 days
measure: Part A - Four-items positive subscale from the Brief Psychiatric Rating Scale (BPRS)
timeFrame: 7 days
measure: Part A - 20-item Physician Withdrawal Checklist (PWC-20)
timeFrame: 14 days
measure: Part A - Cognitive function evaluated by Cogstate battery
timeFrame: 7 days
measure: Part A - Digit Symbol Substitution Test (DSST)
timeFrame: 7 days
measure: Part A - Pharmacokinetics of CLE-100 (Cmax)
timeFrame: 7 days
measure: Part A - Pharmacokinetics of CLE-100 (Tmax)
timeFrame: 7 days
measure: Part A - Pharmacokinetics of CLE-100 (AUC)
timeFrame: 8 days
measure: Part B - Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score
timeFrame: 29 days
Secondary outcomes:
measure: Part B - Change from baseline in Symptoms of Depression Questionnaire (SDQ) score
timeFrame: 29 days
measure: Part B - Change from baseline in Sheehan Disability Scale (SDS)
timeFrame: 29 days
measure: Part B - Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score
timeFrame: 15 days
measure: Part B - Change from baseline in Clinical Global Impression - Severity (CGI-S) score
timeFrame: 29 days
Other outcomes:
Locations:
city: Bentonville
country: United States
facility: Clinical Site 126
state: Arkansas
city: Little Rock
country: United States
facility: Clinical Site 120
state: Arkansas
city: Little Rock
country: United States
facility: Clinical Site 129
state: Arkansas
city: Anaheim
country: United States
facility: Clinical Site 141
state: California
city: Bellflower
country: United States
facility: Clinical Site 115
state: California
city: Lafayette
country: United States
facility: Clinical Site 132
state: California
city: Oakland
country: United States
facility: Clinical Site 117
state: California
city: Oceanside
country: United States
facility: Clinical Site 113
state: California
city: Riverside
country: United States
facility: Clinical Site 123
state: California
city: Santa Ana
country: United States
facility: Clinical Site 124
state: California
city: Santa Rosa
country: United States
facility: Clinical Site 142
state: California
city: Torrance
country: United States
facility: Clinical Site 112
state: California
city: Denver
country: United States
facility: Clinical Site 145
state: Colorado
city: Hialeah
country: United States
facility: Clinical Site 107
state: Florida
city: Miami Gardens
country: United States
facility: Clinical Site 108
state: Florida
city: Miami
country: United States
facility: Clinical Site 116
state: Florida
city: Orlando
country: United States
facility: Clinical Site 105
state: Florida
city: Orlando
country: United States
facility: Clinical Site 137
state: Florida
city: Atlanta
country: United States
facility: Clinical Site 140
state: Georgia
city: Decatur
country: United States
facility: Clinical Site 104
state: Georgia
city: Marietta
country: United States
facility: Clinical Site 122
state: Georgia
city: Baltimore
country: United States
facility: Clinical Site 131
state: Maryland
city: Rockville
country: United States
facility: Clinical Site 136
state: Maryland
city: Boston
country: United States
facility: Clinical Site 103
state: Massachusetts
city: Boston
country: United States
facility: Clinical Site 121
state: Massachusetts
city: Dearborn Heights
country: United States
facility: Clinical Site 151
state: Michigan
city: Saint Louis
country: United States
facility: Clinical Site 139
state: Missouri
city: Lincoln
country: United States
facility: Clinical Site 125
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Site 110
state: Nevada
city: Marlton
country: United States
facility: Clinical Site 101
state: New Jersey
city: Toms River
country: United States
facility: Clinical Site 148
state: New Jersey
city: New York
country: United States
facility: Clinical Site 128
state: New York
city: Staten Island
country: United States
facility: Clinical Site 102
state: New York
city: Hickory
country: United States
facility: Clinical Site 111
state: North Carolina
city: Raleigh
country: United States
facility: Clinical Site 143
state: North Carolina
city: Middleburg Heights
country: United States
facility: Clinical Site 138
state: Ohio
city: North Canton
country: United States
facility: Clinical Site 127
state: Ohio
city: Media
country: United States
facility: Clinical Site 106
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Site 118
state: Pennsylvania
city: Fort Worth
country: United States
facility: Clinical Site 114
state: Texas
city: Houston
country: United States
facility: Clinical Site 109
state: Texas
city: Missouri City
country: United States
facility: Clinical Site 149
state: Texas
city: Plano
country: United States
facility: Clinical Site 144
state: Texas
city: Draper
country: United States
facility: Clinical Site 147
state: Utah
city: Bellevue
country: United States
facility: Clinical Site 135
state: Washington
city: San Juan
country: Puerto Rico
facility: Clinical Site 150
Study officials:
References: