Adjunctive Treatment of Major Depressive Disorder
Conditions
Keywords
MDD, depression, depressive disorder, major depression, adjunct therapy, oral, esketamine
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). 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.
Interventions
DRUGCLE-100
1 tablet of CLE-100 administered once daily
DRUGplacebo
1 tablet of placebo administered once daily
Sponsors
Clexio Biosciences Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Part A - 16 patients, 2 arms, parallel; Part B - 130 patients, 2 arms, parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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 -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score | 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. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A - CLE-100 (Oral Esketamine) Part A: 1 oral tablet of CLE-100 once daily for 1 week.
CLE-100: 1 tablet of CLE-100 administered once daily | 13 |
| Part A - Placebo Part A: 1 oral tablet of Placebo once daily for 1 week.
placebo: 1 tablet of placebo administered once daily | 3 |
| Part B - CLE-100 (Oral Esketamine) Part B: 1 oral tablet of CLE-100 once daily for 4 weeks.
CLE-100: 1 tablet of CLE-100 administered once daily | 72 |
| Part B - Placebo Part B: 1 oral tablet of Placebo once daily for 4 weeks.
placebo: 1 tablet of placebo administered once daily | 58 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 1 |
| Overall Study | Requirement of prohibited concomitant medication | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 | 5 |
Baseline characteristics
| Characteristic | Part A - CLE-100 (Oral Esketamine) | Total | Part B - Placebo | Part B - CLE-100 (Oral Esketamine) | Part A - Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 50.23 years STANDARD_DEVIATION 9.99 | 44.93 years STANDARD_DEVIATION 12.98 | 46.19 years STANDARD_DEVIATION 13.14 | 42.79 years STANDARD_DEVIATION 13.24 | 49.00 years STANDARD_DEVIATION 7.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 40 Participants | 24 Participants | 15 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 104 Participants | 33 Participants | 57 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 0 Participants | 6 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 34 Participants | 10 Participants | 11 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 103 Participants | 46 Participants | 54 Participants | 0 Participants |
| Region of Enrollment Puerto Rico | 0 participants | 2 participants | 0 participants | 2 participants | 0 participants |
| Region of Enrollment United States | 13 participants | 144 participants | 58 participants | 70 participants | 3 participants |
| Sex: Female, Male Female | 5 Participants | 101 Participants | 43 Participants | 51 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 45 Participants | 15 Participants | 21 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 3 | 0 / 72 | 0 / 57 |
| other Total, other adverse events | 6 / 13 | 1 / 3 | 37 / 72 | 23 / 57 |
| serious Total, serious adverse events | 0 / 13 | 0 / 3 | 0 / 72 | 0 / 57 |
Outcome results
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.
Time frame: 29 days
Population: The Full Analysis Set (FAS), which is a subset of the ITT Analysis Set, includes all data collected while on study drug for all randomized subjects who received at least 1 dose of study drug during Part B and have both Baseline and at least 1 post-baseline MADRS total score. This Analysis Set serves as the principal analysis set for inference.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part B - CLE-100 (Oral Esketamine) | Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score | -10.72 units on a scale | Standard Error 1.13 |
| Part B - Placebo | Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score | -9.46 units on a scale | Standard Error 1.31 |
p-value: 0.4695% CI: [-4.6, 2.09]Mixed Models Repeated Measures (MMRM
Post Hoc
Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score in 2022 Cohort (Corresponding to a Post-acute Phase of the COVID-19 Pandemic)
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.
Time frame: 29 days
Population: 2022 cohort (corresponding to a post-acute phase of the COVID-19 pandemic) of the Full Analysis Set (FAS) includes all data collected while on study drug for all randomized subjects in 2022 who received at least 1 dose of study drug during Part B and have both Baseline and at least 1 post-baseline MADRS total score. This Analysis Set serves as the principal analysis set for inference.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part B - CLE-100 (Oral Esketamine) | Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score in 2022 Cohort (Corresponding to a Post-acute Phase of the COVID-19 Pandemic) | -12.96 units on a scale | Standard Error 1.6 |
| Part B - Placebo | Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score in 2022 Cohort (Corresponding to a Post-acute Phase of the COVID-19 Pandemic) | -7.68 units on a scale | Standard Error 1.84 |
p-value: 0.0395% CI: [-9.91, -0.65]Mixed Models Repeated Measures (MMRM)