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A Study of CLE-100 (oral Esketamine) As an Adjunctive Treatment to Standard Antidepressants for Major Depressive Disorder

Phase 2
Recruiting
Conditions
Adjunctive Treatment of Major Depressive Disorder (MDD)
Interventions
Drug: Placebo
Registration Number
NCT06340958
Lead Sponsor
Clexio Biosciences Ltd.
Brief Summary

The study is a Phase 2, double-blind, randomized, placebo-controlled study in Major Depressive Disorder (MDD) participants with an inadequate response to standard antidepressants The objective of the study is to assess CLE-100 (oral esketamine) for the treatment of MDD in participants currently treated with an oral antidepressant medication and who have an inadequate response to at least 2 antidepressants.

Detailed Description

This is a Phase 2 study in subjects with MDD currently treated with an oral antidepressant medication with an inadequate response to at least 2 antidepressants. SOLEO will be an outpatient study to assess the safety, efficacy, and tolerability of CLE-100 as compared to placebo.

Eligible subjects will be randomized to receive either placebo or CLE-100 (oral esketamine) once daily in addition to their current oral antidepressant monotherapy for 4 weeks. All subjects who adequately completed the 4-week Double-Blind Treatment Period and who meet the eligibility criteria will be offered the option to roll-over to a 6-month Open-label Extension (OLE) Treatment Period with CLE-100.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
Inclusion Criteria
  1. Male or female between 18 to 65 years of age at Screening
  2. Diagnosis of MDD, single or recurrent, without psychotic features, in the current or previous episode(s), according to the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). The diagnosis of MDD must be supported by the Mini International Neuropsychiatric Interview (MINI) Screen 7.0.2 for DSM-5.
  3. Currently experiencing a Major Depressive Episode (MDE) that began at least 12 weeks but no more than 5 years prior to Screening. The current MDE must be confirmed by the independent SAFER assessor.
  4. MADRS score of 24 or higher at Screening as confirmed by an independent SAFER assessor.
  5. At Screening, a history of inadequate response to at least 2 antidepressant medications in the current MDE. Inadequate response is defined as less than 50% improvement of depression symptoms following at least 6 weeks of treatment with a therapeutic dose and is assessed by the site using the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ). Inadequate response to at least 2 antidepressant medications must be verified by documented medical or pharmacy records and confirmed by an independent SAFER assessor.
  6. Able and competent to read and sign the informed consent form (ICF).
Exclusion Criteria
  1. At Screening, a history of inadequate response (as defined in inclusion criterion #5) to more than 5 antidepressant medications in the current MDE using MGH-ATRQ and confirmed by the independent SAFER assessor.

  2. A high risk of suicide based on any of the following:

    1. Item 10 of MADRS score (suicidal thoughts) is 5 or higher at Screening or Baseline.
    2. Suicide attempt in the previous 6 months.
    3. Significant risk, as judged by the Investigator, based on the psychiatric interview or information collected with the C SSRS at Screening or Baseline.
  3. Current or lifetime history of substance use disorder with ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3.4-methylenedioxymethamphetamine (MDMA) hallucinogen-related use disorders or has any other current substance use disorder or history within 12 months prior to Screening (Substance Use Disorder is diagnosed per DSM-5 criteria and does not include tobacco use disorder).

  4. Use of ketamine, esketamine, PCP, or dextromethorphan recreationally in the past 6 months.

  5. History or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder or other schizophrenia spectrum disorders.

  6. Dementia, delirium, amnesia, or any other significant cognitive disorder.

  7. Any medical condition for which an increase in blood pressure or intracranial pressure or intraocular pressure or tachycardia poses a serious risk (e.g., aneurysmal vascular disease, arteriovenous malformation, or history of intracerebral hemorrhage).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CLE-100CLE-1001 oral tablet of CLE-100 once daily (in addition to current anti-depressant drug) for 4 weeks
PlaceboPlacebo1 oral tablet of Placebo once daily (in addition to current anti-depressant drug) for 4 weeks.
Primary Outcome Measures
NameTimeMethod
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score29 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.

Secondary Outcome Measures
NameTimeMethod
Safety Outcomes: Assessment of the safety and tolerability of CLE-100 compared to placeboThrough study completion, an average of 7 months

Assessment of the safety and tolerability of CLE-100 compared to placebo using the following assessments:

* Adverse Events (AEs)

* Adverse events of special interest (AESIs)

* Clinical laboratory evaluations

* Vital signs

* 12-lead electrocardiogram

* Modified Observer's Assessment of Alertness/Sedation scale (MOAA/S)

* Clinician-Administered Dissociative State Scale (CADSS)

* Incidence of suicidal ideation or behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

* 4-item Brief Psychiatric Rating Scale (BPRS)

* 20-item Physician Withdrawal Checklist (PWC-20)

* Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS)

* Digit Symbol Substitution Test (DSST)

* Discontinuation rates and reason(s) for discontinuation

Change from Baseline in the Clinical Global Impression - Severity (CGI-S)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.

Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score2 weeks

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.

Trial Locations

Locations (23)

Clinical Site 139

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La Jolla, California, United States

Clinical Site 131

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Lafayette, California, United States

Clinical Site 130

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Upland, California, United States

Clinical Site 102

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Hollywood, Florida, United States

Clinical Site 105

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Lauderhill, Florida, United States

Clinical Site 140

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Miami Springs, Florida, United States

Clinical Site 132

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Pensacola, Florida, United States

Clinical Site 118

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Atlanta, Georgia, United States

Clinical Site 138

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Marietta, Georgia, United States

Clinical Site 114

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Savannah, Georgia, United States

Clinical Site 127

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Chicago, Illinois, United States

Clinical Site 120

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Elgin, Illinois, United States

Clinical Site 108

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Gaithersburg, Maryland, United States

Clinical Site 116

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Flowood, Mississippi, United States

Clinical Site 126

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O'Fallon, Missouri, United States

Clinical Site 101

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Toms River, New Jersey, United States

Clinical Site 103

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Beachwood, Ohio, United States

Clinical Site 119

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North Canton, Ohio, United States

Clinical Site 135

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Oklahoma City, Oklahoma, United States

Clinical Site 107

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Austin, Texas, United States

Clinical Site 137

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Plano, Texas, United States

Clinical Site 117

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Murray, Utah, United States

Clinical Site 115

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Bellevue, Washington, United States

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