Adjunctive Treatment of Major Depressive DisorderPhase 2NCT04103892
A Study of CLE-100 (Oral Esketamine) in Addition to Standard Antidepressant Drug for Major Depressive Disorder - CLEO Study
A Phase 2 study testing CLE-100 in people with Adjunctive Treatment of Major Depressive Disorder, run by Clexio Biosciences Ltd. at 46 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Adjunctive Treatment of Major Depressive Disorder
- What is being tested?
- CLE-100
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 46 sitesin 2 countries
- Study dates
- 5 Sep 2019to 5 Oct 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Part A - Inclusion Criteria:
- Male or female between 18 to 60 years of age
- Primary diagnosis of MDD, without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
- MADRS score of at least 18 at Screening
- Treatment with stable dose of the current antidepressant therapy for at least 4 weeks for the current major depressive episode (MDE)
- Body mass index (BMI) between 18 and 40 kg/m2, inclusive
- Is able and competent to read and sign the informed consent form (ICF).
Part A - Exclusion Criteria:
- History of substance use disorder per DSM-5 criteria, except for tobacco use disorder
- History or current diagnosis of bipolar disorder, schizophrenia, schizoaffective disorders, binge eating disorder dementia, delirium, amnesia, or any other significant cognitive disorder
- Posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders)
- Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk
- Female of childbearing potential without appropriate contraceptive means, pregnant or breastfeeding
Part B - Inclusion Criteria:
- Male or female between 18 to 65 years of age
- Primary diagnosis of MDD without psychotic features according to DSM-5 and supported by the Mini International Neuropsychiatric Interview (MINI)
- MADRS score of at least 24 at Screening.
- At least 2 inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE)
- Current MDE for at least 12 weeks
- BMI between 18 and 40 kg/m2, inclusive.
- Is able and competent to read and sign the ICF.
Part B - Exclusion Criteria:
- Inadequate response to more than 5 treatment courses of antidepressant medication therapy during the current MDE
- Current MDE for longer than 5 years.
- 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.
- Has a history or current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorders.
- Has dementia, delirium, amnesia, or any other significant cognitive disorder.
- Has posttraumatic stress disorder, obsessive compulsive disorder, or any other mental disorder (including personality disorders, eating disorders, etc.).
- Has any medical condition for which an increase in blood pressure or intracranial pressure poses a serious risk.
- Has been randomized in Part A of this study.
- Is a female of childbearing potential pregnant or breastfeeding.
Trial locations and contacts
46 sites in 2 countries.
46 sites in 2 countries
United States45 sites
Clinical Site 141
Anaheim, California, 92805
Clinical Site 140
Atlanta, Georgia, 30338
Clinical Site 131
Baltimore, Maryland, 21208
Clinical Site 135
Bellevue, Washington, 98007
Clinical Site 115
Bellflower, California, 90706
Clinical Site 126
Bentonville, Arkansas, 72712
Clinical Site 103
Boston, Massachusetts, 02114
Clinical Site 121
Boston, Massachusetts, 02131
Clinical Site 151
Dearborn Heights, Michigan, 48034
Clinical Site 104
Decatur, Georgia, 30030
Clinical Site 145
Denver, Colorado, 80209
Clinical Site 147
Draper, Utah, 84020
Clinical Site 114
Fort Worth, Texas, 76104
Clinical Site 107
Hialeah, Florida, 33016
Clinical Site 111
Hickory, North Carolina, 28601
Clinical Site 109
Houston, Texas, 77030
Clinical Site 132
Lafayette, California, 94549
Clinical Site 110
Las Vegas, Nevada, 89102
Clinical Site 125
Lincoln, Nebraska, 68526
Clinical Site 120
Little Rock, Arkansas, 72209
Clinical Site 129
Little Rock, Arkansas, 72209
Clinical Site 122
Marietta, Georgia, 30060
Clinical Site 101
Marlton, New Jersey, 08053
Clinical Site 106
Media, Pennsylvania, 19063
Clinical Site 116
Miami, Florida, 33145
Clinical Site 108
Miami Gardens, Florida, 33014
Clinical Site 138
Middleburg Heights, Ohio, 44130
Clinical Site 149
Missouri City, Texas, 88459
Clinical Site 128
New York, New York, 10036
Clinical Site 127
North Canton, Ohio, 44720
Clinical Site 117
Oakland, California, 94607
Clinical Site 113
Oceanside, California, 92056
Clinical Site 105
Orlando, Florida, 32803
Clinical Site 137
Orlando, Florida, 32807
Clinical Site 118
Philadelphia, Pennsylvania, 19104
Clinical Site 144
Plano, Texas, 75093
Clinical Site 143
Raleigh, North Carolina, 27609
Clinical Site 123
Riverside, California, 92506
Clinical Site 136
Rockville, Maryland, 20877
Clinical Site 124
Santa Ana, California, 92705
Clinical Site 142
Santa Rosa, California, 95401
Clinical Site 139
St Louis, Missouri, 63128
Clinical Site 102
Staten Island, New York, 10312
Clinical Site 148
Toms River, New Jersey, 08755
Clinical Site 112
Torrance, California, 90502
About this study
Official title: 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.
Read the 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.
- Being tested
- CLE-100, placebo
- Keywords
- MDD, depression, depressive disorder, major depression, adjunct therapy, oral, esketamine
- Medical subject headings
- Depression, Depressive Disorder, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLE-100Drug
1 tablet of CLE-100 administered once daily
placeboDrug
1 tablet of placebo administered once daily
| Study group | Role | What they receive |
|---|---|---|
| Part A - CLE-100 (oral esketamine) | Experimental | Part A: 1 oral tablet of CLE-100 once daily for 1 week. Receives: Drug: CLE-100 |
| Part A - Placebo | Placebo comparator | Part A: 1 oral tablet of Placebo once daily for 1 week. Receives: Drug: placebo |
| Part B - CLE-100 (oral esketamine) | Experimental | Part B: 1 oral tablet of CLE-100 once daily for 4 weeks. Receives: Drug: CLE-100 |
| Part B - Placebo | Placebo comparator | Part B: 1 oral tablet of Placebo once daily for 4 weeks. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 29 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2019
- Study start5 Sep 2019
- Primary completion21 Sep 2022
- Study completion5 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adjunctive Treatment of Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Part A - 16 patients, 2 arms, parallel; Part B - 130 patients, 2 arms, parallel
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clexio Biosciences Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04103892
- Sponsor's protocol ID
- CLE100-MDD-201
- Status last verified
- Sep 2025
- First submitted
- 9 Sep 2019
- Last updated
- 14 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part Study of CLE-100 as an Adjunct Therapy in Subjects With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT04103892
- Acronym / sponsor ID
- CLE100-MDD-201
- Keywords
- MDD, depression, depressive disorder, major depression, adjunct therapy, oral, esketamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- Clexio Biosciences Ltd.Industry (pharma, biotech, devices)
- Study start
- 5 Sep 2019 (actual)
- Primary completion
- 21 Sep 2022 (actual)
- Study completion
- 5 Oct 2022 (actual)
- First posted
- 26 Sep 2019 (actual)
- Results
- Posted 24 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- Part A - 16 patients, 2 arms, parallel; Part B - 130 patients, 2 arms, parallel
| Arm | Type | Receives |
|---|---|---|
| Part A - CLE-100 (oral esketamine) | Experimental | Drug: CLE-100Part A: 1 oral tablet of CLE-100 once daily for 1 week. |
| Part A - Placebo | Placebo comparator | Drug: placeboPart A: 1 oral tablet of Placebo once daily for 1 week. |
| Part B - CLE-100 (oral esketamine) | Experimental | Drug: CLE-100Part B: 1 oral tablet of CLE-100 once daily for 4 weeks. |
| Part B - Placebo | Placebo comparator | Drug: placeboPart B: 1 oral tablet of Placebo once daily for 4 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CLE-1001 tablet of CLE-100 administered once daily | Drug | Part A - CLE-100 (oral esketamine), Part B - CLE-100 (oral esketamine) |
| placebo1 tablet of placebo administered once daily | Drug | Part A - Placebo, Part B - Placebo |
Primary outcome
Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
46 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CLE-100 in people with Adjunctive Treatment of Major Depressive Disorder, run by Clexio Biosciences Ltd. at 46 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part B - Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score (time frame: 29 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2025.