Esketamine for Major Depressive Disorder

(SOLEO Trial)

Overseen By Patient Information Page https://www.osmind.org/SOLEO-Study-Patient-Information-Page

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Clexio Biosciences Ltd.

Must be taking: Antidepressants

Must not be taking: Ketamine, PCP, LSD, MDMA

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication called CLE-100 (also known as Oral Esketamine) for individuals with Major Depressive Disorder (MDD) who haven't found success with at least two antidepressant medications. Participants will take either CLE-100 or a placebo (a pill with no active medicine) alongside their current antidepressant for four weeks. The trial targets those experiencing a major depressive episode that began at least 12 weeks ago but not more than five years ago. Individuals who have tried and not responded well to more than five antidepressants or have a history of substance misuse are not eligible. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of new therapies for MDD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have an inadequate response to at least 2 antidepressants, suggesting you may continue your current antidepressant.

Is there any evidence suggesting that CLE-100 is likely to be safe for humans?

Research has shown that oral esketamine, like CLE-100, is under evaluation for safety in treating Major Depressive Disorder (MDD) when other antidepressants prove ineffective. Previous patients have demonstrated that most people can tolerate esketamine, though it may cause side effects such as dizziness or nausea. Studies suggest these side effects are usually mild to moderate.

The FDA has approved esketamine for other depression treatments, indicating prior safety evaluations. However, new studies like this one are crucial to confirm its efficacy and safety for this specific use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MDD?

Researchers are excited about CLE-100 for major depressive disorder because it introduces a novel approach by incorporating esketamine, a derivative of ketamine, which works rapidly. Unlike traditional antidepressants that often take weeks to show effectiveness, CLE-100 has the potential to alleviate symptoms in just days. This rapid action is due to its unique mechanism that targets the brain's NMDA receptors, differing from the usual serotonin or norepinephrine pathways. Additionally, its oral tablet form offers a convenient alternative to the nasal spray delivery method of some esketamine treatments, making it easier for patients to use alongside their current antidepressant regimen.

What evidence suggests that CLE-100 might be an effective treatment for Major Depressive Disorder?

Research has shown that CLE-100 (oral esketamine), which participants in this trial may receive, may help treat Major Depressive Disorder (MDD), especially for those who haven't found relief with other antidepressants. In one study, patients taking oral esketamine showed significant improvements in their depression symptoms. Another study found that esketamine not only eased depressive symptoms but also enhanced overall quality of life. Researchers measured these improvements using the Montgomery-Åsberg Depression Rating Scale, which assesses the severity of depression. These findings suggest that CLE-100 could be a helpful option for people dealing with MDD. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Major Depressive Disorder (MDD) who haven't had enough improvement from at least two standard antidepressants. Participants must be currently taking an oral antidepressant.

Inclusion Criteria

Have you been experiencing a Major Depressive Episode for at least 12 weeks?

Have you tried at least 2 antidepressant medications without relief?

MADRS score of 24 or higher at Screening as confirmed by an independent SAFER assessor

Exclusion Criteria

Have you been diagnosed with Bipolar Disorder or Schizophrenia or Schizoaffective Disorder?

Do you struggle with dementia, amnesia, delirium, or any other significant cognitive disorder?

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or CLE-100 (oral esketamine) once daily in addition to their current oral antidepressant monotherapy

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension

Participants who complete the Double-Blind Treatment Period and meet eligibility criteria may continue with CLE-100 for an additional 6 months

6 months

What Are the Treatments Tested in This Trial?

Interventions

• CLE-100

Trial Overview

The study tests CLE-100, a form of oral esketamine, as an add-on to existing antidepressant treatment versus a placebo. It's a Phase 2 trial where participants are randomly assigned to either the test drug or placebo without knowing which one they receive.

How Is the Trial Designed?

Group I: CLE-100 Experimental Treatment 1 Intervention

1 oral tablet of CLE-100 once daily (in addition to current anti-depressant drug) for 4 weeks

Group II: Placebo Placebo Group 1 Intervention

1 oral tablet of Placebo once daily (in addition to current anti-depressant drug) for 4 weeks.

Who Is Running the Clinical Trial?

Clexio Biosciences Ltd.

Lead Sponsor

Trials

3

Recruited

280+

Published Research Related to This Trial

A study analyzing 720 cases of esketamine-related neurological adverse events (AEs) from 2019 to 2021 identified 21 safety signals, with sedation being the most concerning (ROR of 204.00), indicating potential long-term safety issues with esketamine.

The severity of neurological AEs was influenced by factors such as esketamine dosage and co-prescription with other medications, highlighting the need for careful monitoring and management of these risks in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological Adverse Events Associated With Esketamine: A Disproportionality Analysis for Signal Detection Leveraging the FDA Adverse Event Reporting System. Guo, H., Wang, B., Yuan, S., et al.[2022]

Esketamine offers a new treatment option for patients with major depressive disorder (MDD) who have not responded adequately to two or more antidepressant therapies, addressing a significant gap in care for those with moderate to severe depression.

An expert panel of 11 professionals has developed practical recommendations for establishing esketamine clinics in Australia, focusing on patient selection, administration, adverse event management, and long-term follow-up to ensure effective treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishing an esketamine clinic in Australia: Practical recommendations and clinical guidance from an expert panel. Thornton, NLR., Black, W., Bognar, A., et al.[2023]

Ketamine is a rapid-acting antidepressant that can show effects within hours and sustain relief from Major Depressive Disorder (MDD) symptoms for up to 7 days, representing a significant advancement for treatment-resistant depression.

The chapter discusses ketamine's safety and efficacy, including its potential to reduce suicidal thoughts and its interaction with psychotherapy, highlighting its role as a novel therapeutic option for individuals who do not respond to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Major Depressive Disorder. Costi, S.[2023]

Intranasal esketamine, when combined with SSRIs or SNRIs, has been shown to be more effective than using these antidepressants alone for treating resistant major depressive disorder, based on a systematic review of four high-quality randomized controlled trials.

Esketamine is recommended as a second-line treatment option for adults aged 18 to 74 who have not responded to at least two previous antidepressant treatments, but caution is advised in its use, particularly regarding patients with suicidal ideation or psychotic depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of esketamine in resistant major depressive disorder: A systematic review of the literature]. Mungo, A., Hein, M.[2022]

Intranasal esketamine significantly improves response and remission rates in patients with major depressive disorder (MDD) compared to placebo, with effects starting as early as 2 hours and lasting for at least 28 days, based on a meta-analysis of 4 randomized controlled trials involving 708 patients.

While intranasal esketamine shows rapid antidepressant effects, it is associated with a higher rate of discontinuation due to intolerability, indicating a need for further research on its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive intranasal esketamine for major depressive disorder: A systematic review of randomized double-blind controlled-placebo studies. Zheng, W., Cai, DB., Xiang, YQ., et al.[2022]

A review of 10 clinical trials on esketamine for resistant depression found that 90% of the trials had low-quality reporting of adverse events (AEs), indicating significant gaps in safety data.

The study revealed that 41.5% of serious AEs and 39% of non-serious AEs were not reported in published articles, particularly psychiatric and cardiovascular events, suggesting that the assessment of esketamine's risk-benefit balance may be inaccurate due to incomplete harm reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of harms in clinical trials of esketamine in depression: a systematic review. Taillefer de Laportalière, T., Jullien, A., Yrondi, A., et al.[2023]

Esketamine combined with an antidepressant significantly improves depression symptoms in treatment-resistant patients, as shown by a meta-analysis of 701 patients, with notable reductions in MADRS and SDS scores.

The combination treatment also leads to higher response and remission rates compared to placebo, indicating its efficacy, although some minor adverse reactions may occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Esketamine Combined with Antidepressants for Treatment-Resistant Depression: A Meta-Analysis. Liu, P., Zhang, SS., Liang, Y., et al.[2022]

Esketamine has been shown to induce antidepressant effects in patients with Major Depression Disorder (MDD), based on a meta-analysis of four randomized controlled trials involving 551 patients.

However, the analysis revealed a significant increase in adverse effects compared to placebo, including nausea, dissociation, dizziness, and sedation, indicating that while esketamine can be effective, it also carries specific risks that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials. Yang, S., Wang, J., Li, X., et al.[2022]

In a study of 362 patients with major depressive disorder and active suicidal ideation, those receiving esketamine nasal spray plus standard care showed a significantly higher response rate (63.9% vs 48.0%) compared to those receiving placebo at 4 weeks, indicating its efficacy even for patients who did not respond initially.

Patients who did not show improvement within the first week still had a good chance of achieving response and remission by the end of the 4-week treatment, suggesting that esketamine can be beneficial for those who may not respond quickly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment response to esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior without evidence of early response: a pooled post hoc analysis of ASPIRE. Turkoz, I., Lopena, O., Salvadore, G., et al.[2022]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

Esketamine (ESK) nasal spray combined with standard care significantly reduced the time to remission in adults with major depressive disorder (MDD) and acute suicidal ideation, with median times of 15 days for ESK compared to 23 days for placebo.

Patients receiving ESK also had a higher proportion achieving remission by Day 25 (65.2% vs. 55.5%) and spent more days in remission (27.1% vs. 8.3%), highlighting its efficacy in treating severe depression with suicidality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality. Fu, DJ., Zhang, Q., Shi, L., et al.[2023]

Intranasal esketamine (ESK) has been shown to provide significant and rapid improvement in patients with treatment-resistant depression (TRD) compared to placebo, making it a promising option for those who do not respond to traditional antidepressants.

While esketamine is effective, it can cause common side effects such as dizziness, vertigo, headache, and increased blood pressure, highlighting the need for further long-term studies to fully understand its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esketamine: a glimmer of hope in treatment-resistant depression. Kaur, U., Pathak, BK., Singh, A., et al.[2021]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04103892

NCT04103892 | A Study of CLE-100 (Oral Esketamine) in ...

The clinical trial is a Phase 2, double-blind, randomized, placebo controlled study in Major Depressive Disorder (MDD) participants currently treated with ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40601310/

Esketamine Monotherapy in Adults With Treatment ...

Main outcomes and measures: Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 28 (primary efficacy end ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2772598724000230

A real-world study examining the impact of esketamine ...

This study describes changes in quality of life, depressive symptoms and productivity in participants treated with esketamine in real-world settings.

4.

clexio.com

clexio.com/pipeline/cle-100/

CLE-100

This study assessed the efficacy and safety profile of CLE-100 in subjects with Major Depressive Disorder who have had inadequate response to standard ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12205164/

Oral esketamine for patients with severe treatment-resistant ...

Oral esketamine treatment improved depressive symptom severity on the HDRS17 from 21.2 to 15.8 (p < 0.001). MCID, response, and remission rates were 47.1%, 26.8 ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38476783/

Exploring Esketamine's Therapeutic Outcomes as an FDA ...

Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder ...

7.

spravatohcp.com

spravatohcp.com/mdsi-data-dosing/

MDSI Dosing & Safety Data

Limitations of Use: The effectiveness of SPRAVATO® in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated.