Ixekizumab for Treatment-Resistant Depression

Overseen By Sara Hameed, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: Antidepressants

Must not be taking: Biologics, Immune-suppressants

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of ixekizumab, a medication targeting the immune system, to aid individuals with treatment-resistant depression (TRD). The goal is to determine if this drug can improve symptoms for those who haven't succeeded with at least two different antidepressants. It suits individuals experiencing a major depressive episode and already on a stable dose of antidepressant medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for this trial?

No, you don't have to stop taking your current medications. In fact, you must be on a stable dose of antidepressant medication for more than 4 weeks before joining the trial.

Is there any evidence suggesting that ixekizumab is likely to be safe for humans?

Research has shown that ixekizumab, a treatment targeting the protein interleukin 17A (IL-17A), is generally well-tolerated in other conditions. Patients have continued treatment for extended periods without major safety issues. However, specific safety information for ixekizumab in treating treatment-resistant depression is not yet available. As this study is in an early research phase, it primarily focuses on learning about safety and side effects. While its use in other conditions provides some confidence in its safety, more information is needed to fully understand its safety for depression. ^{1 2 3 4 5}

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

Ixekizumab is unique because it targets a different mechanism than typical depression treatments. Most current options for depression, like SSRIs and SNRIs, focus on neurotransmitters like serotonin and norepinephrine. However, Ixekizumab is an antibody that specifically inhibits the IL-17A protein, which is part of the body's immune response and may play a role in inflammation related to depression. Researchers are excited about Ixekizumab because it offers a novel approach, potentially benefiting those who haven't responded well to standard antidepressants.

What evidence suggests that ixekizumab might be an effective treatment for treatment-resistant depression?

Research has shown that ixekizumab, a medication targeting a specific protein in the body, may benefit individuals with depression unresponsive to other treatments. One study found that about 40% of patients experienced significant improvement or remission of depression symptoms after 12 weeks of ixekizumab use. This medication also reduced inflammation levels, often associated with depression. Although primarily used for skin conditions like psoriasis, these early findings offer promise for those facing difficult-to-treat depression. ^{2 3 4 5 6}

Who Is on the Research Team?

James M Murrough, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults aged 18-65 with treatment-resistant depression, on stable antidepressant doses for over 4 weeks, and have had at least two adequate treatment trials. Participants must not be at risk of self-harm or substance abuse, pregnant or breastfeeding, and willing to use contraception.

Inclusion Criteria

I have been diagnosed with Major Depressive Disorder and am currently experiencing a major depressive episode.

Quick Inventory of Depressive Symptoms - Clinician Administered (QIDS-C) score ≥ 14

CRP level ≥ 1mg/L at screening

Exclusion Criteria

Serious and imminent risk of self-harm or violence as determined by the PI

I am not pregnant, breastfeeding, and I agree to use birth control during and for 6 months after the study.

Meets criteria for a moderate or severe substance use disorder within the past 6 months, with the exception of nicotine use disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ixekizumab 160 mg at Week 0, followed by 80 mg at Weeks 2 and 4 via subcutaneous route

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ixekizumab

Trial Overview

The trial is testing Ixekizumab, an antibody targeting IL-17A, against a placebo in patients who haven't responded well to standard depression treatments. It's designed to see if this new approach can help where other treatments haven't.

How Is the Trial Designed?

Group I: Ixekizumab Experimental Treatment 1 Intervention

Ixekizumab 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2 and 4 via subcutaneous route.

Ixekizumab is already approved in United States, European Union for the following indications:

Approved in United States as Taltz for:

• Moderate-to-severe plaque psoriasis
• Active psoriatic arthritis
• Active ankylosing spondylitis
• Active non-radiographic axial spondyloarthritis

Approved in European Union as Taltz for:

• Moderate-to-severe plaque psoriasis
• Active psoriatic arthritis
• Active ankylosing spondylitis

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

In a phase 3 study involving 363 patients with psoriatic arthritis (PsA) who had inadequate responses to one or two TNF inhibitors, ixekizumab (IXE) significantly improved disease symptoms compared to placebo, with improvements seen in ACR50 response, HAQ-DI, and other measures by week 24.

The efficacy of IXE was sustained through week 52, demonstrating its potential as an effective treatment option for patients with difficult-to-treat PsA who have not responded well to previous TNF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement from ixekizumab treatment in patients with psoriatic arthritis who have had an inadequate response to one or two TNF inhibitors. Kirkham, B., Sesin, C., Gellett, AM., et al.[2021]

In a study of 38 psoriasis patients treated with ixekizumab over an average of 32 weeks, significant clinical improvements were observed, with a mean reduction in PASI score of -7.8 and BSA score of -6.7 by week 4.

70% of patients achieved complete skin clearance (PASI 100), indicating that ixekizumab is effective for rapid and complete treatment of psoriasis, especially in patients who have not previously been treated with biologics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate-to-severe plaque psoriasis patients treated with ixekizumab: early real-world outcomes and adverse events. Gulliver, W., Penney, M., Power, R., et al.[2022]

In a phase III trial involving 1,227 patients with moderate-to-severe plaque psoriasis, continuous dosing of ixekizumab every 2 weeks (Q2W) for 52 weeks showed significantly higher efficacy compared to every 4 weeks (Q4W), with 85.9% achieving a 75% improvement in psoriasis severity versus 79.0% for Q4W.

Both dosing regimens had comparable safety profiles, indicating that the increased efficacy of the Q2W regimen did not come with a higher risk of treatment-emergent or serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P). Langley, RG., Papp, K., Gooderham, M., et al.[2019]

In a study of 66 patients with psoriasis, Ixekizumab (IXE) demonstrated high effectiveness, with 86.3% achieving a PASI 75 response and significant reductions in both PASI and DLQI scores by Week 12.

Both two-week and four-week dosing regimens of IXE were effective, allowing patients to choose a less frequent dosing schedule without significant loss of therapeutic benefits, while safety was confirmed with injection site reactions being the most common adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab four-week dosing is comparable to two-week dosing in psoriasis patients and reduces treatment costs: experience in a real-world setting over a 12-week period Li, Y., Yu, Y., Wang, Y., et al.[2022]

In a study of 23 adults with treatment-resistant depression, 91.8% reported significant improvements in emotional and daily functioning after using esketamine nasal spray (ESK) alongside an oral antidepressant (OAD).

Patients noted key benefits of ESK treatment, including its effectiveness, rapid onset of action, and a side-effect profile consistent with existing safety data, leading to high satisfaction rates (100% reported satisfaction).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study. Starr, HL., Abell, J., Larish, A., et al.[2021]

In a study involving 97 participants with treatment-resistant depression, ketamine infusions showed a 67% response rate, indicating significant antidepressant effects.

The treatment was found to be safe and well-tolerated, with only a 3.1% attrition rate and no cases of persistent adverse effects, although some participants experienced temporary side effects like drowsiness and dissociation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine safety and tolerability in clinical trials for treatment-resistant depression. Wan, LB., Levitch, CF., Perez, AM., et al.[2022]

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]

Ixekizumab is a humanized monoclonal antibody specifically designed to inhibit interleukin-17A (IL-17A), a key cytokine involved in inflammatory conditions, making it a targeted treatment for plaque psoriasis.

The approval of ixekizumab in the USA marks a significant milestone in its development, highlighting its efficacy in managing plaque psoriasis by reducing inflammation associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab: First Global Approval. Markham, A.[2018]

Patients with treatment-resistant depression (TRD) are 33% more likely to have pre-existing conditions that could lead to adverse events when using non-antidepressant augmentation therapies compared to those with non-TRD MDD.

TRD patients also face significantly higher risks of drug-drug interactions (DDIs), being 12.9 times more likely to have two or more DDIs and 6.4 times more likely to have three or more DDIs, which complicates their treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Pre-existing Conditions Relevant for Adverse Events and Potential Drug-Drug Interactions Associated with Augmentation Therapies Among Patients with Treatment-Resistant Depression. Zhdanava, M., Karkare, S., Pilon, D., et al.[2022]

Ixekizumab, an anti-interleukin 17A monoclonal antibody, was well tolerated in patients with rheumatoid arthritis over a 64-week period, with 87% of biologic-naive and 62% of TNF-IR patients completing the study.

Clinical improvements in rheumatoid arthritis symptoms, measured by various scales, were maintained or improved from Week 16 to Week 64, indicating the long-term efficacy of ixekizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Open-label Subcutaneous Ixekizumab Treatment for 48 Weeks in a Phase II Study in Biologic-naive and TNF-IR Patients with Rheumatoid Arthritis. Genovese, MC., Braun, DK., Erickson, JS., et al.[2017]

Intravenous ketamine has shown rapid antidepressant effects in patients with treatment-resistant major depressive disorder (MDD), with several studies reporting moderate to large effect sizes on depression scales.

Despite its promising rapid action and relatively well-tolerated side effects, the long-term sustainability of ketamine's antidepressant effects remains uncertain, indicating a need for further research before it can be widely recommended as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine for treatment-resistant major depressive disorder. Covvey, JR., Crawford, AN., Lowe, DK.[2013]

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Impact of Ixekizumab Treatment on Depressive Symptoms ...

12 weeks of ixekizumab therapy resulted in remission of depression for approximately 40% of patients and improved systemic inflammation as indicated by hsCRP.

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withpower.com/trial/phase-3-depressive-disorder-major-7-2021-7d5fd

Ixekizumab for Treatment-Resistant Depression

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clinicaltrials.gov

clinicaltrials.gov/study/NCT04979910

Targeting IL-17A for Treatment-Resistant Depression | ...

The proposed study aims to test ixekizumab, a monoclonal antibody (mAb) against interleukin 17A (IL-17A), in patients with treatment-resistant depression (TRD).

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karger.com

karger.com/pps/article/86/5/260/283045/Impact-of-Ixekizumab-Treatment-on-Depressive

Impact of Ixekizumab Treatment on Depressive Symptoms ...

12 weeks of ixekizumab therapy resulted in remission of depression for approximately 40% of patients and improved systemic inflammation as indicated by hsCRP.

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psychiatrist.com

psychiatrist.com/jcp/immune-targeted-therapies-depression-antidepressant-effects-monoclonal-antibodies/

Current Evidence for Antidepressant Effects of Monoclonal ...

Patients in these studies had moderate depression scores at baseline, and a greater percentage of those treated with ixekizumab met criteria ...

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pmc.ncbi.nlm.nih.gov/articles/PMC12101745/

Real-world safety assessment of Ixekizumab based on the ...

RWE complements RCTs by capturing data from clinical practice, including long-term safety, treatment persistence, and patient-reported outcomes.