Apremilast for Erythema Multiforme

(AEM Trial)

Overseen By Joshua S Bryer, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Robert Micheletti

Must not be taking: Immunosuppressive medications

Disqualifiers: Uncontrolled major diseases, Psychiatric illness, Substance abuse, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called apremilast (also known as Otezla) to determine its effectiveness for people with chronic erythema multiforme (EM), which causes painful skin and mouth sores and resists current treatments. The goal is to see if apremilast can reduce pain and the number of flare-ups over six months. Suitable participants have experienced at least two flare-ups in the past six months, despite using standard treatments like valacyclovir or immune-related medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude those using immunosuppressive medications for other diseases. It's best to discuss your current medications with the study team.

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

Research has shown that apremilast is generally safe. Studies have found that people with conditions like psoriasis and Bechet's Disease, which are similar to erythema multiforme (EM), usually tolerate it well. Most side effects were mild, such as headaches or nausea, and serious side effects were rare.

The FDA has already approved apremilast for Bechet's Disease, indicating it has passed strict safety tests for that condition. This suggests it might also be safe for treating chronic EM. However, since this trial is in an early stage, monitoring how patients with EM react to the treatment is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for erythema multiforme, which typically involve corticosteroids and antihistamines to manage symptoms, Apremilast works by targeting a different pathway. Apremilast is a small molecule that inhibits the enzyme phosphodiesterase 4 (PDE4), which plays a role in inflammatory processes. By reducing inflammation through this novel mechanism, Apremilast could offer a new way to manage erythema multiforme, potentially with fewer side effects than traditional therapies. Researchers are excited about its potential to provide more effective relief for patients who may not respond well to conventional treatments.

What evidence suggests that apremilast might be an effective treatment for erythema multiforme?

Research has shown that apremilast might help treat conditions like erythema multiforme (EM). It is already used for Bechet's Disease, which also affects the skin and mouth. Some studies suggest that apremilast could benefit individuals with recurring EM who haven't improved with other treatments, such as antiviral drugs and immune system suppressants. Although specific data on EM is limited, its success in similar conditions offers hope for its potential effectiveness. Overall, there is reason to be optimistic about apremilast as a treatment option for EM. ^{1 4 6 7 8}

Who Is on the Research Team?

Robert G Micheletti, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults aged 18-89 with chronic erythema multiforme (EM) that's resistant to standard treatments can join this trial. They must have had multiple EM flares in the past year, be generally healthy, and willing to follow study procedures for 6 months. Pregnant or breastfeeding individuals, those with serious uncontrolled conditions, a history of certain psychiatric issues or substance abuse cannot participate.

Inclusion Criteria

I am not pregnant and will use birth control during and after the study.

I have been diagnosed with erythema multiforme by a dermatologist.

Willing and able to provide personally signed and dated informed consent form

Exclusion Criteria

I haven't taken any experimental drugs recently.

I cannot take Apremilast due to health risks listed in its guidelines.

Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if they were to participate in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apremilast for 6 months to evaluate changes in pain and EM flares

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in pain and flare frequency

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Apremilast

Trial Overview The trial is testing Apremilast (Otezla), which is already used for a similar condition called Bechet's Disease. Participants will take Apremilast for six months to see if it reduces pain and the number of EM flares compared to their experiences before starting treatment.

Apremilast is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Otezla for:

• Psoriatic arthritis
• Plaque psoriasis
• Behçet’s disease

Approved in European Union as Otezla for:

• Psoriatic arthritis
• Plaque psoriasis
• Behçet’s disease

Approved in Canada as Otezla for:

• Psoriatic arthritis
• Plaque psoriasis

Approved in Japan as Otezla for:

• Psoriatic arthritis
• Plaque psoriasis

Who Is Running the Clinical Trial?

Robert Micheletti

Lead Sponsor

Trials

1

Recruited

8+

Published Research Related to This Trial

Apremilast is an oral medication that inhibits PDE-4, showing efficacy in treating active psoriatic arthritis, and has received its first global approval in the USA for this condition.

The drug is also under review for approval in Canada and Europe for psoriatic arthritis and plaque psoriasis, indicating its potential as a widely used treatment option for these inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apremilast: first global approval. Poole, RM., Ballantyne, AD.[2021]

Apremilast (Otezla) is an oral medication specifically designed for adults suffering from psoriasis and psoriatic arthritis, providing a new treatment option for these conditions.

Clinical studies have demonstrated that apremilast effectively reduces the severity of psoriasis symptoms and improves joint function in patients with psoriatic arthritis, making it a valuable addition to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apremilast (Otezla): A New Oral Treatment for Adults With Psoriasis and Psoriatic Arthritis. Zerilli, T., Ocheretyaner, E.[2020]

Apremilast (Otezla®) is an effective oral medication for managing psoriasis, psoriatic arthritis, and recently approved for treating oral ulcerations in Behçet's disease, with a favorable side effect profile compared to other DMARDs.

This report highlights a rare case of laryngeal pseudotumor in a patient using apremilast for plaque psoriasis, suggesting the need for awareness of potential uncommon side effects even with well-tolerated medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pseudotumor of the Larynx: A Previously Unreported Side Effect of Apremilast. Ntouniadakis, E., Landström, F.[2021]

Apremilast is an effective oral treatment for plaque psoriasis and psoriatic arthritis, showing proven and durable efficacy in managing these conditions.

It has a favorable safety profile, requiring no specific pre-screening or ongoing laboratory monitoring, making it a convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

▼ Apremilast for psoriasis and psoriatic arthritis. [2015]

Apremilast, a phosphodiesterase 4 inhibitor, has shown complete and long-lasting resolution of erythrodermic psoriasis (EP) when used as a first-line monotherapy, suggesting it could be a promising treatment option.

Unlike traditional therapies like cyclosporine and infliximab, which have significant adverse effects, apremilast has a comparatively safer side effect profile, making it a potentially better choice for patients with EP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete resolution of erythrodermic psoriasis with first-line apremilast monotherapy. Krishnamoorthy, G., Kotecha, A., Pimentel, J.[2021]

In a small study of three patients with recurrent erythema multiforme and oral lesions, treatment with apremilast (30-60 mg daily) resulted in complete clearance of the lesions for all participants, even those who did not respond to other standard therapies.

Apremilast may be a promising treatment option for patients with recurrent erythema multiforme who have not found relief from antiviral and immunosuppressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apremilast for treatment of recurrent erythema multiforme. Chen, T., Levitt, J., Geller, L.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8467974/

Recent Updates in the Treatment of Erythema Multiforme A randomized controlled trial from 1995 outlined that the most effective approach to treatment was continuous oral antiviral therapy for a period greater than ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28329479/

Apremilast for treatment of recurrent erythema multiforme Apremilast maypresent an effective option for recurrent erythemamultiforme for patients who have failed trials antiviraland immunosuppressive therapies.

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/0976500X241303186

An In-depth Review of the Off-label Use of Apremilast ... In an individual report, apremilast was found to be helpful in treating anti-p200 pemphigoid in a 57-year-old man with concomitant psoriasis.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05875714/apremilast-for-erythema-multiforme

Apremilast for Erythema Multiforme | Clinical Research ... In this study, eligible patients will receive apremilast for 6 months of treatment so we can evaluate if there is a difference in pain and the ...

5. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/0976500X241303186

An In-depth Review of the Off-label Use of Apremilast ... Randomized controlled trials showed promise for atopic dermatitis, hidradenitis suppurativa and vitiligo. Open-label trials suggested potential benefit in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6362739/

Apremilast in Psoriasis and Beyond: Big Hopes on a Small ... In summary, apremilast is reasonably efficacious in psoriasis and PsA with potential clinical use in other inflammatory conditions. Good safety profile, ease of ...

7. otezlapro.com otezlapro.com/plaque-psoriasis/safety/

PsO Safety Profile | Otezla® (apremilast) HCP The safety profile for Otezla was studied in 7 clinical trials across mild to moderate and moderate to severe plaque psoriasis.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2589537024004887

Review Erythema multiforme Erythema multiforme is an inflammatory skin and mucosal disease mainly related to infectious agents such as Herpes simplex virus, Mycoplasma pneumoniae.