PDE4 Inhibitor for Skin Conditions

Overseen By Giselle Singer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: PDE4 inhibitors, Topical treatments, Immunosuppressives, Biologics

Disqualifiers: Skin infections, Uncontrolled diseases, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new ointment, PF-07038124 (a PDE4 inhibitor), for treating moderate-to-severe skin conditions such as seborrheic dermatitis (SD) and papulopustular rosacea (PPR). Participants will use either the ointment or a placebo (a treatment with no active drug) to evaluate its effectiveness over eight weeks. The trial seeks volunteers with significant SD affecting the face or PPR with at least 12 inflammatory bumps. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

Yes, you must stop all treatments for SD and PPR from screening through study completion, except for the study drug. Additionally, you cannot use certain topical treatments within 2 weeks of baseline and systemic non-biologic immunosuppressive medications within 4 weeks of study initiation. Systemic biologic immunosuppressive medications must be stopped 12 weeks before baseline.

Is there any evidence suggesting that PF-07038124 is likely to be safe for humans?

Research shows that PF-07038124, a topical cream, is generally safe for use. Earlier studies involving individuals with skin conditions such as atopic dermatitis and plaque psoriasis demonstrated that this treatment was effective and safe. It outperformed a placebo, with only a few mild side effects reported.

However, studies on similar treatments, known as PDE4 inhibitors, have shown a small risk of minor side effects like pain, though these were uncommon. As this trial is in an early stage, researchers are still investigating the safety of PF-07038124 for other conditions, such as seborrheic dermatitis and papulopustular rosacea. Participants in the study will be monitored for any side effects. ^{1 2 3 4 5}

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

Unlike the standard treatments for inflammatory skin conditions, which often include corticosteroids or topical calcineurin inhibitors, the PF-07038124 ointment is unique because it targets a different pathway. This treatment is a PDE4 inhibitor, which means it works by blocking a specific enzyme that plays a key role in the inflammatory process. Researchers are excited about PF-07038124 because it offers a novel mechanism of action that could potentially provide effective relief with a lower risk of side effects commonly associated with traditional treatments. Additionally, as a once-daily ointment, it offers a simple and convenient application for users.

What evidence suggests that this treatment might be an effective treatment for skin conditions?

Research shows that PF-07038124, a skin cream tested in this trial, may help treat certain skin conditions. Studies have found that this cream can reduce symptoms in people with atopic dermatitis and plaque psoriasis. In these studies, PF-07038124 improved skin health more effectively than a placebo. The cream works by blocking an enzyme called phosphodiesterase 4 (PDE4), which causes inflammation, thereby soothing irritated skin. Although this is early evidence, it suggests that PF-07038124 might also help with conditions like seborrheic dermatitis and papulopustular rosacea. ^{2 6 7 8 9}

Who Is on the Research Team?

Benjamin Ungar

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults over 18 with moderate-to-severe Seborrheic Dermatitis (SD) or Papulopustular Rosacea (PPR), who have specific severity scores and agree to avoid other treatments during the study. Participants must use effective contraception, be in good health, and not have used certain medications recently.

Inclusion Criteria

I am willing to use birth control to prevent pregnancy or fathering a child.

My skin condition is severe with significant facial involvement.

The female subject's chosen form of contraception must be effective by the time the female subject is enrolled into the study

Exclusion Criteria

I have not had a skin infection in the last 2 weeks.

My skin condition is mild with less than 12 inflamed spots and no facial involvement.

History of adverse systemic or allergic reactions to any component of the study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants apply topical PF-07038124 0.02% ointment once daily for 8 weeks

8 weeks

3 visits (in-person) at weeks 4, 8, and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at week 12

What Are the Treatments Tested in This Trial?

Interventions

• PF-07038124

Trial Overview The trial is testing PF-07038124 ointment against a placebo for SD and PPR. It's double-blind, meaning neither participants nor researchers know who gets the real treatment. Subjects apply it daily for 8 weeks with follow-ups at weeks 4, 8, and 12.

How Is the Trial Designed?

Group I: PF-07038124 Experimental Treatment 1 Intervention

PF-07038124 0.02% ointment once daily for 8 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo Ointment

PF-07038124 is already approved in United States for the following indications:

Approved in United States as PF-07038124 for:

• Seborrheic dermatitis
• Papulopustular rosacea

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

DRM02, a selective phosphodiesterase-4 (PDE4) inhibitor, effectively reduces inflammation in skin disorders by decreasing pro-inflammatory cytokine production in both human and mouse skin cells, with IC50 values ranging from 0.6 to 14 µM.

In mouse models, topical application of DRM02 not only inhibited acute skin inflammation but also reduced symptoms and cytokine expression associated with psoriasis, suggesting its potential as a therapeutic option for restoring skin health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DRM02, a novel phosphodiesterase-4 inhibitor with cutaneous anti-inflammatory activity. Hunt, DWC., Ivanova, IA., Dagnino, L.[2021]

PDE4 inhibitors, which target a key enzyme involved in inflammation, have shown strong anti-inflammatory effects in various models of skin disorders, including atopic dermatitis and psoriasis, suggesting their potential as effective treatments.

Early clinical trials of PDE4 inhibitors, both topical and systemic, have demonstrated efficacy in treating atopic dermatitis, with ongoing evaluations for their use in psoriasis, indicating a promising avenue for managing these skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Bäumer, W., Hoppmann, J., Rundfeldt, C., et al.[2019]

KF66490, a new phosphodiesterase 4 (PDE4) inhibitor, showed significant efficacy in reducing skin inflammation in mouse models of atopic dermatitis, effectively decreasing ear thickness and inflammatory cytokine levels.

Compared to older PDE4 inhibitors, KF66490 demonstrated a better safety profile with fewer emetic effects, indicating its potential as a more tolerable oral treatment option for atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models. Harada, D., Takada, C., Nosaka, Y., et al.[2013]

Phosphodiesterase 4 (PDE4) inhibitors, like apremilast and roflumilast, show promise in treating chronic inflammatory disorders by increasing intracellular cAMP levels, which can reduce pro-inflammatory molecule production.

Apremilast has demonstrated clinical efficacy in treating psoriasis and psoriatic arthritis, with effectiveness comparable to methotrexate but less than that of TNF inhibitors, indicating its potential as a valuable option in anti-inflammatory therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases. Wittmann, M., Helliwell, PS.[2021]

A study involving 40 adult patients with atopic dermatitis demonstrated that the topical PDE4 inhibitor E6005 significantly reduced lesion severity, particularly at the 0.2% concentration, with a mean percent change of -54.30%.

E6005's targeted application minimizes systemic exposure, potentially reducing the adverse reactions commonly associated with oral PDE4 inhibitors, making it a promising treatment option for atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study. Ohba, F., Matsuki, S., Imayama, S., et al.[2018]

In a pilot study involving 21 healthy volunteers, the strong corticosteroid betamethasone-17-valerate significantly reduced symptoms of irritant contact dermatitis (ICD) compared to the PDE-4 inhibitor cipamfylline and a placebo, indicating its superior efficacy in managing ICD.

The study did not find significant differences in the effectiveness of cipamfylline compared to placebo in treating acute ICD, suggesting that further clinical studies are necessary to fully evaluate the potential of PDE-4 inhibitors in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of the PDE-4 inhibitor (cipamfylline) in two human models of irritant contact dermatitis. Kucharekova, M., Hornix, M., Ashikaga, T., et al.[2014]

In a phase 2b trial involving 331 adults with plaque psoriasis, roflumilast 0.3% cream was found to be significantly more effective than a placebo, with 28% of patients achieving clear or almost clear skin at week 6 compared to only 8% in the vehicle group.

Roflumilast cream also showed a substantial reduction in psoriasis severity, with a mean change in the Psoriasis Area and Severity Index (PASI) score of -50.0% for the 0.3% group, indicating its potential as a topical treatment for psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of Roflumilast Cream for Chronic Plaque Psoriasis. Lebwohl, MG., Papp, KA., Stein Gold, L., et al.[2020]

Citations

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Efficacy and Safety of PF-07038124 in Patients With Atopic ... This phase 2a randomized clinical trial assesses the efficacy, safety, tolerability, and pharmacokinetics of topical PF-07038124 in patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10733847/

Efficacy and Safety of PF-07038124 in Patients With Atopic ... Topical PF-07038124 is an effective and well-tolerated treatment for AD and plaque psoriasis. This phase 2a randomized clinical trial assesses ...

3. ajmc.com ajmc.com/view/topical-pf-07038124-demonstrates-superior-efficacy-in-patients-with-ad-plaque-psoriasis

Topical PF-07038124 Demonstrates Superior Efficacy in ... A topical therapy, PF-07038124 0.01%, administered once daily was more effective than the vehicle control in patients with atopic dermatitis (AD) ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/03000605251333654

Effectiveness and safety of topical phosphodiesterase 4 ... Our meta-analysis revealed that children with atopic dermatitis treated with phosphodiesterase 4 inhibitors experienced higher remission rates ...

5. finance.yahoo.com finance.yahoo.com/news/arcutis-announces-publication-positive-long-130000943.html

Arcutis Announces Publication of Positive Long-Term ... ZORYVE foam 0.3% was safe, well-tolerated, and demonstrated durable and continuously improving efficacy in the treatment of seborrheic ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38117526/

Efficacy & Safety of PF-07038124 for Atopic Dermatitis/Psoriasis Topical PF-07038124 was well tolerated and demonstrated superior efficacy compared with vehicle in patients with mild to moderate AD and plaque psoriasis.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0011393X22000182

Safety of Topical PDE4 Inhibitors for Atopic Dermatitis In studies with low risk of bias, PDE4 inhibitors had a statistically significant risk of producing pain and reduced occurrence of atopic dermatitis ...

8. jidonline.org jidonline.org/article/S0022-202X(24)01574-4/fulltext

LB944 The efficacy and safety of multiple dose levels ... The efficacy and safety of PF-07038124, a potent phosphodiesterase-4 (PDE4) inhibitor was assessed in participants with atopic dermatitis (AD) and plaque ...

9. medicalaffairs.arcutis.com medicalaffairs.arcutis.com/investigational-therapies/pde4-inhibitor/

PDE4 Inhibitor Overview | Arcutis Biotherapeutics Medical Affairs PDE4 is an enzyme that contributes to immune-mediated dermatologic conditions. Increases inflammatory mediators Disrupts skin barrier balance Increases ...