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: Unknown

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a double-blind, vehicle-controlled clinical trial. The study will take place at Icahn School of Medicine at Mount Sinai. The study will include 33-39 adult subjects with moderate-to-severe-Seborrheic dermatitis (SD) as well as 33-39 adult subjects with moderate-to-severe papulopustular rosacea (PPR). Subjects will be randomized 2:1 to receive study drug or placebo. Enrolled subjects will apply topical PF-07038124 0.02% ointment once daily for 8 weeks. They will return for visits at weeks 4, 8, and 12 following study treatment initiation for repeat clinical assessments, medication reviews, tape-strip, blood and urine sample collections, and monitoring for adverse events.

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.

What data supports the idea that PDE4 Inhibitor for Skin Conditions (also known as: PF-07038124, PF-07038124) is an effective treatment?

The available research shows that PDE4 inhibitors have strong anti-inflammatory effects, which help in treating skin conditions like atopic dermatitis and psoriasis. For example, studies have shown that PDE4 inhibitors can reduce skin inflammation in animal models and have demonstrated effectiveness in early clinical trials for atopic dermatitis and psoriasis. Compared to other treatments, PDE4 inhibitors like apremilast have shown similar effectiveness to methotrexate for psoriasis, although they are less effective than some advanced treatments like TNF inhibitors. Additionally, newer PDE4 inhibitors like KF66490 have shown potential with fewer side effects, making them promising options for treating skin conditions. ^{1 2 3 4 5}

What safety data exists for PDE4 inhibitors used in skin conditions?

The safety data for PDE4 inhibitors in skin conditions indicates that these treatments have been evaluated for their anti-inflammatory effects in various models of skin inflammation, such as atopic dermatitis and psoriasis. Studies have shown that PDE4 inhibitors like cilomilast, AWD 12-281, KF66490, E6005, DRM02, and cipamfylline have demonstrated efficacy in reducing inflammation and cytokine production in both animal models and early human trials. However, the clinical use of PDE4 inhibitors has been limited by mechanism-associated adverse reactions, which can restrict the maximum tolerated dose. Some newer PDE4 inhibitors, like KF66490, have shown reduced emetic effects compared to earlier versions like rolipram. Topical formulations, such as E6005 and DRM02, aim to minimize systemic exposure and associated side effects, potentially offering safer alternatives for treating inflammatory skin disorders. ^{1 3 4 6 7}

Is the drug PF-07038124 a promising treatment for skin conditions?

Yes, PF-07038124, a PDE4 inhibitor, is promising for skin conditions because PDE4 inhibitors have shown strong anti-inflammatory effects in treating skin disorders like atopic dermatitis and psoriasis. They work by reducing inflammation and immune responses, which are key factors in these conditions. ^{1 2 3 4 6}

Research Team

Benjamin Ungar

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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.

I do not have active hepatitis B, C, or HIV.

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Trial of Roflumilast Cream for Chronic Plaque Psoriasis. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

DRM02, a novel phosphodiesterase-4 inhibitor with cutaneous anti-inflammatory activity. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

The effect of the PDE-4 inhibitor (cipamfylline) in two human models of irritant contact dermatitis. [2014]