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.
12345What 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.
13467Is 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.
12346Eligibility 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
+8 more
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.
+9 more
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: PF-07038124Experimental Treatment1 Intervention
PF-07038124 0.02% ointment once daily for 8 weeks
Group II: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Icahn School of Medicine at Mount SinaiNew York, NY
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Who Is Running the Clinical Trial?
Icahn School of Medicine at Mount SinaiLead Sponsor
PfizerIndustry Sponsor
References
Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. [2019]The phosphodiesterase (PDE) 4 is the predominant cyclic AMP degrading enzyme in a variety of inflammatory cells including eosinophils, neutrophils, macrophages, T cells and monocytes. In addition, this enzyme is expressed in non-immune cells such as keratinocytes and fibroblasts. Highly selective PDE4 inhibitors are currently under evaluation for the treatment of asthma and/or chronic obstructive pulmonary disease. Due to the broad anti-inflammatory/immuno-modulatory action of PDE4 inhibitors, it has been proposed that PDE4 inhibitors might also be efficacious for skin disorders such as atopic dermatitis. Consequently, PDE4 inhibitors including cilomilast and AWD 12-281 have been tested in several models of allergic and irritant skin inflammation. These PDE4 inhibitors displayed strong anti-inflammatory action in models of allergic contact dermatitis in mice, in the arachidonic acid induced skin inflammation in mice and in ovalbumin sensitised guinea pigs. The determination of cytokines in skin homogenates revealed that both Th1 as well as Th2 cytokines are suppressed by PDE4 inhibitors, indicating an anti-inflammatory activity in both the Th2 dominated acute phase as well as the Th1 dominated chronic phase of atopic dermatitis. Due to the suppression of Th1 cytokines, activity can also be expected in psoriasis. Results of early clinical trials with both topically (cipamfylline, CP80,633) and systemically (CC-10004) active PDE4 inhibitors demonstrated efficacy in atopic dermatitis and in the case of CC-10004, also in psoriasis. AWD 12-281 (GW 842470) is currently under clinical evaluation for the topical treatment of atopic dermatitis. Results concerning clinical efficacy of this potent and selective PDE4 inhibitor are anxiously awaited.
Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases. [2021]Agents which increase intracellular cyclic adenosine monophosphate (cAMP) may have an antagonistic effect on pro-inflammatory molecule production so that inhibitors of the cAMP degrading phosphodiesterases have been identified as promising drugs in chronic inflammatory disorders. Although many such inhibitors have been developed, their introduction in the clinic has been hampered by their narrow therapeutic window with side effects such as nausea and emesis occurring at sub-therapeutic levels. The latest generation of inhibitors selective for phosphodiesterase 4 (PDE4), such as apremilast and roflumilast, seems to have an improved therapeutic index. While roflumilast has been approved for the treatment of exacerbated chronic obstructive pulmonary disease (COPD), apremilast shows promising activity in dermatological and rheumatological conditions. Studies in psoriasis and psoriatic arthritis have demonstrated clinical activity of apremilast. Efficacy in psoriasis is probably equivalent to methotrexate but less than that of monoclonal antibody inhibitors of tumour necrosis factor (TNFi). Similarly, in psoriatic arthritis efficacy is less than that of TNF inhibitors. PDE4 inhibitors hold the promise to broaden the portfolio of anti-inflammatory therapeutic approaches in a range of chronic inflammatory diseases which may include granulomatous skin diseases, some subtypes of chronic eczema and probably cutaneous lupus erythematosus. In this review, the authors highlight the mode of action of PDE4 inhibitors on skin and joint inflammatory responses and discuss their future role in clinical practice. Current developments in the field including the development of topical applications and the development of PDE4 inhibitors which specifically target the subform PDE4B will be discussed.
Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models. [2013]Due to the broad anti-inflammatory and immunomodulatory actions of phosphodiesterase (PDE) 4 inhibitors, it has been proposed that PDE4 inhibitors might be efficacious for skin disorders such as atopic dermatitis. KF66490 is a newly developed PDE4 inhibitor that inhibits PDE4B (IC(50)=220 nM) and the production of tumor necrosis factor (TNF)-alpha by mouse peritoneal exudated cells stimulated with lipopolysaccharide (IC(50)=855 nM). To evaluate efficacy of KF66490 in atopic dermatitis (AD) models, on skin inflammation induced by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) on ear in BALB/c mice and on spontaneously AD-like skin diseases in NC/Nga mice. BALB/c mice were sensitized with 0.3% w/v TNCB applied to the ear on day-7, followed by application three times a week from days 0 to 21. NC/Nga mice spontaneously developed dermatitis symptoms under conventional conditions. Test compounds were administered orally once daily during experiments. In the TNCB-induced dermatitis model, KF66490 significantly inhibited the increase in ear thickness and interleukin (IL)-4 and IL-1beta levels in the ear. Histopathological and immunohistochemical analysis revealed that KF66490 significantly inhibited the proliferation of fibroblasts and CD3-positive T cells infiltration into the ear. In addition, KF66490 significantly suppressed the development of dermatitis in NC/Nga mice on all observation days, except for 5 and 6 weeks after the first dose. Furthermore, KF66490 produced less potent emetic effects than the first generation PDE4 inhibitor, rolipram. The present results suggest that KF66490 has excellent potential as an oral medicine for the treatment of atopic dermatitis.
Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study. [2018]Phosphodiesterase type 4 (PDE4) inhibition is a well-known anti-inflammatory mechanism. However, the clinical use of PDE4 inhibitors has been compromised by the occurrence of mechanism-associated adverse reactions, which often limit the maximum tolerated dose. To minimize systemic exposure, a topically active PDE4 inhibitor with low transdermal bioavailability could be clinically useful. The purpose of this study was to evaluate the efficacy of a novel topical PDE4 inhibitor, E6005, in patients with atopic dermatitis.
Trial of Roflumilast Cream for Chronic Plaque Psoriasis. [2020]Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.
DRM02, a novel phosphodiesterase-4 inhibitor with cutaneous anti-inflammatory activity. [2021]Chronic inflammatory skin disorders are frequently associated with impaired skin barrier function. Selective phosphodiesterase-4 (PDE4) inhibition constitutes an effective therapeutic strategy for the treatment of inflammatory skin diseases. We now report the pharmacological anti-inflammatory profile of DRM02, a novel pyrazolylbenzothiazole derivative with selective in vitro inhibitory activity toward PDE4 isoforms A, B and D. DRM02 treatment of cultured primary human and mouse epidermal keratinocytes interfered with pro-inflammatory cytokine production elicited by interleukin-1α and tumor necrosis factor-α. Similarly, DRM02 inhibited the production of pro-inflammatory cytokines by human peripheral blood mononuclear cells ex vivo and cultured THP-1 monocyte-like cells, with IC50 values of 0.6-14 µM. These anti-inflammatory properties of DRM02 were associated with dose-dependent repression of nuclear factor-κB (NF-κB) transcriptional activity. In skin inflammation in vivo mouse models, topically applied DRM02 inhibited the acute response to phorbol ester and induced Th2-type contact hypersensitivity reactivity. Further, DRM02 also decreased cutaneous clinical changes and expression of Th17 immune pathway cytokines in a mouse model of psoriasis evoked by repeated topical imiquimod application. Thus, the overall pharmacological profiling of the PDE4 inhibitor DRM02 has revealed its potential as a topical therapy for inflammatory skin disorders and restoration of skin homeostasis.
The effect of the PDE-4 inhibitor (cipamfylline) in two human models of irritant contact dermatitis. [2014]New therapeutic approaches have to be considered in the treatment of irritant contact dermatitis (ICD). Recently, phosphodiesterase 4 (PDE-4) inhibitors have been introduced as nonsteroidal, antiinflammatory agents. These agents inhibit the secretion of the cytokines thought to be involved in the pathogenesis of ICD. We investigated the effect of a new selective PDE-4 inhibitor (cipamfylline) in human models using single and repeated exposures to an irritant in a blind, randomized pilot study with healthy volunteers. We compared the effect of cipamfylline ointment with a strong corticosteroid (betamethasone-17-valerate) and with a placebo ointment.