Clinical trial NCT06013371: PDE4 Inhibition in Seborrheic Dermatitis and Papulopustular Rosacea
Official title: PDE4 Inhibition in the Treatment of Seborrheic Dermatitis and Papulopustular Rosacea With PF-07038124
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Seborrheic Dermatitis
Papulopustular Rosacea
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2023-08-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized 2:1 to either drug or placebo
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: After providing consent, all subjects will be assessed for study eligibility, which includes a review of the subjects past and current medical conditions, familial medical history and detailed review of past and current medications. Subjects will also undergo a review of past topical treatments/therapies for SD or PPR, and clinical assessments (SD: clinical SD score, IGA, Peak Pruritus Numerical Rating Scale \[PP-NRS\]; PPR: inflammatory lesion count, IGA, PP-NRS).

Subjects who meet inclusion criteria for eligibility may continue with the Baseline Visit (Week 0) or can be scheduled to return for the Baseline Visit within 28 days of the Screening Visit.

At Baseline/Week 0, subjects will undergo clinical assessments (SD: clinical SD Severity Score, IGA, PP-NRS; PPR: inflammatory lesion count, IGA, PP-NRS), review of concomitant medications, standardized clinical photography, and a Dermatology Life Quality index (DLQI) questionnaire. Subsequent clinical assessments including standardized clinical photography, and questionnaire completion will be performed at follow up visits at Week 4, Week 8, and Week 12. Skin tape-strip samples will be collected for mechanistic studies (described below) at baseline (lesional and non-lesional facial skin), Week 4 (lesional facial skin), Week 8 (lesional facial skin), and Week 12 (lesional facial skin). Additional blood samples will be collected and stored at baseline and at Week 8 (or early termination, whichever is first) for potential future mechanistic analyses.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects ≥ 18 years of age at the time of signing the informed consent document.
* Subject is able to understand and voluntarily sign an informed consent document prior to participation in any study assessments or procedures.
* Subject is able to adhere to the study visit schedule and other protocol requirements.
* Diagnosis of SD and baseline IGA ≥ 3 with facial involvement
* OR
* Diagnosis of PPR, baseline IGA ≥ 3, and baseline inflammatory lesion count ≥ 12
* Subject agrees to discontinue all treatments for SD and PPR from screening through study completion aside from the study drug
* Subject is judged to be in otherwise good overall health as judged by the investigator, based on medical history, physical examination, and laboratory testing. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions).
* Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on the study drug and for at least 90 days after the last application of the study drug, male and female participants must be willing to take appropriate contraceptive measures to avoid pregnancy or fathering a child. FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:

  * Option 1: Any one of the following highly effective contraceptive methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy.
  * OR
  * Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

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

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

* Subjects with other skin diseases that would interfere with the study assessment in the opinion of the investigator.
* Active bacterial, fungal, or viral skin infection within 2 weeks from study initiation.
* Subject has clinically significant (as determined by the investigator) renal, hepatic, hematologic, intestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, immunologic, or other major uncontrolled diseases (e.g., malignancy, TB, thromboembolic events) that will affect the health of the subject during the study, or interfere with the interpretation of study results.
* Subject has previously received treatment with oral or topical PDE4 inhibitors.
* Current other topical treatments (e.g., topical corticosteroids, topical calcineurin inhibitors, topical JAK inhibitors, topical metronidazole, topical minocycline, topical ivermectin, topical azelaic acid, topical brimonidine, topical oxymetazalone, topical antihistamines, topical antibacterials) within 2 weeks of baseline.
* Use of systemic non-biologic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus, oral JAK inhibitors within 4 weeks of study initiation.
* Use of systemic biologic immunosuppressive medications, including, but not limited to inhibitors of IL-17, IL-12/23, or IL-23, TNF inhibitors, dupilumab, and abatacept within 12 weeks of baseline.
* History of adverse systemic or allergic reactions to any component of the study drug.
* Current participation in any other study with a biologic investigational medication within 6 months of baseline, or non-biologic investigational medication within 12 weeks of baseline.
* Subject who is pregnant or breast feeding.
* SD or PPR Baseline IGA \< 3; PPR inflammatory lesion count \<12; SD with no facial involvement.
* Active hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or positive HIV serology at the time of screening for subjects determined by the investigators to be at high-risk for this disease.

Primary outcomes:
measure: Number of Subjects reaching Investigator's Global Assessment (IGA) success - Seborrheic dermatitis (SD)
timeFrame: Baseline and Week 8
measure: Percent change in lesion count Papulopustular Rosacea (PPR)
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change in SD severity score at 8 weeks
timeFrame: Baseline and 8 weeks
measure: Number of patients with treatment success via IGA in PPR
timeFrame: Baseline and 8 weeks
measure: Change in Clinical Erythema - PPR
timeFrame: Baseline and 8 weeks
measure: Change in Patient assessment of erythema - PPR
timeFrame: Baseline and 8 weeks
measure: Change in Lesion count - PPR
timeFrame: Baseline, 8 weeks, 12 weeks
measure: Change in IGA Score - SD and PPR
timeFrame: Baseline, 4 and 8 weeks
measure: Percent change in IGA Score - SD and PPR
timeFrame: Baseline, 4 and 8 weeks
measure: Change in IGA Score - SD and PPR
timeFrame: Baseline and Week 12
measure: Change in Peak Pruritus Numerical Rating Scale (PP-NRS) from Baseline at Week 8
timeFrame: Baseline and Week 8
measure: Number of related adverse events
timeFrame: 12 weeks
measure: Frequency of adverse events
timeFrame: 12 weeks
measure: Severity of Adverse Events
timeFrame: 12 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Benjamin Ungar, MD
role: PRINCIPAL_INVESTIGATOR
References: