Clobetasol Topical Oil for Children With Moderate to Severe Atopic Dermatitis

This study is a multicenter, open-label study designed to evaluate the HPA axis suppression potential and systemic exposure to clobetasol, when administered as Clobetasol Topical Oil in pediatric subjects, under conditions consistent with anticipated clinical use and under conditions designed to maximize the potential for drug absorption in subjects with moderate to severe AD. The study will consist of three successively younger pediatric cohorts, as safety data allow:

* Cohort 1: ≥12 to <18 years;
* Cohort 2: ≥6 to <12 years; and
* Cohort 3: ≥2 to <6 years. Enrollment into each successively younger pediatric cohort will proceed only after the preceding cohort has been completed and safety and exploratory data (including adverse events \[AEs\], tolerability assessments, clinical laboratory results, and the percentage of subjects with HPA axis suppression) have been reviewed and agreed to be acceptable for progression to the next cohort. Enrollment into Cohorts 2 and 3 will proceed only if the percentage of subjects with HPA axis suppression in Cohorts 1 and 2, respectively, is ≤40%. HPA axis suppression is defined as a cortisol concentration ≤18 µg/100 mL at approximately 30 minutes after stimulation with cosyntropin.

• Clobetasol propionate 0.05% Topical Oil (Drug), also known as clobetasol propionate topical solution: thin film application of the oil twice daily

Primary outcomes

• Number of Participants With HPA Axis Suppression - Serum Cortisol Concentration (Cortrosyn Stimulation Test) [day 0 and day 15.]: 30-minute Post-stimulation cortisol level ≤18 µg/100 mL at Day 0 means subject is not enrolled; 30-minute Post-stimulation cortisol level ≤18 µg/100 mL at end of treatment (Day 15) means subject had suppression.
• Adverse Events, Including Treatment Emergent Adverse Events (TEAEs) [Days 0, 1, 8 and 15]: number of events and percentage of subjects with AEs including TEAEs

Other outcomes

• ISGA Category [Days 0, 1, 8 and 15 Efficacy assessment, including ISGA, was not performed due to premature termination of the study.]: ISGA results will be summarized at each visit as: 1. number and percentage of subjects in each ISGA category 2. number and percentage of subjects with an ISGA score of either 0 or 1 (clear or almost clear) 3. number and percentage of subjects with an ISGA improvement of at least 2 grades from Baseline to each post-baseline evaluation 4. number and percentage of subjects with an ISGA score of either 0 or 1 (clear or almost clear) and an improvement of at least 2 grades from Baseline to each post-Baseline evaluation
• Assessment of Burning/Stinging, Skin Atrophy, Striae, Folliculitis, and Telangiectasias (Tolerability Parameters). [Days 1, 8 and 15]: The subject will rate the sensation of burning/stinging within the past 24 hours as none (0), mild (1), moderate (2) or severe (3), and the Investigator will assess skin atrophy, striae, folliculitis, and telangiectasias, as absent (0) or present (1).

Sex: All, ages: 2 Years to 18 Years

Inclusion Criteria:

* Male or female subjects in good general health confirmed by medical history.
* Subjects with a clinical diagnosis of AD (according to the criteria of Hanifin and Rajka) of moderate to severe intensity (ISGA score of 3 or 4) involving ≥25% to ≤50% of total BSA located within treatable areas (Cohort 1), or ≥35% to ≤50% of total BSA located within treatable areas (Cohorts 2 and 3), with treatable areas including all but the face, axillae, groin, and scalp.
* Subjects with a normally functioning HPA axis, defined as a prestimulation serum cortisol level >5 µg/100 mL, and a response to cosyntropin stimulation to >18 µg/100 mL (after approximately 30 minutes); both blood draws for this test should be performed in the morning, if possible
* Female subjects of childbearing potential must have a negative urine pregnancy test, must not be breastfeeding, and must agree to use an acceptable form of birth control for the duration of the study. Female subjects of childbearing potential are defined as all female subjects who have reached menarche and are not two years postmenopausal or who have reached menarche and have not had a hysterectomy, bilateral tubal ligation, and/or complete bilateral oophorectomy

Exclusion Criteria:

* Subjects who do not have a normally functioning HPA axis (as defined in the inclusion criteria).
* Subjects with an abnormal sleep schedule or who work at night.
* Subjects who have used topical dermal corticosteroids or topical immunomodulators (e.g., tacrolimus or pimecrolimus) within 3 weeks before Day 1, and subjects who are using any systemic medication known to affect cortisol levels or HPA axis integrity, systemic corticosteroids, an acute systemic course of corticosteroids, and/or any biological medication within 30 days before Day 1.
* Subjects with concomitant medical or dermatologic disorders (neurodermatitis, skin atrophy, striae, telangiectasia, etc.) that may interfere with study objectives and/or evaluations.
* Subjects with active skin infection.
* Subjects with any known significant endocrinological disorder that may require prohibited treatment, any known underlying disease that the investigator deems uncontrolled and poses a safety risk for the subject while participating in the study, known sensitivity to any ingredient of the study preparation, or a history of adverse responses to topical or systemic steroid therapy.
* Subjects who are pregnant or nursing.
* Subjects who have used bleach baths, phototherapy, and/or tanning beds, and/or who have had excessive sun exposure within 1 week before Day 1 and/or are planning to use any of these during the study.
* Subjects who have participated in a clinical drug or device research study and/or used any investigational treatment within the last 30 days before Day

Participant flow

Outcome results

• Number of Participants With HPA Axis Suppression - Serum Cortisol Concentration (Cortrosyn Stimulation Test) (Primary), Count of participants, Participants: Clobetasol Propionate Topical Oil in Cohort 1 0; Clobetasol Propionate Topical Oil in Cohort 2 0; Clobetasol Propionate Topical Oil in Cohort 3 0
• Adverse Events, Including Treatment Emergent Adverse Events (TEAEs) (Primary), Count of participants, Participants: Clobetasol Propionate Topical Oil in Cohort 1 8; Clobetasol Propionate Topical Oil in Cohort 2 0; Clobetasol Propionate Topical Oil in Cohort 3 0
• ISGA Category (Other pre specified)
• Assessment of Burning/Stinging, Skin Atrophy, Striae, Folliculitis, and Telangiectasias (Tolerability Parameters). (Other pre specified), Count of participants, Participants: Clobetasol Propionate Topical Oil in Cohort 1 8; Clobetasol Propionate Topical Oil in Cohort 2 ; Clobetasol Propionate Topical Oil in Cohort 3

Adverse events

Time frame: AEs were collected at start of study to termination of the study, approximately 6 months.

Limitations and caveats: The study was terminated early due to the COVID pandemic with very low subject enrollment. Due to the small number of subjects that completed when the study was prematurely terminated, pharmacokinetic, exploratory, sensitivity, as well as some safety analyses was not completed under the SAP.

• Study Protocol (PDF, 2019-01-28)
• Statistical Analysis Plan (PDF, 2020-08-04)

• Rosario G Ramirez, MD, Study director, Hill Dermaceuticals, Inc.