Clinical trial NCT03233529: Crisaborole Ointment 2% Skin Biomarker Biopsy Study in Atopic Dermatitis
Official title: A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED STUDY, TO CHARACTERIZE THE MECHANISM OF ACTION OF CRISABOROLE OINTMENT 2%, BY EVALUATION OF EFFICACY AND CHANGES IN SKIN BIOMARKERS, IN ADULT SUBJECTS WITH MILD TO MODERATE ATOPIC DERMATITIS, WITH A 4 WEEK OPEN-LABEL EXTENSION
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dermatitis, Atopic
Keywords: atopic dermatitis
atopic eczema
eczema
topical treatment
skin diseases
phosphodiesterase-4 inhibitor
PDE-4 inhibitor
crisaborole
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-07-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study is being conducted to characterize the mechanism of action of crisaborole ointment 2%, by evaluation of efficacy and changes in key skin biomarkers in atopic dermatitis (AD) lesions treated with crisaborole ointment 2% over vehicle, in subjects with mild to moderate AD. Two identified AD skin lesions for each subject will be treated for the first 15 days, one with crisaborole ointment 2% and one with vehicle, in a blinded manner, and biopsies for biomarker analysis will be performed on the lesions. Following completion of the blinded treatment period, subjects will start the 28 day open label period during which all AD affected skin lesions will be treated with crisaborole ointment 2% twice daily.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of active atopic dermatitis (AD) with at least 6 month history prior to Screening and that has been clinically stable for 1 month.
* Investigator's Static Global Assessment (ISGA) of 2 (mild) or 3 (moderate) at Baseline.
* Body surface area (BSA) covered with AD of at least 0.5% and no more than 10% at Baseline, calculation excluding face, scalp, axilla, genitals, groin area, palms, back of the hands, and soles.
* Two lesions of AD at least 3 cm x 3 cm in size and at least 5 cm apart, with identical Lesion ISGA score of greater than/equal to 3.

Exclusion Criteria:

* Clinically infected AD or requires high potency topical corticosteroids or systemic (oral/injectable) corticosteroids to manage AD.
* History of angioedema or anaphylaxis to topical products or known sensitivity to components of crisaborole ointment 2%.
* History of cancer (except squamous or basal cell carcinoma or carcinoma in situ of the skin).
* Previous treatment with any topical or systemic PDE4 inhibitor unless stopped for the reason of lack of efficacy.

Primary outcomes:
measure: Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Key Skin Biomarker Chemokine Ligand (CCL)17 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Key Skin Biomarker Elafin/Peptidase Inhibitor 3 (PI3) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Key Skin Biomarker S100 Calcium Binding Protein A12 (S100A12) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
Secondary outcomes:
measure: Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Expression of Other Skin Biomarkers (CD11c, CD3, FceR1, Ki67, Langerin) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
timeFrame: Baseline (Day 1), Day 15
measure: Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15
timeFrame: Day 15
measure: Number of Participants With Categorical Histological Response at Day 15
timeFrame: Day 15
measure: Number of Participants With Categorical KRT16 Expression at Day 15
timeFrame: Day 15
measure: Change From Baseline in Lesion Severity as Measured by TSS at Day 8
timeFrame: Baseline (Day 1), Day 8
measure: Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15
timeFrame: Baseline (Day 1), Days 8 and 15
measure: Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15
timeFrame: Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups
timeFrame: From first dose of study treatment up to Day 71
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term, Which Occurred in the Treatment Area During the Double-Blind Period
timeFrame: From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Innovaderm Research Incorporated
state: Quebec
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Bissonnette R, Pavel AB, Diaz A, Werth JL, Zang C, Vranic I, Purohit VS, Zielinski MA, Vlahos B, Estrada YD, Saint-Cyr Proulx E, Ports WC, Guttman-Yassky E. Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial. J Allergy Clin Immunol. 2019 Nov;144(5):1274-1289. doi: 10.1016/j.jaci.2019.06.047. Epub 2019 Aug 13.