Phase 2 Completed N=40 Randomized Quadruple-blind Basic Science

Crisaborole Ointment 2% Skin Biomarker Biopsy Study in Atopic Dermatitis

Dermatitis, Atopic

Source: ClinicalTrials.gov NCT03233529 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Aug 2019

Primary outcomePrimary: Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 — -4.5; -2.1 units on a scale — p=<0.0001

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-4.5; -2.1	<0.0001 sig
PRIMARY 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	-1.2787; -0.2881	0.0420 sig
PRIMARY Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-0.7295; -0.1849	0.1519
PRIMARY Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-1.3267; -0.1994	0.0007 sig
PRIMARY Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-0.5484; 0.2128	0.0871
PRIMARY Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-2.4495; -1.0854	0.0055 sig
PRIMARY 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	-2.4235; -1.2989	0.0238 sig
PRIMARY 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	-3.2762; -1.2849	0.0042 sig
SECONDARY Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-0.2737; -0.1779	—
SECONDARY 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	-0.4736; -0.1694; -0.6219; -0.2642; -0.4226; -0.1314	—
SECONDARY Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15	-0.3095; 0.0604; -0.2016; 0.1088; 0.0231; 0.1195	—
SECONDARY Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15	10; 19; 10; 5; 12; 4	—
SECONDARY Number of Participants With Categorical Histological Response at Day 15	18; 30; 21; 9	—
SECONDARY Number of Participants With Categorical KRT16 Expression at Day 15	13; 18; 3; 10; 8; 5	—
SECONDARY Change From Baseline in Lesion Severity as Measured by TSS at Day 8	-3.3; -1.2	< 0.0001 sig
SECONDARY Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15	-1.3; -0.4; -1.9; -0.8	< 0.0001 sig
SECONDARY Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15	-1.9; -1.0; -2.2; -0.9; -2.4; -1.1	0.0188 sig
SECONDARY Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups	27; 16; 0; 0	—
SECONDARY 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	0; 1; 1; 0; 2; 4	—

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03233529). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.