Dermatitis, Atopic
Conditions
Keywords
atopic dermatitis, atopic eczema, eczema, topical treatment, skin diseases, phosphodiesterase-4 inhibitor, PDE-4 inhibitor, crisaborole
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.
Interventions
DRUGCrisaborole ointment 2% BID
Crisaborole ointment 2% BID for 15 days (double blind); additional 28 days (open label)
Placebo ointment (vehicle) BID for 15 days (double blind)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | Baseline (Day 1), Day 15 | The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity. |
| 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 | Baseline (Day 1), Day 15 | CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis. |
| Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | Baseline (Day 1), Day 15 | CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis. |
| Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | Baseline (Day 1), Day 15 | CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis. |
| Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | Baseline (Day 1), Day 15 | IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis. |
| Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | Baseline (Day 1), Day 15 | KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis. |
| 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 | Baseline (Day 1), Day 15 | Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis. |
| 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 | Baseline (Day 1), Day 15 | S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 | The intensity of pruritus was assessed by an NRS, which was a numeric rating scale ranging from 0 (no itching) to 10 (worst imaginable itching), with higher score indicating greater severity. |
| Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | Baseline (Day 1), Day 15 | Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed. |
| 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 | From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection | An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. During double-blind period, there were a total of 2 treatment areas (for target lesions) for each participant. For this outcome measure, treatment-emergent AEs occurred at each treated area during double-blind period were summarized. MedDRA version 21.0 coding dictionary was used. |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups | From first dose of study treatment up to Day 71 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see next Outcome 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 | Baseline (Day 1), Day 15 | CD11c+ dendritic cells (DCs), CD3+ T cells, FcEpsilon + DCs, Ki 67+ cells, and langerin+ cells (for langerhans cells) were studied using IHC. These parameters were referred to as CD11c, CD3, FceR1, Ki67, langerin, respectively, in the outcome measure title above and data table below. Expression data were log2-transformed. |
| Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | Baseline (Day 1), Day 15 | TLDA RT PCR was used to analyze the following other skin biomarkers: CCL13, CCL20, CCL26, CRLF2, CXCL1, CXCL2, CXCL9, CXCL10, DEFB4A, filaggrin (FLG), FOXP3, IFNG, IL-1B, IL-2, IL-2RA, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12A, IL-15, IL-15RA, IL-17A, IL-17F, IL-19, IL-22, IL-23A, IL-31, IL-32, LOR, MMP-12, PDE4A, PDE4B, PDE4D, PPL, RNA18SP5, S100A7, S100A8, and S100A9. Expression levels were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis. |
| Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | Day 15 | FLG expression was studied using IHC and categorized as no change, partial normalization, full normalization, or worsening by a blinded expert pathologist based on visual scoring. |
| Number of Participants With Categorical Histological Response at Day 15 | Day 15 | Histological response was studied using IHC and categorized as non-responder or responder by a blinded expert pathologist based on a global assessment of all thickness, KRT16 and FLG stains. |
| Number of Participants With Categorical KRT16 Expression at Day 15 | Day 15 | KRT16 expression was studied using IHC and categorized as no change, slight improvement, good improvement, excellent improvement, or worsening by a blinded expert pathologist based on visual scoring. |
| Change From Baseline in Lesion Severity as Measured by TSS at Day 8 | Baseline (Day 1), Day 8 | The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity. |
| Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15 | Baseline (Day 1), Days 8 and 15 | The lesion ISGA is an assessment of target lesion severity of atopic dermatitis. The lesion ISGA score ranges from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), with higher score representing greater severity. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2% The study consisted of 2 periods, i.e., a double-blind period from Day 1 to Day 15 skin biopsy collection, and an open-label period from Day 15 skin biopsy collection to the end of study (Day 71). Each participant received double-blind topical administration of crisaborole ointment 2 percent (%) for 1 target lesion and placebo ointment vehicle (referred to as vehicle) for the other target lesion (i.e., each participant was treated with both crisaborole and vehicle), twice daily from Day 1 to Day 14; then received open-label topical administration of crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp) twice daily from Day 15 to Day 42. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Double-Blind Period (Day 1 to Day 15) | Adverse Event | 1 |
| Open-Label Period (Day 15 to Day 71) | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Crisaborole Ointment 2%+Vehicle, Then Crisaborole Ointment 2% |
|---|---|
| Age, Continuous | 32.2 years STANDARD_DEVIATION 11.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 39 |
| other Total, other adverse events | 27 / 40 | 16 / 39 |
| serious Total, serious adverse events | 0 / 40 | 0 / 39 |
Outcome results
Primary
Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
CCL18 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -0.7295 log2(normalized expression) | Standard Error 0.25784 |
| Vehicle Treated Lesion | Change From Baseline in Key Skin Biomarker CCL18 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -0.1849 log2(normalized expression) | Standard Error 0.25272 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.1519Mixed Models Analysis
Primary
Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
CCL22 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -1.3267 log2(normalized expression) | Standard Error 0.24359 |
| Vehicle Treated Lesion | Change From Baseline in Key Skin Biomarker CCL22 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -0.1994 log2(normalized expression) | Standard Error 0.22335 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.0007Mixed Models Analysis
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
CCL17 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by Taqman low density array (TLDA) reverse-transcriptase (RT) polymerase chain reaction (PCR) were normalized to the housekeeping gene ribosomal protein lateral stalk subunit P0 (RPLP0) and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 log2(normalized expression) | Standard Error 0.36339 |
| Vehicle Treated Lesion | 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 | -0.2881 log2(normalized expression) | Standard Error 0.34055 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.042Mixed Models Analysis
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
Elafin/PI3 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 log2(normalized expression) | Standard Error 0.33463 |
| Vehicle Treated Lesion | 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 | -1.2989 log2(normalized expression) | Standard Error 0.35218 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.0238Mixed Models Analysis
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
IL-13 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 log2(normalized expression) | Standard Error 0.25767 |
| Vehicle Treated Lesion | Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | 0.2128 log2(normalized expression) | Standard Error 0.27893 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.0871Mixed Models Analysis
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
KRT16 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 log2(normalized expression) | Standard Error 0.30229 |
| Vehicle Treated Lesion | Change From Baseline in Key Skin Biomarker Keratin 16 (KRT16) Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -1.0854 log2(normalized expression) | Standard Error 0.33131 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.0055Mixed Models Analysis
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
S100A12 is one of the key skin biomarkers of atopic dermatitis. Expression levels tested by TLDA RT PCR were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 log2(normalized expression) | Standard Error 0.39686 |
| Vehicle Treated Lesion | 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 | -1.2849 log2(normalized expression) | Standard Error 0.40613 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.0042Mixed Models Analysis
Primary
Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15
The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product and had TSS assessment at Day 15.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -4.5 units on a scale | Standard Error 0.31 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Total Sign Score (TSS) for Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -2.1 units on a scale | Standard Error 0.35 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-3.1, -1.7]Mixed Models Analysis
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
Epidermal thickness was one of the other skin biomarkers of atopic dermatitis and was studied using immunohistochemistry (IHC). Expression data were log2-transformed.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 log2-scale micrometers | Standard Error 0.10653 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarker (Epidermal Thickness) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | -0.1779 log2-scale micrometers | Standard Error 0.08229 |
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
TLDA RT PCR was used to analyze the following other skin biomarkers: CCL13, CCL20, CCL26, CRLF2, CXCL1, CXCL2, CXCL9, CXCL10, DEFB4A, filaggrin (FLG), FOXP3, IFNG, IL-1B, IL-2, IL-2RA, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12A, IL-15, IL-15RA, IL-17A, IL-17F, IL-19, IL-22, IL-23A, IL-31, IL-32, LOR, MMP-12, PDE4A, PDE4B, PDE4D, PPL, RNA18SP5, S100A7, S100A8, and S100A9. Expression levels were normalized to the housekeeping gene RPLP0 and log2-transformed prior to analysis.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CCL26 | 0.0231 log2(normalized expression) | Standard Error 0.18602 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-22 | -1.4970 log2(normalized expression) | Standard Error 0.39951 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | FOXP3 | -0.5115 log2(normalized expression) | Standard Error 0.12709 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-2RA | -0.8836 log2(normalized expression) | Standard Error 0.19462 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL10 | -1.0779 log2(normalized expression) | Standard Error 0.36531 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-31 | -1.5885 log2(normalized expression) | Standard Error 0.60512 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IFNG | -0.5588 log2(normalized expression) | Standard Error 0.34472 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-32 | -0.2992 log2(normalized expression) | Standard Error 0.16762 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CCL20 | -0.2016 log2(normalized expression) | Standard Error 0.23629 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-5 | -0.3487 log2(normalized expression) | Standard Error 0.51329 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-10 | -0.3773 log2(normalized expression) | Standard Error 0.19458 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-6 | -0.8814 log2(normalized expression) | Standard Error 0.3267 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL2 | -0.5462 log2(normalized expression) | Standard Error 0.21129 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-8 | -1.9805 log2(normalized expression) | Standard Error 0.37922 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-15 | -0.2307 log2(normalized expression) | Standard Error 0.12331 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-9 | -2.2803 log2(normalized expression) | Standard Error 0.71683 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CRLF2 | -0.8058 log2(normalized expression) | Standard Error 0.13728 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-12A | 0.2787 log2(normalized expression) | Standard Error 0.20557 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-15RA | -0.0780 log2(normalized expression) | Standard Error 0.10814 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-23A | -1.2754 log2(normalized expression) | Standard Error 0.26058 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL9 | -0.9941 log2(normalized expression) | Standard Error 0.33692 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | LOR | 0.3759 log2(normalized expression) | Standard Error 0.19707 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-17A | -1.1577 log2(normalized expression) | Standard Error 0.57223 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | MMP-12 | -1.9588 log2(normalized expression) | Standard Error 0.39817 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CCL13 | -0.3095 log2(normalized expression) | Standard Error 0.2152 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PDE4A | 0.0105 log2(normalized expression) | Standard Error 0.12015 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PDE4B | -0.1900 log2(normalized expression) | Standard Error 0.12061 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-17F | -1.9482 log2(normalized expression) | Standard Error 0.79294 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PDE4D | -0.3865 log2(normalized expression) | Standard Error 0.1292 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | DEFB4A | -3.5331 log2(normalized expression) | Standard Error 0.42635 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PPL | -0.3000 log2(normalized expression) | Standard Error 0.09781 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-19 | -3.1946 log2(normalized expression) | Standard Error 0.78012 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | RNA18SP5 | 0.1121 log2(normalized expression) | Standard Error 0.08576 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL1 | -1.4174 log2(normalized expression) | Standard Error 0.23956 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | S100A7 | -2.1764 log2(normalized expression) | Standard Error 0.30729 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-1B | -0.5792 log2(normalized expression) | Standard Error 0.21864 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | S100A8 | -2.4454 log2(normalized expression) | Standard Error 0.36057 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | FLG | -0.2155 log2(normalized expression) | Standard Error 0.18503 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | S100A9 | -2.6155 log2(normalized expression) | Standard Error 0.35209 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-2 | -0.5352 log2(normalized expression) | Standard Error 0.26229 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | S100A9 | -1.2976 log2(normalized expression) | Standard Error 0.33324 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CCL13 | 0.0604 log2(normalized expression) | Standard Error 0.20967 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CCL20 | 0.1088 log2(normalized expression) | Standard Error 0.23212 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CCL26 | 0.1195 log2(normalized expression) | Standard Error 0.2282 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CRLF2 | -0.2023 log2(normalized expression) | Standard Error 0.14431 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL1 | 0.1924 log2(normalized expression) | Standard Error 0.32423 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL10 | 0.6697 log2(normalized expression) | Standard Error 0.37822 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL2 | 0.1945 log2(normalized expression) | Standard Error 0.207 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | CXCL9 | 0.7562 log2(normalized expression) | Standard Error 0.39811 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | DEFB4A | -1.3456 log2(normalized expression) | Standard Error 0.46988 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | FLG | -0.3670 log2(normalized expression) | Standard Error 0.22285 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | FOXP3 | -0.0273 log2(normalized expression) | Standard Error 0.16057 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IFNG | 0.5737 log2(normalized expression) | Standard Error 0.31138 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-10 | 0.2950 log2(normalized expression) | Standard Error 0.17314 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-15 | 0.2193 log2(normalized expression) | Standard Error 0.11761 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-15RA | 0.2110 log2(normalized expression) | Standard Error 0.10624 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-17A | 0.7516 log2(normalized expression) | Standard Error 0.5997 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-17F | 0.5309 log2(normalized expression) | Standard Error 0.88038 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-19 | -0.8108 log2(normalized expression) | Standard Error 0.7546 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-1B | 0.2808 log2(normalized expression) | Standard Error 0.29124 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-2 | 0.2769 log2(normalized expression) | Standard Error 0.16896 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-22 | -0.0170 log2(normalized expression) | Standard Error 0.35503 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-2RA | -0.0824 log2(normalized expression) | Standard Error 0.22176 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-31 | -0.3997 log2(normalized expression) | Standard Error 0.65363 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-32 | 0.1878 log2(normalized expression) | Standard Error 0.15632 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-5 | -0.4148 log2(normalized expression) | Standard Error 0.42311 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-6 | 0.1724 log2(normalized expression) | Standard Error 0.36369 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-8 | -0.1698 log2(normalized expression) | Standard Error 0.42603 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-9 | -1.0530 log2(normalized expression) | Standard Error 0.68305 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-12A | 0.5251 log2(normalized expression) | Standard Error 0.16751 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | IL-23A | -0.1173 log2(normalized expression) | Standard Error 0.28133 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | LOR | -0.1041 log2(normalized expression) | Standard Error 0.21965 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | MMP-12 | -0.4205 log2(normalized expression) | Standard Error 0.34033 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PDE4B | 0.1923 log2(normalized expression) | Standard Error 0.10897 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PDE4D | 0.0736 log2(normalized expression) | Standard Error 0.12231 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PPL | -0.1933 log2(normalized expression) | Standard Error 0.1218 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | RNA18SP5 | -0.0221 log2(normalized expression) | Standard Error 0.0655 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | S100A7 | -0.8782 log2(normalized expression) | Standard Error 0.26498 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | S100A8 | -1.0669 log2(normalized expression) | Standard Error 0.33255 |
| Vehicle Treated Lesion | Change From Baseline in Expression of Other Skin Biomarkers (CCL13, Etc) in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 | PDE4A | 0.1359 log2(normalized expression) | Standard Error 0.11153 |
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
CD11c+ dendritic cells (DCs), CD3+ T cells, FcEpsilon + DCs, Ki 67+ cells, and langerin+ cells (for langerhans cells) were studied using IHC. These parameters were referred to as CD11c, CD3, FceR1, Ki67, langerin, respectively, in the outcome measure title above and data table below. Expression data were log2-transformed.
Time frame: Baseline (Day 1), Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 | CD3 | -0.6219 log2-scale cells per square millimeter | Standard Error 0.15152 |
| Crisaborole Ointment 2% Treated Lesion | 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 | Ki67 | -1.0983 log2-scale cells per square millimeter | Standard Error 0.21512 |
| Crisaborole Ointment 2% Treated Lesion | 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 | FceR1 | -0.4226 log2-scale cells per square millimeter | Standard Error 0.16068 |
| Crisaborole Ointment 2% Treated Lesion | 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 | Langerin | 0.3694 log2-scale cells per square millimeter | Standard Error 0.27896 |
| Crisaborole Ointment 2% Treated Lesion | 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 | CD11c | -0.4736 log2-scale cells per square millimeter | Standard Error 0.18946 |
| Vehicle Treated Lesion | 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 | Langerin | 0.2779 log2-scale cells per square millimeter | Standard Error 0.19645 |
| Vehicle Treated Lesion | 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 | CD11c | -0.1694 log2-scale cells per square millimeter | Standard Error 0.11081 |
| Vehicle Treated Lesion | 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 | CD3 | -0.2642 log2-scale cells per square millimeter | Standard Error 0.13959 |
| Vehicle Treated Lesion | 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 | FceR1 | -0.1314 log2-scale cells per square millimeter | Standard Error 0.16513 |
| Vehicle Treated Lesion | 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 | Ki67 | -0.8971 log2-scale cells per square millimeter | Standard Error 0.19918 |
Secondary
Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15
The lesion ISGA is an assessment of target lesion severity of atopic dermatitis. The lesion ISGA score ranges from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe), with higher score representing greater severity.
Time frame: Baseline (Day 1), Days 8 and 15
Population: Number of Participants Analyzed signifies the number of participants who received at least 1 dose of investigational product. Number Analyzed refers to the number of evaluable participants for specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15 | Day 8 | -1.3 units on a scale | Standard Error 0.16 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15 | Day 15 | -1.9 units on a scale | Standard Error 0.15 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15 | Day 8 | -0.4 units on a scale | Standard Error 0.11 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Investigator Static Global Assessment (ISGA) at Day 8 and Day 15 | Day 15 | -0.8 units on a scale | Standard Error 0.16 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-1.3, -0.6]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-1.4, -0.8]Mixed Models Analysis
Secondary
Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15
The intensity of pruritus was assessed by an NRS, which was a numeric rating scale ranging from 0 (no itching) to 10 (worst imaginable itching), with higher score indicating greater severity.
Time frame: Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
Population: Number of Participants Analyzed signifies the number of participants who received at least 1 dose of investigational product. Number Analyzed refers to the number of evaluable participants for specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 2 | -1.9 units on a scale | Standard Error 0.36 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 3 | -2.2 units on a scale | Standard Error 0.36 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 4 | -2.4 units on a scale | Standard Error 0.33 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 5 | -2.7 units on a scale | Standard Error 0.31 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 6 | -2.6 units on a scale | Standard Error 0.34 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 7 | -3.1 units on a scale | Standard Error 0.36 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 8 | -3.4 units on a scale | Standard Error 0.35 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 9 | -3.4 units on a scale | Standard Error 0.32 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 10 | -3.5 units on a scale | Standard Error 0.34 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 11 | -3.5 units on a scale | Standard Error 0.41 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 12 | -3.7 units on a scale | Standard Error 0.4 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 13 | -4.0 units on a scale | Standard Error 0.38 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 14 | -3.9 units on a scale | Standard Error 0.36 |
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 15 | -3.9 units on a scale | Standard Error 0.38 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 12 | -1.5 units on a scale | Standard Error 0.36 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 2 | -1.0 units on a scale | Standard Error 0.31 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 9 | -1.5 units on a scale | Standard Error 0.34 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 3 | -0.9 units on a scale | Standard Error 0.38 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 14 | -2.2 units on a scale | Standard Error 0.37 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 4 | -1.1 units on a scale | Standard Error 0.33 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 10 | -1.6 units on a scale | Standard Error 0.32 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 5 | -1.1 units on a scale | Standard Error 0.36 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 13 | -2.2 units on a scale | Standard Error 0.39 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 6 | -1.3 units on a scale | Standard Error 0.36 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 11 | -2.0 units on a scale | Standard Error 0.41 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 7 | -1.5 units on a scale | Standard Error 0.35 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 15 | -2.0 units on a scale | Standard Error 0.41 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by Pruritus Numerical Rating Scale (NRS) at Each Visit up to Day 15 | Day 8 | -1.5 units on a scale | Standard Error 0.33 |
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.018895% CI: [-1.6, -0.1]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.001495% CI: [-1.9, -0.4]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.000395% CI: [-2, -0.6]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.2, -0.8]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: 0.000395% CI: [-2, -0.6]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.3, -0.8]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.5, -1.1]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.6, -1.2]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.7, -1.3]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.3, -0.9]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.9, -1.5]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.6, -1.2]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.4, -1]Mixed Models Analysis
Comparison: Crisaborole ointment 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.7, -1.2]Mixed Models Analysis
Secondary
Change From Baseline in Lesion Severity as Measured by TSS at Day 8
The lesion TSS is an assessment of target lesion severity based on the severity of the following 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each of which was rated on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). These 4 ratings were then added to create the TSS, which ranges from 0 (none) to 12 (most severe), with higher score representing greater severity.
Time frame: Baseline (Day 1), Day 8
Population: All randomized participants who received at least 1 dose of investigational product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Change From Baseline in Lesion Severity as Measured by TSS at Day 8 | -3.3 units on a scale | Standard Error 0.36 |
| Vehicle Treated Lesion | Change From Baseline in Lesion Severity as Measured by TSS at Day 8 | -1.2 units on a scale | Standard Error 0.27 |
Comparison: Crisaborole 2% was superior to vehicle if p-value was \<0.05.p-value: <0.000195% CI: [-2.7, -1.4]Mixed Models Analysis
Secondary
Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15
FLG expression was studied using IHC and categorized as no change, partial normalization, full normalization, or worsening by a blinded expert pathologist based on visual scoring.
Time frame: Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | No change | 10 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | Partial normalization | 10 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | Full normalization | 12 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | Worsening | 7 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | Worsening | 11 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | No change | 19 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | Full normalization | 4 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical Filaggrin (FLG) Expression at Day 15 | Partial normalization | 5 Participants |
Secondary
Number of Participants With Categorical Histological Response at Day 15
Histological response was studied using IHC and categorized as non-responder or responder by a blinded expert pathologist based on a global assessment of all thickness, KRT16 and FLG stains.
Time frame: Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical Histological Response at Day 15 | Non-responder | 18 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical Histological Response at Day 15 | Responder | 21 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical Histological Response at Day 15 | Non-responder | 30 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical Histological Response at Day 15 | Responder | 9 Participants |
Secondary
Number of Participants With Categorical KRT16 Expression at Day 15
KRT16 expression was studied using IHC and categorized as no change, slight improvement, good improvement, excellent improvement, or worsening by a blinded expert pathologist based on visual scoring.
Time frame: Day 15
Population: All randomized participants who received at least 1 dose of investigational product, with both Day 1 and Day 15 biopsies done, and without protocol violations that were thought to impact the biomarker expression during the double-blind vehicle-controlled period.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Good improvement | 8 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Slight improvement | 3 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Excellent improvement | 12 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Worsening | 3 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | No change | 13 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Worsening | 5 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | No change | 18 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Slight improvement | 10 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Good improvement | 5 Participants |
| Vehicle Treated Lesion | Number of Participants With Categorical KRT16 Expression at Day 15 | Excellent improvement | 1 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups
AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. Each participant received both crisaborole (for one target lesion) and vehicle (for the other target lesion) on the same days during double-blind period, and only crisaborole during open-label period; therefore AEs were reported for each treatment group for participants to capture all AEs, instead of each treatment for treated area as it only captures AEs occurred at treated areas (see next Outcome Measure).
Time frame: From first dose of study treatment up to Day 71
Population: All participants in each treatment group who received at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups | Treatment-emergent AEs | 27 Participants |
| Crisaborole Ointment 2% Treated Lesion | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups | Treatment-emergent SAEs | 0 Participants |
| Vehicle Treated Lesion | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups | Treatment-emergent AEs | 16 Participants |
| Vehicle Treated Lesion | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) by Treatment Groups | Treatment-emergent SAEs | 0 Participants |
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
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of study treatment. During double-blind period, there were a total of 2 treatment areas (for target lesions) for each participant. For this outcome measure, treatment-emergent AEs occurred at each treated area during double-blind period were summarized. MedDRA version 21.0 coding dictionary was used.
Time frame: From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection
Population: This outcome measure was summarized by the treatment areas during the double-blind period; therefore, the analysis population here represents the participants who received at least 1 dose of investigational product for each treatment area in double-blind period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crisaborole Ointment 2% Treated Lesion | 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 | Application site dermatitis | 0 Participants |
| Crisaborole Ointment 2% Treated Lesion | 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 | Application site erythema | 1 Participants |
| Crisaborole Ointment 2% Treated Lesion | 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 | Application site pain | 2 Participants |
| Crisaborole Ointment 2% Treated Lesion | 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 | Application site pruritus | 1 Participants |
| Crisaborole Ointment 2% Treated Lesion | 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 | Application site folliculitis | 1 Participants |
| Crisaborole Ointment 2% Treated Lesion | 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 | Post procedural haemorrhage | 0 Participants |
| Crisaborole Ointment 2% Treated Lesion | 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 | Procedural pain | 2 Participants |
| Crisaborole Ointment 2% Treated Lesion | 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 | Suture related complication | 1 Participants |
| Vehicle Treated Lesion | 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 | Suture related complication | 2 Participants |
| Vehicle Treated Lesion | 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 | Application site dermatitis | 1 Participants |
| Vehicle Treated Lesion | 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 | Application site folliculitis | 0 Participants |
| Vehicle Treated Lesion | 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 | Application site erythema | 0 Participants |
| Vehicle Treated Lesion | 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 | Procedural pain | 2 Participants |
| Vehicle Treated Lesion | 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 | Application site pain | 4 Participants |
| Vehicle Treated Lesion | 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 | Post procedural haemorrhage | 1 Participants |
| Vehicle Treated Lesion | 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 | Application site pruritus | 2 Participants |