Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crisaborole ointment | Experimental |
| |
| Placebo ointment (vehicle) | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Crisaborole ointment 2% BID | Drug | Crisaborole ointment 2% BID for 15 days (double blind); additional 28 days (open label) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| Change From Baseline in Key Skin Biomarker Interleukin (IL)-13 Expression in Target Lesions Treated With Crisaborole Ointment 2% or Vehicle at Day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Day 1), Day 15 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Innovaderm Research Incorporated | Montreal | Quebec | H2K 4L5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31419544 | Derived | 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. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
Not provided
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Double-Blind Period (Day 1 to Day 15) |
|
| ||||||||||||||||||
| Open-Label Period (Day 15 to Day 71) |
|
All participants who received at least 1 dose of investigational product.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All randomized participants who received at least 1 dose of investigational product and had TSS assessment at Day 15. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Day 15 |
|
From first dose of study treatment up to Day 71
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 Outcome Measure 19 for the treated area AEs).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Crisaborole Ointment 2% + Vehicle in Double-Blind Period | On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the participants who were treated with both crisaborole ointment 2% and vehicle during Days 1 to 14. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Application site pain | General disorders | MedDRA v21.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 2, 2017 | Apr 26, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 1, 2018 | Apr 26, 2019 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| D004485 | Eczema |
| D012871 | Skin Diseases |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
Not provided
Not provided
| ID | Term |
|---|---|
| C494814 | BID protein, human |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo ointment (vehicle) | Drug | Placebo ointment (vehicle) BID for 15 days (double blind) |
|
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. |
| Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| 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. | Baseline (Day 1), Day 15 |
| 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. | Day 15 |
| 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. | Day 15 |
| 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. | Day 15 |
| 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. | Baseline (Day 1), Day 8 |
| 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. | Baseline (Day 1), Days 8 and 15 |
| 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. | Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 |
| 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). | From first dose of study treatment up to Day 71 |
| 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. | From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection |
| To obtain contact information for a study center near you, click here. | View source |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Vehicle Treated Lesion | On Days 1 to 14, for each participant, one target lesion was treated with crisaborole ointment 2% and the other target lesion was treated with vehicle, i.e., each participant was treated with both crisaborole and vehicle. This reporting group represents the other target lesions that were treated with vehicle during Days 1 to 14. |
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2-scale micrometers | Baseline (Day 1), Day 15 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2-scale cells per square millimeter | Baseline (Day 1), Day 15 |
|
|
|
| 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. | 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. | Posted | Mean | Standard Error | log2(normalized expression) | Baseline (Day 1), Day 15 |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Day 15 |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Day 15 |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Day 15 |
|
|
|
| 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. | All randomized participants who received at least 1 dose of investigational product. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Day 8 |
|
|
|
|
| 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. | "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. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Days 8 and 15 |
|
|
|
|
| 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. | "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. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 |
|
|
|
|
| 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). | All participants in each treatment group who received at least 1 dose of investigational product. | Posted | Count of Participants | Participants | From first dose of study treatment up to Day 71 |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | From first dose of study treatment (on Day 1) to Day 15 skin biopsy collection |
|
|
|
| 0 |
| 40 |
| 0 |
| 40 |
| 27 |
| 40 |
| EG001 | Crisaborole Ointment 2% in Open-Label Period | On Days 15 to 42, each participant received crisaborole ointment 2% for all atopic dermatitis skin areas (excluding scalp). | 0 | 39 | 0 | 39 | 16 | 39 |
| Gastroenteritis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
|
| Suture related complication | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Noninfective conjunctivitis | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Application site dermatitis | General disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Application site erythema | General disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Application site paraesthesia | General disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Application site pruritus | General disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Injection site pain | General disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Application site folliculitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
|
| Graft complication | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
|
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Skin plaque | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| FceR1 |
|
| Ki67 |
|
| Langerin |
|
| CCL26 |
|
| CRLF2 |
|
| CXCL1 |
|
| CXCL10 |
|
| CXCL2 |
|
| CXCL9 |
|
| DEFB4A |
|
| FLG |
|
| FOXP3 |
|
| IFNG |
|
| IL-10 |
|
| IL-15 |
|
| IL-15RA |
|
| IL-17A |
|
| IL-17F |
|
| IL-19 |
|
| IL-1B |
|
| IL-2 |
|
| IL-22 |
|
| IL-2RA |
|
| IL-31 |
|
| IL-32 |
|
| IL-5 |
|
| IL-6 |
|
| IL-8 |
|
| IL-9 |
|
| IL-12A |
|
| IL-23A |
|
| LOR |
|
| MMP-12 |
|
| PDE4A |
|
| PDE4B |
|
| PDE4D |
|
| PPL |
|
| RNA18SP5 |
|
| S100A7 |
|
| S100A8 |
|
| S100A9 |
|
| Full normalization |
|
| Worsening |
|
| Good improvement |
|
| Excellent improvement |
|
| Worsening |
|
| Day 15 |
|
|
Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
| Mixed Models Analysis |
| < 0.0001 |
| Least Squares Mean Difference |
| -1.1 |
| Standard Error of the Mean |
| 0.16 |
| 2-Sided |
| 95 |
| -1.4 |
| -0.8 |
Comparison at Day 15 |
| Superiority |
| Day 3 |
|
|
| Day 4 |
|
|
| Day 5 |
|
|
| Day 6 |
|
|
| Day 7 |
|
|
| Day 8 |
|
|
| Day 9 |
|
|
| Day 10 |
|
|
| Day 11 |
|
|
| Day 12 |
|
|
| Day 13 |
|
|
| Day 14 |
|
|
| Day 15 |
|
|
Crisaborole ointment 2% was superior to vehicle if p-value was <0.05.
| Mixed Models Analysis |
| 0.0014 |
| Least-Square Mean of Difference |
| -1.2 |
| Standard Error of the Mean |
| 0.36 |
| 2-Sided |
| 95 |
| -1.9 |
| -0.4 |
Comparison at Day 3 |
| Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | 0.0003 | Least-Square Mean of Difference | -1.3 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.0 | -0.6 | Comparison at Day 4 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.5 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.2 | -0.8 | Comparison at Day 5 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | 0.0003 | Least-Square Mean of Difference | -1.3 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.0 | -0.6 | Comparison at Day 6 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.5 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.3 | -0.8 | Comparison at Day 7 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.8 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.5 | -1.1 | Comparison at Day 8 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.9 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.6 | -1.2 | Comparison at Day 9 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -2.0 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.7 | -1.3 | Comparison at Day 10 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.6 | Standard Error of the Mean | 0.37 | 2-Sided | 95 | -2.3 | -0.9 | Comparison at Day 11 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -2.2 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.9 | -1.5 | Comparison at Day 12 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.9 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.6 | -1.2 | Comparison at Day 13 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.7 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.4 | -1.0 | Comparison at Day 14 | Superiority |
| Crisaborole ointment 2% was superior to vehicle if p-value was <0.05. | Mixed Models Analysis | < 0.0001 | Least-Square Mean of Difference | -1.9 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.7 | -1.2 | Comparison at Day 15 | Superiority |
| Application site pain |
|
| Application site pruritus |
|
| Application site folliculitis |
|
| Post procedural haemorrhage |
|
| Procedural pain |
|
| Suture related complication |
|