A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD

A PHASE 3B/4, MULTICENTER, RANDOMIZED, ASSESSOR BLINDED, VEHICLE AND ACTIVE (TOPICAL CORTICOSTEROID AND CALCINEURIN INHIBITOR) CONTROLLED, PARALLEL GROUP STUDY OF THE EFFICACY, SAFETY, AND LOCAL TOLERABILITY OF CRISABOROLE OINTMENT, 2% IN PEDIATRIC AND ADULT SUBJECTS (AGES 2 YEARS AND OLDER) WITH MILD TO MODERATE ATOPIC DERMATITIS

This 4-week study will evaluate the safety and efficacy of crisaborole ointment 2%; crisaborole vehicle; topical corticosteroid and topical calcineurin inhibitor, applied twice daily (BID) in subjects who are at least 2 years of age with mild-moderate AD.

A Sub-Study of Optical Coherence Tomography and Biomarkers in Subjects ages 2 to <18 years old, with Mild to Moderate Atopic Dermatitis, treated with Crisaborole Ointment, 2% or Crisaborole Vehicle Ointment or Hydrocortisone Butyrate 0.1% Cream applied BID will also be conducted at select sites.

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Crisaborole ointment, 2%; Drug: Hydrocortisone butyrate cream, 0.1%; Drug: Pimecrolimus cream, 1%; Drug: Crisaborole Vehicle

Detailed Description

Approximately 600 subjects will be enrolled in the study, of which at least 150 subjects aged 2-6; at least 140 subjects aged 7-11; at least 120 subjects aged 12-17 and up to 90 subjects will be adults. Subjects must have mild-moderate AD involving at least 5% treatable %BSA assessed on baseline/Day 1. Treatable %BSA will be defined as the percent of a subject's total body surface area that is AD involved, excluding the scalp.

Eligible subjects will be randomized at the Baseline/Day 1 visit. Randomization will be stratified by eligibility for TCS or TCI treatment as per national approved labels. Cohort 1 will be for subjects who are eligible for TCS therapy, and Cohort 2 will be for subjects who are not eligible for TCS therapy but eligible for TCI therapy. The investigational products will be applied BID for 28 days to the Treatable body surface area (BSA) identified at Baseline/Day 1.

The primary efficacy endpoint is the percent change from baseline in the Eczema Area and Severity Index (EASI) total score at Day 29.

For the efficacy comparison of crisaborole versus vehicle, subjects from both Cohort 1 and Cohort 2 are included in the analysis, adjusted for cohort effect. For the efficacy comparison of crisaborole versus TCS, only subjects from Cohort 1 are included in the analysis. For the comparison of crisaborole versus TCI, only subjects from Cohort 2 are included in the analysis.

Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment.

Scheduled study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8, Day 15, Day 22, Day 29 (End of treatment/Early termination), Day 43 or 14 Days after last dose if subject is terminated early from treatment. A follow up telephone call will be made by site staff to the subjects/subject's legally acceptable guardian(s) on Day 60 or at least 28 days after last dose if subject is terminated early from treatment. The Day 60 visit will be completed in the clinic for subjects enrolled in the OCT sub-study.

To further explore the benefit/risk of crisaborole ointment, 2%, a sub-study to evaluate differences in atrophic skin changes across study treatment groups in Cohort 1 will be conducted at select sites.

The sub-study will include obtaining Optical coherence tomography (OCT) imaging to evaluate atrophic changes in epidermal thickness during and after treatment with study investigational product in Cohort 1. This sub-study also provides an opportunity to explore differences in Transepidermal Water Loss (TEWL) and cutaneous inflammatory and barrier biomarkers associated with AD within the stratum corneum (SC) across treatment groups in Cohort 1. The Aquaflux (an evaporimeter) will be used in this sub-study to evaluate TEWL during and after treatment at select sub-study centers. Tape-strips will also be used in this sub-study to evaluate SC biomarkers from AD lesional and non-lesional skin.

This sub-study will include approximately 60 subjects from Cohort 1 that are enrolled in the main study (C3291037). Subjects will follow the main study assessments and visits as per the schedule of activities for the main study but will also follow additional procedures as described in the protocol. The telephone call at Day 60 in the main study is replaced with an in-clinic visit for sub-study participants.

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10789
    • ISA - Interdisciplinary Study Association GmbH
  • Frankfurt am Main, Germany, 60590
    • Universitaetsklinikum Frankfurt
  • Bayern
    • Munchen, Bayern, Germany, 80337
      • Klinikum der Universität München
  • NRW
    • Bonn, NRW, Germany, 53127
      • Universitatsklinikum Bonn
  • Niedersachsen
    • Bad Bentheim, Niedersachsen, Germany, 48455
      • Fachklinik Bad Bentheim, Fachbereich Dermatologie und Allergologie, Dermatologische Ambulanz
  • Schleswig-holstein
    • Lubeck, Schleswig-holstein, Germany, 23538
      • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
• Italy
  • AQ
    • L'Aquila, AQ, Italy, 67100
      • UOSD Dermatologia Gen. ed Oncologica DU, PO San Salvatore
  • GE
    • Genova, GE, Italy, 16132
      • DiSSal Sezione di Dermatologia Az. Ospedaliera Universitaria
  • RM
    • Roma, RM, Italy, 00189
      • Ospedale San Pietro Fatebenefratelli
  • Rome
    • Roma, Rome, Italy, 00133
      • Azienda Ospedaliero - Universitaria Policlinico Tor Vergata
• Poland
  • Katowice, Poland, 40-282
    • Silmedic sp. z o.o
  • Krakow, Poland, 31-501
    • Krakowskie Centrum Medyczne Sp. z o.o.
  • Warszawa, Poland, 02-962
    • Royalderm Agnieszka Nawrocka
  • Warszawa, Poland, 02-953
    • Klinika Ambroziak Sp. z O. O.
  • Malopolska
    • Krakow, Malopolska, Poland, 31559
      • Barbara Rewerska Diamond Clinic
• Sweden
  • Orebro, Sweden, 701 85
    • Barn och Ungdomskliniken
  • Orebro, Sweden, 703 62
    • Avdelningen för kliniska prövningar
• Switzerland
  • Bern, Switzerland, 3010
    • Universitatsklinik fuer Dermatologie
  • Lausanne, Switzerland, 1004
    • Centre Hospitalier Universitaire Vaudois (CHUV)
  • Zurich, Switzerland, 8032
    • Universitäts-Kinderspital Zürich
• United Kingdom
  • Cornwall
    • Torpoint, Cornwall, United Kingdom, PL11 2TB
      • Rame Medical Ltd, Penntorr Health
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • NHS Tayside, Ninewells Hospital and Medical School
• United States
  • Arkansas
    • Bryant, Arkansas, United States, 72022
      • Dermatology Trial Associates
  • California
    • Encinitas, California, United States, 92024
      • California Dermatology & Clinical Research Institute
  • Florida
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology
    • Sweetwater, Florida, United States, 33172
      • Lenus Research & Medical Group, LLC
    • Tampa, Florida, United States, 33613
      • Forcare Clinical Research
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • DS Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3-Wake Research, Inc.
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center, Inc.
  • Utah
    • Layton, Utah, United States, 84041
      • Tanner Clinic
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Is male or female 2 years and older at the Screening visit/time of informed consent/assent diagnosed with mild-moderate AD (according to the criteria of Hanifin and Rajka), of at least 5% BSA.

Exclusion Criteria:

Has any clinically significant medical disorder, condition, or disease (including active or potentially recurrent non AD dermatological conditions and known genetic dermatological conditions that overlap with AD, such as Netherton syndrome.

Subjects in Cohort 1 are excluded if they have a contraindication for treatment with hydrocortisone butyrate cream 0.1%

Subjects in Cohort 2 are excluded if they have a contraindication for treatment with pimecrolimus cream, 1%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crisaborole ointment, 2%; This treatment arm will be administered both in Cohort 1 and Cohort 2.	Drug: Crisaborole ointment, 2%; Applied twice a day (BID); Other Names: Eucrisa
Active Comparator: Hydrocortisone butyrate cream, 0.1%; This treatment arm will be administered in Cohort 1 only.	Drug: Hydrocortisone butyrate cream, 0.1%; Applied BID; Other Names: Locoid 0.1%
Active Comparator: Pimecrolimus cream, 1%; This treatment arm will be administered in Cohort 2 only.	Drug: Pimecrolimus cream, 1%; Applied BID; Other Names: Elidel
Placebo Comparator: Crisaborole Vehicle; This treatment arm will be administered both in Cohort 1 and Cohort 2.	Drug: Crisaborole Vehicle; Applied BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in the Eczema Area and Severity Index (EASI) Total Score at Day 29	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and percent (%) body surface area (%BSA) affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score (A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.	Baseline, Day 29
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Discontinuations Due to AEs and SAEs	An AE is any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs are events between the first dose of study drug up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A SAE is any untoward medical occurrence at any dose that: results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event.	From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)
Number of Participants With Local Tolerability Adverse Events (AEs)	Local tolerability AEs included application and instillation site reactions, application site discharge, application site erythema, application site exfoliation, application site pain, application site pruritus, application site swelling, dermatitis and eczema, dermatitis atopic, dermatitis contact, eczema, skin irritation, telangiectasia and related conditions, and urticarias.	From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)
Number of Participants With Clinically Significant Changes in Vital Signs	Vital sign measurements included temperature, respiratory rate, pulse rate, and blood pressure. Temperature, respiratory rate, pulse rate, and blood pressure were taken in the seated or supine position, after the participant has been sitting or lying calmly for a minimum of 5 minutes (when possible for younger children). Position of recording was consistent within participant through-out the study.	Screening up to Day 29
Number of Participants With Clinically Significant Abnormal Laboratory Parameters	Hematology parameters included with criteria greater than (>) 1.2*upper limit of normal (ULN): leukocytes (10^3 per cubic millimeter [10^3/mm^3]), lymphocytes (10^3/mm^3), lymphocytes/leukocytes (%), neutrophils (10^3/mm^3), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils (10^3/mm^3), eosinophils/leukocytes (%), monocytes (10^3/mm^3), monocytes/leukocytes (%). Clinical chemistry included parameters: aspartate aminotransferase (units per liter [U/L]) (>3.0* ULN), alanine aminotransferase (U/L) (>3.0* ULN), alkaline phosphatase (U/L) (>3.0* ULN), creatinine (milligram per deciliter [mg/dL]) (>1.3* ULN), potassium (milliequivalent per liter [mEq/L]) (>1.1* ULN), bicarbonate (mEq/L) (>1.1* ULN).	Screening up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15 and 22	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.	Baseline, Day 8, 15 and 22
Number of Participants Who Achieved Success in the Investigator's Static Global Assessment (ISGA) (ISGA Score of Clear [0] or Almost Clear [1] With At-least a 2-Grade Improvement From Baseline) at Day 8, 15, 22 and 29	ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0= clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.	Day 8, 15, 22 and 29
Number of Participants Who Achieved Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 8, 15, 22 and 29	ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.	Day 8, 15, 22 and 29
Number of Participants Who Achieved Greater Than or Equal to (>=) 75 Percent (%) Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15, 22 and 29	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.	Day 8, 15, 22 and 29
Time to First Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score of Greater Than or Equal to (>=) 75%	EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck [h], upper limbs [u], trunk [t] [including axillae, groin], lower limbs [l] [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%), 6 (90 to 100%). Total EASI score (aged >=8 years) =0.1*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et + It +Ext + Lt) + 0.4*Al*(El + Il + Exl + Ll); for aged 2 to <8 years =0.2*Ah*(Eh + Ih + Exh + Lh) + 0.2*Au*(Eu + Iu + Exu + Lu) + 0.3*At*(Et +It + Ext + Lt) + 0.3*Al*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.	Baseline up to Day 43
Change From Baseline in Percent Body Surface Area (%BSA) at Day 8, 15, 22 and 29	Four body regions were evaluated: head and neck, upper limbs, trunk (including axillae) and lower limbs (including buttocks) excluding scalp. BSA was calculated using handprint method. Number of handprints (size of participant's full palmer hand in a closed position) fitting in affected area of a body region was estimated. Maximum number of handprints were: 10 for head, neck (20 for <8 years age), 20 for upper limbs, 30 for trunk, 40 for lower limbs (30 for <8 years age). Surface area (SA) of body region equivalent to 1 handprint: 10% for head, neck (5% for <8 years age), 5% for upper limbs, 3.33% for trunk, 2.5% for lower limbs (3.33% for <8 years age). Overall %BSA for a body region = total number of handprints in a body region * % SA equivalent to 1 handprint. % BSA for an individual: mean of % BSA of all 4 body regions, range =0-100%, higher values = greater AD severity.	Baseline, Day 8, 15, 22 and 29
Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29	The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged >=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Baseline, Day 8, 15, 22 and 29
Change From Baseline in Participant Reported Itch Severity Scale in Participants Aged 6-11 Years at Day 8, 15, 22 and 29	The severity of itch (pruritus) due to AD was assessed using the five-category participant reported itch severity scale for participants aged 6-11 years. Participants at specified time points were asked to "circle the face that shows how itchy your skin has been today". The scale ranged from 0 to 4, where 0= no itch and 4= very itch. Higher scores indicated worse itch.	Baseline, Day 8, 15, 22 and 29
Change From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29	The severity of itch (pruritus) due to AD was assessed using the participant reported itch severity scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Baseline, Day 8, 15, 22 and 29
Time to Greater Than or Equal to (>=2) Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>) 12 Years	The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged >12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Baseline up to Day 29
Time to >= 3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>)12 Years	The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged >12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Baseline up to Day 29
Time >=2 Point to Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years	The severity of itch (pruritus) due to AD was assessed using the patient reported itch severity scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Baseline up to Day 29
Time to >=3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years	The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Baseline up to Day 29
Number of Participants Who Achieved >=2 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29	The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged >=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Day 8, 15, 22 and 29
Number of Participants Who Achieved >=3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29	The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged >=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Day 8, 15, 22 and 29
Number of Participants Who Achieved Greater Than or Equal to (>=) 2 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29	The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Day 8, 15, 22 and 29
Number of Participants Who Achieved Greater Than or Equal to (>=) 3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29	The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged <6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.	Day 8, 15, 22 and 29
Change From Baseline in Dermatology Life Quality Index (DLQI) in Participants Greater Than or Equal to (>=) 16 Years at Day 8, 15, 22 and 29	DLQI is a 10-item questionnaire that measures the impact of skin disease on participants aged >=16 years. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participant.	Baseline, Day 8, 15, 22 and 29
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) in Participants Aged 4-15 Years at Day 8, 15, 22 and 29	The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 4 to 15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranged from 0 (not at all) to 30 (very much): 0-1 = no effect on the child's life; 2-6 = small effect; 7-12 = moderate effect; 13-18 = very large effect; 19-30 = extremely large effect. Higher scores indicated more impact on quality of life of children.	Baseline, Day 8, 15, 22 and 29
Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) in Participants Aged 2-17 Years at Day 8, 15, 22 and 29	The DFI was a 10-item disease questionnaire that measures the impact of having a child (aged 2-17 years) with AD on family quality of life. It was completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question was scored on a 4-point scale ranging from 0 (not at all) to 30 (very much): where higher scores indicated worst quality of life of family. The DFI total score was the sum of individual scores of the 10 questions and ranged from 0 (no impact on life of family) to 30 (maximum effect on life of family), where higher DFI scores indicated maximum effect on life of family.	Baseline, Day 8, 15, 22 and 29

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2018
• Primary Completion (Actual): December 11, 2020
• Study Completion (Actual): December 11, 2020

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): January 10, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Atopic Dermatitis, Crisaborole ointment 2%, TCS, TCI
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Calcineurin Inhibitors; Hydrocortisone; Pimecrolimus; Hydrocortisone-17-butyrate
• Other Study ID Numbers: C3291037; 2018-001043-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No