Crisaborole for Chinese and Japanese Subjects (≥2 Years of Age) With Mild to Moderate Atopic Dermatitis

A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF CRISABOROLE OINTMENT, 2% IN CHINESE AND JAPANESE PEDIATRIC AND ADULT SUBJECTS (AGES 2 YEARS AND OLDER) WITH MILD TO MODERATE ATOPIC DERMATITIS

This study is a phase 3, randomized, double blind and vehicle study to evaluate the efficacy and safety of Crisaborole ointment, 2% in Chinese and Japanese subjects with mild to moderate atopic dermatitis involving at least 5% treatable BSA. Eligible subjects will be randomized in a 2:1 ratio to one of 2 treatment groups (Crisaborole BID, Vehicle BID, respectively).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Crisaborole Ointment; Drug: Crisaborole Placebo Vehicle

• Study Type: Interventional
• Enrollment (Actual): 391
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100045
    • Beijing Children's Hospital, Capital Medical University
  • Chongqing, China, 400037
    • The Second Affiliated Hospital of Army Medical University,PLA
  • Shanghai, China, 200062
    • Children's Hospital of Shanghai
  • Tianjin, China, 300120
    • Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
    • Guangzhou, Guangdong, China, 510260
      • The Second Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510091
      • Dermatology Hospital of Southern Medical University
    • Shantou, Guangdong, China, 515041
      • The First Affiliated Hospital of Shantou University Medical College
    • Shenzhen, Guangdong, China, 518026
      • Shenzhen Children's Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital Of Central South University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Shandong
    • Jinan, Shandong, China, 250022
      • Shandong Provincial Institute of Dermatology and Venereology & Shandong Provincial Hospital for Skin
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital Fudan University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
    • Hangzhou, Zhejiang, China, 310009
      • Hangzhou Third Hospital
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital/Dermatology Department
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
• Japan
  • Fukuoka, Japan, 814-0171
    • Hoshikuma Dermatology・Allergy Clinic
  • Chiba
    • Matsudo City, Chiba, Japan, 271-0092
      • Miyata Dermatology Clinic
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 734-0023
      • Shirao Clinic of Pediatrics and Pediatric Allergy
  • Hokkaido
    • Asahikawa-shi, Hokkaido, Japan, 070-0810
      • Motomachi Dermatology Clinic
    • Chitose Shi, Hokkaido, Japan, 066-0021
      • Chitose dermatology and plastic surgery clinic
    • Obihiro, Hokkaido, Japan, 080-0013
      • Takagi Dermatological Clinic
  • Hyōgo
    • Akashi-City, Hyōgo, Japan, 674-0068
      • Yoshimura Child Clinic
    • Kobe-City, Hyōgo, Japan, 658-0082
      • Iryouhoujinshadan Yamayurikai Tsujino. Kodomo Clinic
  • Kanagawa
    • Yokohama-shi, Kanagawa, Japan, 221-0825
      • Nomura Dermatology Clinic
  • Kumamoto
    • Kamimashiki-gun, Kumamoto, Japan, 861-3101
      • Noguchi Dermatology Clinic
  • Osaka
    • Neyagawa, Osaka, Japan, 572-0838
      • Yoshioka Dermatology Clinic
    • Sakai-City, Osaka, Japan, 593-8324
      • Kume Clinic
  • Tokyo
    • Adachi-ku, Tokyo, Japan, 120-0034
      • Mildix Skin Clinic
    • Setagaya-ku, Tokyo, Japan, 158-0097
      • Yoga Allergy Clinic
    • Toshima-Ku, Tokyo, Japan, 170-0002
      • Sugamo Kobayashi Derma Clinic
    • Toshima-Ku, Tokyo, Japan, 170-0002
      • Sugamo Sengoku Dermatology
• Korea, Republic of
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years 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) or clinically significant physical examination finding at Screening that in the PI's or designee's opinion may interfere with study objectives.
• Has participated in a previous crisaborole clinical study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crisaborole ointment; Crisaborole ointment application twice daily for 28 days	Drug: Crisaborole Ointment; Crisaborole ointment 2%
Placebo Comparator: Crisaborole Placebo Vehicle; Vehicle Ointment application twice daily for 28 days	Drug: Crisaborole Placebo Vehicle; Placebo for crisaborole ointment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 29	The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of body surface area (BSA) affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.	Baseline, Day 29
Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An adverse event was considered as a treatment-emergent adverse event (TEAE) if the event started after the first dose of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.	Baseline up to Day 60
Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters	Laboratory parameters included: hematology and chemistry. Clinically significant laboratory abnormalities are defined as abnormal values that have clinical manifestations or require medical intervention. Clinically significant laboratory criteria included Hemoglobin <0.8 x lower limit of normal (LLN), Leukocytes >1.5 x upper limit of normal (ULN), Lymphocytes <0.8 x LLN, Lymphocytes/Leukocytes >1.2 x ULN, Neutrophils <0.8 x LLN, Neutrophils >1.2x ULN, Neutrophils/Leukocytes <0.8 x LLN, Basophils/Leukocytes >1.2 x ULN, Eosinophils >1.2 x ULN, Eosinophils/Leukocytes >1.2 x ULN, Monocytes >1.2 x ULN, Monocytes/Leukocytes (%) >1.2 x ULN, Bicarbonate <0.9 x LLN, and Glucose >1.5x ULN.	Baseline up to Day 29
Percentage of Participants With Clinically Significant Changes From Baseline in Vital Signs	Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participants in the seated position, after having sat/lied calmly for at least 5 minutes. Clinically significant vital signs criteria included Diastolic Blood Pressure (DBP) Value <50 mmHg, DBP Change ≥20 mmHg increase, DBP Change ≥20 mmHg decrease, Pulse Rate Value >120 beats per minute (bpm), Systolic Blood Pressure (SBP) Value <90 mmHg, SBP Change ≥30 mmHg increase, SBP Change ≥30mmHg decrease	Baseline up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Improvement in Investigator's Static Global Assessment (ISGA) at Day 29	ISGA assessed the severity of atopic dermatitis (AD) on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Improvement in ISGA is defined as ISGA score of 0 or 1.	Baseline, Day 29
Percentage of Participants Achieving Success in ISGA at Day 29	ISGA assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Success in ISGA is defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline.	Baseline, Day 29
Change From Baseline in Peak Pruritus Numeric Rating Scale (NRS) at Week 4-for Participants ≥12 Years	Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point NRS where 0 is no pruritus and 10 is worst itch imaginable. Change: score at Week 4 minus score at baseline.	Baseline, Week 4
Percentage of Participants Achieving Success in ISGA Over Time	ISGA assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Success in ISGA is defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline.	Baseline, Day 8, Day 15, Day 22, Day 29
Percentage of Participants Achieving Improvement in ISGA Over Time	ISGA (Investigator's Static Global Assessment) assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Improvement in ISGA is defined as an ISGA score of Clear (0) or Almost Clear (1) .	Baseline, Day 8, Day 15, Day 22, Day 29
Percent Change From Baseline in EASI Total Score Over Time	The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of BSA affected. EASI is a composite scoring of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of four body regions, with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.	Baseline, Day 8, Day 15, Day 22, Day 29
Change From Baseline in Percent Body Surface Area (%BSA) Over Time	4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp was excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated.	Baseline, Day 8, Day 15, Day 22, Day 29
Percentage of Participants Achieving EASI-50 Over Time	The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of range from 0.0 to 72.0, with higher scores representing greater severity of atopic dermatitis. EASI-50 is defined as EASI score has ≥50% improvement from baseline.	Baseline, Day 8, Day 15, Day 22, Day 29
Percentage of Participants Achieving EASI-75 Over Time	The EASI quantifies the severity of a participant's AD based on both severity of lesion clinical signs and the percent of BSA affected. The EASI score can vary in increments of range from 0.0 to 72.0, with higher scores representing greater severity of atopic dermatitis. EASI-75 is defined as EASI score has ≥75% improvement from baseline.	Baseline, Day 8, Day 15, Day 22, Day 29
Change From Baseline in Peak Pruritus NRS Over Time-for Participants ≥12 Years	Peak Pruritus NRS is participants-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point NRS where 0 is no pruritus and 10 is worst itch imaginable. Change: score at observation minus score at baseline.	Baseline, Week 1, Week 2, Week 3, Week 4
Change From Baseline in Patient Reported Itch Severity Scale Over Time-for Participants ≥6 Years and <12 Years	Patient Reported Itch Severity Scale is a 5-point scale indicating no itchy to very itchy (ranged from 0 to 4, where 0=no itch to 4=worst itch imaginable) for participants ≥6 and <12 years of age.	Baseline, Week 1, Week 2, Week 3, Week 4
Change From Baseline in Observer Reported Itch Severity Scale Over Time-for Participants <6 Years	Observer Reported Itch Severity Scale is an 11-point (ranged from 0 to 10, where 0=no itch to 10=worst itch imaginable) scale and must be completed by the observer (caregivers of participants) for participants <6 years of age.	Baseline, Week 1, Week 2, Week 3, Week 4
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score Over Time	The DLQI was a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. The questionnaire will be completed by all participants aged 16 years and older, based on the age at Screening Visit/time of informed consent/assent. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.	Baseline, Day 15, Day 29
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score Over Time	The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 4-15 years) quality of life. The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.	Baseline, Day 15, Day 29
Change From Infants' Dermatitis Quality of Life Index (IDQOL) Total Score Over Time	The IDQOL was completed by observer for participants aged 2-3 years, based on the age at the Screening Visit/time of informed consent/assent. The IDQOL is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score the more quality of life is impaired.	Baseline, Day 15, Day 29
Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score Over Time	The DFI was completed by all observer for participants aged 2-17 years, based on the age at Screening Visit/time of informed consent/assent. The minimum DFI score is 0; the maximum DFI score is 30. The higher score means worse outcome.	Baseline, Day 15, Day 29
Change From Baseline in Patient-Oriented Eczema Measure (POEM) Over Time in Participants ≥12 Years	The POEM is a validated 7-item measure used to assess the impact of AD over the past week. The POEM contains 7 symptom based questions with responses rating number of days each symptom is experienced over the past week, from 0 (no days) to 4 (every day), with a maximum score of 28. Higher score means worse outcome.	Baseline, Day 15, Day 29
Change From Baseline in POEM Over Time in Participants ≥2 Years and <12 Years	The POEM is a validated 7-item measure used to assess the impact of AD over the past week. The POEM contains 7 symptom based questions with responses rating number of days each symptom is experienced over the past week, from 0 (no days) to 4 (every day), with a maximum score of 28. Higher score means worse outcome.	Baseline, Day 15, Day 29
Change From Baseline in Weekly Average of Patient Global Impression of Severity (PGIS) Score	The PGIS (for participants 12 years and older) is a single item patient-rated measure of the participant's AD condition severity at a given point in time. This single item instrument uses a 7-point rating scale, which range from 1 to 7, where 1=Not present to 7=Extremely severe.	Baseline, Week 1, Week 2, Week 3, Week 4
Patient Global Impression of Change (PGIC) Score	The PGIC (for participants 12 years and older) was used to determine global improvement as assessed by the participant or caregiver. It was used as an anchor to define a responder definition for the peak pruritus scales for 'clinically important responder' and as a sensitivity analysis for defining a 'clinical important difference' on the peak pruritus scales. This single item instrument is a 7-point rating scale, anchored by (1) 'very much improved' to (7) 'very much worse'.	Day 8, Day 15, Day 22, Day 29
Change From Baseline in Weekly Average of Observer Reported Global Impression of Severity (OGIS) Score	The OGIS (for participants ≥2 and <12 years) is a single item observer-rated measure of the participant's AD condition severity at a given point in time. This single item instrument uses a 7-point rating scale, which ranged from 1 to 7, where 1=Not present to 7=Extremely severe.	Baseline, Week 1, Week 2, Week 3, Week 4
Observer Reported Global Impression of Change (OGIC) Score	The OGIC (for participants ≥2 and <12 years ) was used to determine global improvement as assessed by the participant or caregiver. It was used as an anchor to define a responder definition for the peak pruritus scales for 'clinically important responder' and as a sensitivity analysis for defining a 'clinical important difference' on the peak pruritus scales. This single item instrument is a 7-point rating scale, anchored by (1) 'very much improved' to (7) 'very much worse'.	Day 8, Day 15, Day 22, Day 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): July 27, 2020
• Primary Completion (Actual): September 8, 2021
• Study Completion (Actual): September 8, 2021

Study Registration Dates

• First Submitted: April 4, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): June 7, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• 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
• Other Study ID Numbers: C3291032

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
• product manufactured in and exported from the U.S.: Yes