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

• ClinicalTrials.gov Identifier: NCT04360187
• Recruitment Status: Completed
• First Posted: April 24, 2020
• Results First Posted: May 2, 2022
• Last Update Posted: June 7, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Atopic Dermatitis	Drug: Crisaborole Ointment; Drug: Crisaborole Placebo Vehicle	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 391 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 27, 2020
• Actual Primary Completion Date: September 8, 2021
• Actual Study Completion Date: September 8, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 29 [ Time Frame: Baseline, 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.
2. Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 60 ]
   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.
3. Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters [ Time Frame: Baseline up to Day 29 ]
   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.
4. Percentage of Participants With Clinically Significant Changes From Baseline in Vital Signs [ Time Frame: Baseline up to Day 29 ]
   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

Secondary Outcome Measures :

1. Percentage of Participants Achieving Improvement in Investigator's Static Global Assessment (ISGA) at Day 29 [ Time Frame: Baseline, 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.
2. Percentage of Participants Achieving Success in ISGA at Day 29 [ Time Frame: Baseline, 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.
3. Change From Baseline in Peak Pruritus Numeric Rating Scale (NRS) at Week 4-for Participants ≥12 Years [ Time Frame: Baseline, Week 4 ]
   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.
4. Percentage of Participants Achieving Success in ISGA Over Time [ Time Frame: Baseline, Day 8, Day 15, Day 22, 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.
5. Percentage of Participants Achieving Improvement in ISGA Over Time [ Time Frame: Baseline, Day 8, Day 15, Day 22, Day 29 ]

   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) .

6. Percent Change From Baseline in EASI Total Score Over Time [ Time Frame: Baseline, Day 8, Day 15, Day 22, Day 29 ]
   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.
7. Change From Baseline in Percent Body Surface Area (%BSA) Over Time [ Time Frame: Baseline, Day 8, Day 15, Day 22, Day 29 ]
   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.
8. Percentage of Participants Achieving EASI-50 Over Time [ Time Frame: Baseline, Day 8, Day 15, Day 22, Day 29 ]

   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.

9. Percentage of Participants Achieving EASI-75 Over Time [ Time Frame: Baseline, Day 8, Day 15, Day 22, Day 29 ]

   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.

10. Change From Baseline in Peak Pruritus NRS Over Time-for Participants ≥12 Years [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4 ]

    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.

11. Change From Baseline in Patient Reported Itch Severity Scale Over Time-for Participants ≥6 Years and <12 Years [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4 ]
    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.
12. Change From Baseline in Observer Reported Itch Severity Scale Over Time-for Participants <6 Years [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4 ]
    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.
13. Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score Over Time [ Time Frame: Baseline, Day 15, Day 29 ]
    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.
14. Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score Over Time [ Time Frame: Baseline, Day 15, Day 29 ]
    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.
15. Change From Infants' Dermatitis Quality of Life Index (IDQOL) Total Score Over Time [ Time Frame: Baseline, Day 15, Day 29 ]
    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.
16. Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score Over Time [ Time Frame: Baseline, Day 15, Day 29 ]
    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.
17. Change From Baseline in Patient-Oriented Eczema Measure (POEM) Over Time in Participants ≥12 Years [ Time Frame: Baseline, Day 15, Day 29 ]
    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.
18. Change From Baseline in POEM Over Time in Participants ≥2 Years and <12 Years [ Time Frame: Baseline, Day 15, Day 29 ]
    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.
19. Change From Baseline in Weekly Average of Patient Global Impression of Severity (PGIS) Score [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4 ]

    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.

20. Patient Global Impression of Change (PGIC) Score [ Time Frame: Day 8, Day 15, Day 22, Day 29 ]

    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'.

21. Change From Baseline in Weekly Average of Observer Reported Global Impression of Severity (OGIS) Score [ Time Frame: Baseline, Week 1, Week 2, Week 3, Week 4 ]

    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.

22. Observer Reported Global Impression of Change (OGIC) Score [ Time Frame: Day 8, Day 15, Day 22, Day 29 ]

    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'.

Eligibility Criteria

• Ages Eligible for Study: 2 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China, Beijing

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing, China, 100050

China, Guangdong

Dermatology Hospital of Southern Medical University

Guangzhou, Guangdong, China, 510091

Guangzhou First People's Hospital

Guangzhou, Guangdong, China, 510180

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China, 510260

The First Affiliated Hospital of Shantou University Medical College

Shantou, Guangdong, China, 515041

Shenzhen Children's Hospital

Shenzhen, Guangdong, China, 518026

China, Hubei

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China, 430030

China, Hunan

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China, 410011

China, Jilin

The First hospital of Jilin University

Changchun, Jilin, China, 130021

China, Shandong

Shandong Provincial Institute of Dermatology and Venereology & Shandong Provincial Hospital for Skin

Jinan, Shandong, China, 250022

China, Shanghai

Huashan Hospital Fudan University

Shanghai, Shanghai, China, 200040

China, Tianjin

Tianjin Medical University General Hospital

Tianjin, Tianjin, China, 300052

China, Yunnan

First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China, 650032

China, Zhejiang

Hangzhou Third Hospital

Hangzhou, Zhejiang, China, 310009

Zhejiang Provincial People's Hospital/Dermatology Department

Hangzhou, Zhejiang, China, 310014

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310016

The first Affiliated hospital of Wenzhou medical University

Wenzhou, Zhejiang, China, 325000

China

Peking University People's Hospital

Beijing, China, 100044

Beijing Children's Hospital, Capital Medical University

Beijing, China, 100045

The Second Affiliated Hospital of Army Medical University,PLA

Chongqing, China, 400037

Children's Hospital of Shanghai

Shanghai, China, 200062

Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital

Tianjin, China, 300120

Japan

Miyata Dermatology Clinic

Matsudo City, Chiba, Japan, 271-0092

Shirao Clinic of Pediatrics and Pediatric Allergy

Hiroshima-shi, Hiroshima, Japan, 734-0023

Motomachi Dermatology Clinic

Asahikawa-shi, Hokkaido, Japan, 070-0810

Chitose dermatology and plastic surgery clinic

Chitose Shi, Hokkaido, Japan, 066-0021

Takagi Dermatological Clinic

Obihiro, Hokkaido, Japan, 080-0013

Yoshimura Child Clinic

Akashi-City, Hyōgo, Japan, 674-0068

Iryouhoujinshadan Yamayurikai Tsujino. Kodomo Clinic

Kobe-City, Hyōgo, Japan, 658-0082

Nomura Dermatology Clinic

Yokohama-shi, Kanagawa, Japan, 221-0825

Noguchi Dermatology Clinic

Kamimashiki-gun, Kumamoto, Japan, 861-3101

Yoshioka Dermatology Clinic

Neyagawa, Osaka, Japan, 572-0838

Kume Clinic

Sakai-City, Osaka, Japan, 593-8324

Mildix Skin Clinic

Adachi-ku, Tokyo, Japan, 120-0034

Yoga Allergy Clinic

Setagaya-ku, Tokyo, Japan, 158-0097

Sugamo Kobayashi Derma Clinic

Toshima-Ku, Tokyo, Japan, 170-0002

Sugamo Sengoku Dermatology

Toshima-Ku, Tokyo, Japan, 170-0002

Hoshikuma Dermatology・Allergy Clinic

Fukuoka, Japan, 814-0171

Korea, Republic of

Hallym University Kangnam Sacred Heart Hospital

Seoul, Korea, Republic of, 07441

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] December 18, 2020

Statistical Analysis Plan  [PDF] September 18, 2021

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04360187
• Other Study ID Numbers: C3291032
• First Posted: April 24, 2020
• Results First Posted: May 2, 2022
• Last Update Posted: June 7, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• 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

Additional relevant MeSH terms:

Dermatitis, Atopic; Dermatitis; Eczema; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases