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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04360187
• Other study ID #: C3291032
• Status: Completed
• Phase: Phase 3
• Start date: July 27, 2020
• Est. completion date: September 8, 2021

Study information

• Verified date: May 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 391
• Est. completion date: September 8, 2021
• Est. primary completion date: September 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Crisaborole Ointment
Crisaborole ointment 2%
• Crisaborole Placebo Vehicle
Placebo for crisaborole ointment

Locations

Country	Name	City	State
China	Beijing Children's Hospital, Capital Medical University	Beijing
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Peking University People's Hospital	Beijing
China	The First hospital of Jilin University	Changchun	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The Second Affiliated Hospital of Army Medical University,PLA	Chongqing
China	Dermatology Hospital of Southern Medical University	Guangzhou	Guangdong
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Hangzhou Third Hospital	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital/Dermatology Department	Hangzhou	Zhejiang
China	Shandong Provincial Institute of Dermatology and Venereology & Shandong Provincial Hospital for Skin	Jinan	Shandong
China	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Children's Hospital of Shanghai	Shanghai
China	Huashan Hospital Fudan University	Shanghai	Shanghai
China	The First Affiliated Hospital of Shantou University Medical College	Shantou	Guangdong
China	Shenzhen Children's Hospital	Shenzhen	Guangdong
China	Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	The first Affiliated hospital of Wenzhou medical University	Wenzhou	Zhejiang
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
Japan	Mildix Skin Clinic	Adachi-ku	Tokyo
Japan	Yoshimura Child Clinic	Akashi-City	Hyogo
Japan	Motomachi Dermatology Clinic	Asahikawa-shi	Hokkaido
Japan	Chitose dermatology and plastic surgery clinic	Chitose Shi	Hokkaido
Japan	Hoshikuma Dermatology·Allergy Clinic	Fukuoka
Japan	Shirao Clinic of Pediatrics and Pediatric Allergy	Hiroshima-shi	Hiroshima
Japan	Noguchi Dermatology Clinic	Kamimashiki-gun	Kumamoto
Japan	Iryouhoujinshadan Yamayurikai Tsujino. Kodomo Clinic	Kobe-City	Hyogo
Japan	Miyata Dermatology Clinic	Matsudo City	Chiba
Japan	Yoshioka Dermatology Clinic	Neyagawa	Osaka
Japan	Takagi Dermatological Clinic	Obihiro	Hokkaido
Japan	Kume Clinic	Sakai-City	Osaka
Japan	Yoga Allergy Clinic	Setagaya-ku	Tokyo
Japan	Sugamo Kobayashi Derma Clinic	Toshima-Ku	Tokyo
Japan	Sugamo Sengoku Dermatology	Toshima-Ku	Tokyo
Japan	Nomura Dermatology Clinic	Yokohama-shi	Kanagawa
Korea, Republic of	Hallym University Kangnam Sacred Heart Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

China,  Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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