Crisaborole for Chinese and Japanese Subjects (≥2 Years of Age) With Mild to Moderate Atopic Dermatitis
- Conditions
- Atopic Dermatitis
- Interventions
- Registration Number
- NCT04360187
- Lead Sponsor
- Pfizer
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 391
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Crisaborole ointment Crisaborole Ointment Crisaborole ointment application twice daily for 28 days Crisaborole Placebo Vehicle Crisaborole Placebo Vehicle Vehicle Ointment application twice daily for 28 days
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) 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.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 29 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.
Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters 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.
Percentage of Participants With Clinically Significant Changes From Baseline in Vital Signs 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
Name Time Method Percentage of Participants Achieving EASI-50 Over Time 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.Percentage of Participants Achieving Improvement in Investigator's Static Global Assessment (ISGA) at Day 29 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.
Percentage of Participants Achieving EASI-75 Over Time 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.Change From Baseline in Peak Pruritus NRS Over Time-for Participants ≥12 Years 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.Percentage of Participants Achieving Success in ISGA at Day 29 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.
Change From Baseline in Peak Pruritus Numeric Rating Scale (NRS) at Week 4-for Participants ≥12 Years 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.
Percentage of Participants Achieving Success in ISGA Over Time 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.
Percentage of Participants Achieving Improvement in ISGA Over Time 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) .Percent Change From Baseline in EASI Total Score Over Time 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.
Change From Baseline in Percent Body Surface Area (%BSA) Over Time 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.
Change From Baseline in Patient Reported Itch Severity Scale Over Time-for Participants ≥6 Years and <12 Years 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.
Change From Baseline in Observer Reported Itch Severity Scale Over Time-for Participants <6 Years 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.
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score Over Time 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.
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score Over Time 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.
Change From Infants' Dermatitis Quality of Life Index (IDQOL) Total Score Over Time 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.
Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score Over Time 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.
Change From Baseline in Patient-Oriented Eczema Measure (POEM) Over Time in Participants ≥12 Years 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.
Change From Baseline in POEM Over Time in Participants ≥2 Years and <12 Years 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.
Change From Baseline in Weekly Average of Patient Global Impression of Severity (PGIS) Score 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.Patient Global Impression of Change (PGIC) Score 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'.Change From Baseline in Weekly Average of Observer Reported Global Impression of Severity (OGIS) Score 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.Observer Reported Global Impression of Change (OGIC) Score 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'.
Trial Locations
- Locations (39)
Iryouhoujinshadan Yamayurikai Tsujino. Kodomo Clinic
🇯🇵Kobe-City, Hyōgo, Japan
Miyata Dermatology Clinic
🇯🇵Matsudo City, Chiba, Japan
Chitose dermatology and plastic surgery clinic
🇯🇵Chitose Shi, Hokkaido, Japan
Shirao Clinic of Pediatrics and Pediatric Allergy
🇯🇵Hiroshima-shi, Hiroshima, Japan
Yoshimura Child Clinic
🇯🇵Akashi-City, Hyōgo, Japan
Yoshioka Dermatology Clinic
🇯🇵Neyagawa, Osaka, Japan
Kume Clinic
🇯🇵Sakai-City, Osaka, Japan
Nomura Dermatology Clinic
🇯🇵Yokohama-shi, Kanagawa, Japan
Hallym University Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Sugamo Kobayashi Derma Clinic
🇯🇵Toshima-Ku, Tokyo, Japan
Hoshikuma Dermatology・Allergy Clinic
🇯🇵Fukuoka, Japan
Sugamo Sengoku Dermatology
🇯🇵Toshima-Ku, Tokyo, Japan
Takagi Dermatological Clinic
🇯🇵Obihiro, Hokkaido, Japan
Mildix Skin Clinic
🇯🇵Adachi-ku, Tokyo, Japan
Noguchi Dermatology Clinic
🇯🇵Kamimashiki-gun, Kumamoto, Japan
Yoga Allergy Clinic
🇯🇵Setagaya-ku, Tokyo, Japan
Motomachi Dermatology Clinic
🇯🇵Asahikawa-shi, Hokkaido, Japan
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Dermatology Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Guangzhou First People's Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China
The Second Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Shenzhen Children's Hospital
🇨🇳Shenzhen, Guangdong, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The First hospital of Jilin University
🇨🇳Changchun, Jilin, China
Shandong Provincial Institute of Dermatology and Venereology & Shandong Provincial Hospital for Skin
🇨🇳Jinan, Shandong, China
Huashan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
First Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
Hangzhou Third Hospital
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
The first Affiliated hospital of Wenzhou medical University
🇨🇳Wenzhou, Zhejiang, China
Peking University People's Hospital
🇨🇳Beijing, China
Beijing Children's Hospital, Capital Medical University
🇨🇳Beijing, China
The Second Affiliated Hospital of Army Medical University,PLA
🇨🇳Chongqing, China
Children's Hospital of Shanghai
🇨🇳Shanghai, China
Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital
🇨🇳Tianjin, China
Zhejiang Provincial People's Hospital/Dermatology Department
🇨🇳Hangzhou, Zhejiang, China