Crisaborole for Chinese and Japanese Subjects (≥2 Years of Age) With Mild to Moderate Atopic Dermatitis
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT04360187
Collaborator
(none)
391
39
2
13.4
10
0.7
Study Details
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 |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
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
:
Jul 27, 2020
Actual Primary Completion Date
:
Sep 8, 2021
Actual Study Completion Date
:
Sep 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
- 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 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.
- 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
- 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 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.
- 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 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.
- 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'.
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Friendship Hospital, Capital Medical University | Beijing | Beijing | China | 100050 |
| 2 | Dermatology Hospital of Southern Medical University | Guangzhou | Guangdong | China | 510091 |
| 3 | Guangzhou First People's Hospital | Guangzhou | Guangdong | China | 510180 |
| 4 | The Second Affiliated Hospital of Guangzhou Medical University | Guangzhou | Guangdong | China | 510260 |
| 5 | The First Affiliated Hospital of Shantou University Medical College | Shantou | Guangdong | China | 515041 |
| 6 | Shenzhen Children's Hospital | Shenzhen | Guangdong | China | 518026 |
| 7 | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | Hubei | China | 430030 |
| 8 | The Second Xiangya Hospital of Central South University | Changsha | Hunan | China | 410011 |
| 9 | The First hospital of Jilin University | Changchun | Jilin | China | 130021 |
| 10 | Shandong Provincial Institute of Dermatology and Venereology & Shandong Provincial Hospital for Skin | Jinan | Shandong | China | 250022 |
| 11 | Huashan Hospital Fudan University | Shanghai | Shanghai | China | 200040 |
| 12 | Tianjin Medical University General Hospital | Tianjin | Tianjin | China | 300052 |
| 13 | First Affiliated Hospital of Kunming Medical University | Kunming | Yunnan | China | 650032 |
| 14 | Hangzhou Third Hospital | Hangzhou | Zhejiang | China | 310009 |
| 15 | Zhejiang Provincial People's Hospital/Dermatology Department | Hangzhou | Zhejiang | China | 310014 |
| 16 | Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University | Hangzhou | Zhejiang | China | 310016 |
| 17 | The first Affiliated hospital of Wenzhou medical University | Wenzhou | Zhejiang | China | 325000 |
| 18 | Peking University People's Hospital | Beijing | China | 100044 | |
| 19 | Beijing Children's Hospital, Capital Medical University | Beijing | China | 100045 | |
| 20 | The Second Affiliated Hospital of Army Medical University,PLA | Chongqing | China | 400037 | |
| 21 | Children's Hospital of Shanghai | Shanghai | China | 200062 | |
| 22 | Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital | Tianjin | China | 300120 | |
| 23 | Miyata Dermatology Clinic | Matsudo City | Chiba | Japan | 271-0092 |
| 24 | Shirao Clinic of Pediatrics and Pediatric Allergy | Hiroshima-shi | Hiroshima | Japan | 734-0023 |
| 25 | Motomachi Dermatology Clinic | Asahikawa-shi | Hokkaido | Japan | 070-0810 |
| 26 | Chitose dermatology and plastic surgery clinic | Chitose Shi | Hokkaido | Japan | 066-0021 |
| 27 | Takagi Dermatological Clinic | Obihiro | Hokkaido | Japan | 080-0013 |
| 28 | Yoshimura Child Clinic | Akashi-City | Hyōgo | Japan | 674-0068 |
| 29 | Iryouhoujinshadan Yamayurikai Tsujino. Kodomo Clinic | Kobe-City | Hyōgo | Japan | 658-0082 |
| 30 | Nomura Dermatology Clinic | Yokohama-shi | Kanagawa | Japan | 221-0825 |
| 31 | Noguchi Dermatology Clinic | Kamimashiki-gun | Kumamoto | Japan | 861-3101 |
| 32 | Yoshioka Dermatology Clinic | Neyagawa | Osaka | Japan | 572-0838 |
| 33 | Kume Clinic | Sakai-City | Osaka | Japan | 593-8324 |
| 34 | Mildix Skin Clinic | Adachi-ku | Tokyo | Japan | 120-0034 |
| 35 | Yoga Allergy Clinic | Setagaya-ku | Tokyo | Japan | 158-0097 |
| 36 | Sugamo Kobayashi Derma Clinic | Toshima-Ku | Tokyo | Japan | 170-0002 |
| 37 | Sugamo Sengoku Dermatology | Toshima-Ku | Tokyo | Japan | 170-0002 |
| 38 | Hoshikuma Dermatology・Allergy Clinic | Fukuoka | Japan | 814-0171 | |
| 39 | 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)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT04360187
Other Study ID Numbers:
- C3291032
First Posted:
Apr 24, 2020
Last Update Posted:
Jun 7, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable body surface area (BSA) identified at Baseline/Day 1 and new atopic dermatitis (AD) lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Period Title: Double-Blind Treatment | ||
| STARTED | 131 | 260 |
| COMPLETED | 108 | 245 |
| NOT COMPLETED | 23 | 15 |
| Period Title: Double-Blind Treatment | ||
| STARTED | 114 | 232 |
| COMPLETED | 113 | 232 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) | Total |
|---|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Total of all reporting groups |
| Overall Participants | 131 | 260 | 391 |
| Age, Customized (Count of Participants) | |||
| 2-11 Years |
69
52.7%
|
123
47.3%
|
192
49.1%
|
| 12-17 Years |
15
11.5%
|
25
9.6%
|
40
10.2%
|
| >=18 Years |
47
35.9%
|
112
43.1%
|
159
40.7%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
64
48.9%
|
122
46.9%
|
186
47.6%
|
| Male |
67
51.1%
|
138
53.1%
|
205
52.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
131
100%
|
260
100%
|
391
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
131
100%
|
260
100%
|
391
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 29 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Least Squares Mean (95% Confidence Interval) [Percent Change] |
-42.79
|
-59.92
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vehicle Twice a Day (BID), Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Mixed effect Model for Repeated Measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean of difference |
| Estimated Value | -17.13 | |
| Confidence Interval |
(2-Sided) 95% -25.98 to -8.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Crisaborole = Test Vehicle = Reference | |
| Title | Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to Day 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants who were randomized and received at least 1 confirmed dose of investigational product. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Participants With Adverse Events |
44.3
33.8%
|
46.2
17.8%
|
| Participants With Serious Adverse Events |
0.8
0.6%
|
0.4
0.2%
|
| Participants With Severe Adverse Events |
1.5
1.1%
|
0
0%
|
| Participants Discontinued From Study Due to Adverse Events |
0.8
0.6%
|
0
0%
|
| Title | Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who were randomized and received at least 1 confirmed dose of investigational product. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=participants evaluable for each row. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 126 | 258 |
| Hemoglobin (g/L) <0.8 x lower limit of normal (LLN) |
1.6
1.2%
|
0
0%
|
| Leukocytes (10^9/L) >1.5 x upper limit of normal (ULN) |
0
0%
|
0.4
0.2%
|
| Lymphocytes (10^9/L) <0.8 x LLN |
0.8
0.6%
|
0
0%
|
| Lymphocytes/Leukocytes (%) >1.2 x ULN |
3.2
2.4%
|
1.9
0.7%
|
| Neutrophils (10^9/L) <0.8 x LLN |
0
0%
|
0.4
0.2%
|
| Neutrophils (10^9/L) >1.2 x ULN |
0
0%
|
0.4
0.2%
|
| Neutrophils/Leukocytes (%) <0.8 x LLN |
3.2
2.4%
|
2.7
1%
|
| Basophils/Leukocytes (%) >1.2 x ULN |
4.8
3.7%
|
3.1
1.2%
|
| Eosinophils (10^9/L) >1.2 x ULN |
33.1
25.3%
|
31.1
12%
|
| Eosinophils/Leukocytes (%) >1.2 x ULN |
29.8
22.7%
|
33.1
12.7%
|
| Monocytes (10^9/L) >1.2 x ULN |
0
0%
|
0.4
0.2%
|
| Monocytes/Leukocytes (%) >1.2 x ULN |
1.6
1.2%
|
1.6
0.6%
|
| Bicarbonate (mmol/L) <0.9 x LLN |
0.8
0.6%
|
0.8
0.3%
|
| Glucose (mmol/L) >1.5 x ULN |
0
0%
|
0.8
0.3%
|
| Title | Percentage of Participants With Clinically Significant Changes From Baseline in Vital Signs |
|---|---|
| Description | 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 |
| Time Frame | Baseline up to Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Analysis Set included all participants who were randomized and received at least 1 confirmed dose of investigational product. Overall number of participants analyzed=participants evaluable for this outcome measure. Number analyzed=participants evaluable for this outcome measure for each row. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 129 | 259 |
| Diastolic Blood Pressure (mmHg) Value <50 mmHg |
7.8
6%
|
7.3
2.8%
|
| Diastolic Blood Pressure (mmHg) Change ≥20mmHg increase |
2.3
1.8%
|
3.5
1.3%
|
| Diastolic Blood Pressure (mmHg) Change ≥20mmHg decrease |
3.9
3%
|
3.1
1.2%
|
| Pulse Rate (bpm) Value >120 beats per minute (bpm) |
2.3
1.8%
|
1.9
0.7%
|
| Systolic Blood Pressure (mmHg) Value <90mmHg |
23.3
17.8%
|
26.3
10.1%
|
| Systolic Blood Pressure (mmHg) Change ≥30mmHg increase |
0
0%
|
2.3
0.9%
|
| Systolic Blood Pressure (mmHg) Change ≥30mmHg decrease |
3.1
2.4%
|
0.8
0.3%
|
| Title | Percentage of Participants Achieving Improvement in Investigator's Static Global Assessment (ISGA) at Day 29 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Number (95% Confidence Interval) [Percentage of Participants] |
28.5
21.8%
|
41.4
15.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vehicle Twice a Day (BID), Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0124 |
| Comments | ||
| Method | normal approximation to response rates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 12.9 | |
| Confidence Interval |
(2-Sided) 95% 2.8 to 23.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Crisaborole = Test Vehicle = Reference | |
| Title | Percentage of Participants Achieving Success in ISGA at Day 29 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Number (95% Confidence Interval) [Percentage of Participants] |
15.9
12.1%
|
27.6
10.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vehicle Twice a Day (BID), Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0078 |
| Comments | ||
| Method | normal approximation to response rates | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 11.7 | |
| Confidence Interval |
(2-Sided) 95% 3.1 to 20.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Crisaborole = Test Vehicle = Reference | |
| Title | Change From Baseline in Peak Pruritus Numeric Rating Scale (NRS) at Week 4-for Participants ≥12 Years |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 62 | 137 |
| Least Squares Mean (95% Confidence Interval) [Units on a Scale] |
-0.79
|
-1.58
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vehicle Twice a Day (BID), Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | ||
| Method | Mixed effect Model for Repeated Measures | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean of Difference |
| Estimated Value | -0.79 | |
| Confidence Interval |
(2-Sided) 95% -1.26 to -0.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Crisaborole = Test Vehicle = Reference | |
| Title | Percentage of Participants Achieving Success in ISGA Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Day 8 |
0.0
0%
|
4.8
1.8%
|
| Day 15 |
4.9
3.7%
|
11.6
4.5%
|
| Day 22 |
10.8
8.2%
|
18.1
7%
|
| Day 29 |
15.9
12.1%
|
27.6
10.6%
|
| Title | Percentage of Participants Achieving Improvement in ISGA Over Time |
|---|---|
| Description | 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) . |
| Time Frame | Baseline, Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Day 8 |
7.8
6%
|
16.8
6.5%
|
| Day 15 |
18.3
14%
|
25.6
9.8%
|
| Day 22 |
25.1
19.2%
|
32.3
12.4%
|
| Day 29 |
28.5
21.8%
|
41.4
15.9%
|
| Title | Percent Change From Baseline in EASI Total Score Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Day 8 |
-21.43
|
-36.65
|
| Day 15 |
-37.15
|
-49.65
|
| Day 22 |
-42.92
|
-55.05
|
| Day 29 |
-42.79
|
-59.92
|
| Title | Change From Baseline in Percent Body Surface Area (%BSA) Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Day 8 |
-1.75
|
-5.12
|
| Day 15 |
-3.31
|
-7.60
|
| Day 22 |
-4.38
|
-8.72
|
| Day 29 |
-4.81
|
-9.89
|
| Title | Percentage of Participants Achieving EASI-50 Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Day 8 |
18.5
14.1%
|
37.1
14.3%
|
| Day 15 |
32.7
25%
|
58.9
22.7%
|
| Day 22 |
42.2
32.2%
|
66.4
25.5%
|
| Day 29 |
49.4
37.7%
|
72.7
28%
|
| Title | Percentage of Participants Achieving EASI-75 Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 131 | 260 |
| Day 8 |
6.1
4.7%
|
11.2
4.3%
|
| Day 15 |
15.4
11.8%
|
26.3
10.1%
|
| Day 22 |
26.3
20.1%
|
38.2
14.7%
|
| Day 29 |
27.6
21.1%
|
46.4
17.8%
|
| Title | Change From Baseline in Peak Pruritus NRS Over Time-for Participants ≥12 Years |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 1, Week 2, Week 3, Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 62 | 137 |
| Week 1 |
-0.38
|
-0.94
|
| Week 2 |
-0.53
|
-1.26
|
| Week 3 |
-0.64
|
-1.41
|
| Week 4 |
-0.79
|
-1.58
|
| Title | Change From Baseline in Patient Reported Itch Severity Scale Over Time-for Participants ≥6 Years and <12 Years |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 1, Week 2, Week 3, Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥ 6 and <12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 36 | 81 |
| Week 1 |
-0.26
|
-0.51
|
| Week 2 |
-0.22
|
-0.70
|
| Week 3 |
-0.37
|
-0.78
|
| Week 4 |
-0.52
|
-0.86
|
| Title | Change From Baseline in Observer Reported Itch Severity Scale Over Time-for Participants <6 Years |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 1, Week 2, Week 3, Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged <6 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 33 | 42 |
| Week 1 |
-0.31
|
-1.03
|
| Week 2 |
-0.73
|
-1.68
|
| Week 3 |
-0.96
|
-1.79
|
| Week 4 |
-1.25
|
-1.95
|
| Title | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 15, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥16 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 49 | 117 |
| Day 15 |
-1.1
(4.02)
|
-1.7
(3.57)
|
| Day 29 |
-1.5
(4.67)
|
-1.8
(4.11)
|
| Title | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 15, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged 4-15 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 67 | 127 |
| Day 15 |
-1.3
(5.18)
|
-3.6
(4.64)
|
| Day 29 |
-1.8
(6.00)
|
-3.9
(5.37)
|
| Title | Change From Infants' Dermatitis Quality of Life Index (IDQOL) Total Score Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 15, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged 2-3 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 15 | 16 |
| Day 15 |
-1.3
(3.34)
|
-3.0
(3.30)
|
| Day 29 |
-0.7
(3.86)
|
-4.3
(4.44)
|
| Title | Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) Score Over Time |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 15, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged 2-17 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 84 | 148 |
| Day 15 |
-0.5
(3.87)
|
-2.4
(4.66)
|
| Day 29 |
-2.1
(4.86)
|
-3.0
(5.22)
|
| Title | Change From Baseline in Patient-Oriented Eczema Measure (POEM) Over Time in Participants ≥12 Years |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 15, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 62 | 137 |
| Day 15 |
-1.8
(5.25)
|
-5.4
(5.19)
|
| Day 29 |
-3.3
(5.38)
|
-5.7
(6.32)
|
| Title | Change From Baseline in POEM Over Time in Participants ≥2 Years and <12 Years |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Day 15, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥2 and <12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 69 | 123 |
| Day 15 |
-2.5
(5.17)
|
-6.7
(6.09)
|
| Day 29 |
-3.8
(5.33)
|
-7.7
(5.41)
|
| Title | Change From Baseline in Weekly Average of Patient Global Impression of Severity (PGIS) Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 1, Week 2, Week 3, Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 62 | 137 |
| Week 1 |
-0.24
(0.511)
|
-0.43
(0.649)
|
| Week 2 |
-0.26
(0.692)
|
-0.60
(0.836)
|
| Week 3 |
-0.38
(0.871)
|
-0.66
(0.913)
|
| Week 4 |
-0.44
(0.965)
|
-0.71
(1.028)
|
| Title | Patient Global Impression of Change (PGIC) Score |
|---|---|
| Description | 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'. |
| Time Frame | Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 62 | 137 |
| Day 8 |
3.3
(1.05)
|
2.6
(1.10)
|
| Day 15 |
3.2
(1.10)
|
2.6
(1.07)
|
| Day 22 |
3.0
(1.19)
|
2.6
(1.04)
|
| Day 29 |
2.9
(1.21)
|
2.5
(1.12)
|
| Title | Change From Baseline in Weekly Average of Observer Reported Global Impression of Severity (OGIS) Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 1, Week 2, Week 3, Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥2 and <12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 69 | 123 |
| Week 1 |
-0.12
(0.593)
|
-0.62
(0.667)
|
| Week 2 |
-0.27
(0.617)
|
-0.93
(0.794)
|
| Week 3 |
-0.41
(0.770)
|
-1.03
(0.822)
|
| Week 4 |
-0.54
(0.854)
|
-1.14
(0.893)
|
| Title | Observer Reported Global Impression of Change (OGIC) Score |
|---|---|
| Description | 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'. |
| Time Frame | Day 8, Day 15, Day 22, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Overall number of participants analyzed included all participants randomized and dispensed study drug and aged ≥2 and <12 years. Participants were assigned to the randomized treatment regardless of what treatment was received. Number analyzed=participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) |
|---|---|---|
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. |
| Measure Participants | 69 | 123 |
| Day 8 |
3.0
(1.08)
|
2.3
(0.81)
|
| Day 15 |
3.0
(1.10)
|
2.3
(0.92)
|
| Day 22 |
2.9
(1.16)
|
2.4
(0.99)
|
| Day 29 |
2.8
(1.07)
|
2.2
(1.05)
|
Adverse Events
| Time Frame | Baseline up to Day 60 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who were randomized and received at least 1 confirmed dose of investigational product. | |||
| Arm/Group Title | Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) | ||
| Arm/Group Description | Vehicle was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | Crisaborole 2% was applied BID for 28 days to the Treatable BSA identified at Baseline/Day 1 and new AD lesions that appear after the Baseline/Day 1. | ||
All Cause Mortality |
||||
| Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/131 (0%) | 0/260 (0%) | ||
Serious Adverse Events |
||||
| Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/131 (0.8%) | 1/260 (0.4%) | ||
| Investigations | ||||
| Myocardial necrosis marker increased | 1/131 (0.8%) | 0/260 (0%) | ||
| Nervous system disorders | ||||
| Carpal tunnel syndrome | 0/131 (0%) | 1/260 (0.4%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Vehicle Twice a Day (BID) | Crisaborole 2% Twice a Day (BID) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 43/131 (32.8%) | 101/260 (38.8%) | ||
| General disorders | ||||
| Application site discolouration | 1/131 (0.8%) | 9/260 (3.5%) | ||
| Application site irritation | 1/131 (0.8%) | 3/260 (1.2%) | ||
| Application site pain | 5/131 (3.8%) | 34/260 (13.1%) | ||
| Application site paraesthesia | 1/131 (0.8%) | 7/260 (2.7%) | ||
| Application site urticaria | 0/131 (0%) | 3/260 (1.2%) | ||
| Pyrexia | 1/131 (0.8%) | 6/260 (2.3%) | ||
| Infections and infestations | ||||
| Conjunctivitis | 2/131 (1.5%) | 3/260 (1.2%) | ||
| Folliculitis | 6/131 (4.6%) | 8/260 (3.1%) | ||
| Gastroenteritis | 0/131 (0%) | 3/260 (1.2%) | ||
| Nasopharyngitis | 4/131 (3.1%) | 9/260 (3.5%) | ||
| Otitis media acute | 2/131 (1.5%) | 1/260 (0.4%) | ||
| Pharyngitis | 2/131 (1.5%) | 3/260 (1.2%) | ||
| Tonsillitis | 0/131 (0%) | 3/260 (1.2%) | ||
| Upper respiratory tract infection | 4/131 (3.1%) | 9/260 (3.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Epistaxis | 0/131 (0%) | 3/260 (1.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acne | 3/131 (2.3%) | 4/260 (1.5%) | ||
| Dermatitis atopic | 15/131 (11.5%) | 20/260 (7.7%) | ||
| Dermatitis contact | 1/131 (0.8%) | 6/260 (2.3%) | ||
| Miliaria | 2/131 (1.5%) | 0/260 (0%) | ||
| Pruritus | 3/131 (2.3%) | 0/260 (0%) | ||
| Urticaria | 1/131 (0.8%) | 3/260 (1.2%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT04360187
Other Study ID Numbers:
- C3291032
First Posted:
Apr 24, 2020
Last Update Posted:
Jun 7, 2022
Last Verified:
May 1, 2022