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A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD

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ClinicalTrials.gov Identifier: NCT03539601
Recruitment Status : Recruiting
First Posted : May 28, 2018
Last Update Posted : October 25, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE May 16, 2018
First Posted Date  ICMJE May 28, 2018
Last Update Posted Date October 25, 2019
Actual Study Start Date  ICMJE April 27, 2018
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2019)
  • Percent change from Baseline in the Eczema Area and Severity Index (EASI) total score at Day 29. [ Time Frame: Day 1 (Baseline), Day 29 (end of treatment/early termination). ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Screening ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 1 (Baseline) ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 8 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 15 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 22 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 29 (end of treatment/early termination) ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 43 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 60 (end of study) ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with clinically significant change from baseline in vital signs [ Time Frame: Screening, Day 1 (Baseline), Day 29 (end of treatment/early termination) ]
    Vital sign measurements (temperature, respiratory rate, pulse rate and blood pressure) should be performed with the subject in the seated or lying position and after the subject has been sitting or lying calmly for a minimum of 5 minutes. The position of recording must be consistent within subject through-out the study. On study day visits when clinical laboratory tests are performed, assessment of vital signs should precede blood draw.
  • Number of subjects with clinically significant change from baseline in clinical laboratory parameters. [ Time Frame: Screening, Day 1 (Baseline), Day 29 (end of treatment/early termination) ]
    Laboratory parameters include: Hematology (Hemoglobin, Hematocrit, Red blood cell count, Platelet count White blood cell count [% and absolute], Neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes) chemistry (Blood urea nitrogen/Urea, Glucose (non fasting), Creatinine, Sodium, Potassium, Chloride, Bicarbonate or Total CO2, Alanine aminotransferase , Aspartate aminotransferase , Total bilirubin Alkaline phosphatase, Albumin, Total protein). Clinical significance of laboratory parameters will be determined at the investigator's discretion.
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
  • Percent change from Baseline in the Eczema Area and Severity Index (EASI) total score at Day 29. [ Time Frame: Day 1 (Baseline), Day 29 (end of treatment/early termination). ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Screening ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 1 (Baseline) ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 8 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 15 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 22 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 29 (end of treatment/early termination) ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 36 ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with incidence of treatment emergent adverse events and serious adverse events. [ Time Frame: Day 60 (end of study) ]
    Incidence of treatment emergent AEs and SAEs. This includes local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. The investigator is to record all directly observed AE's and all AE's spontaneously reported by the subject (or subject's legal guardian). In addition, each study subject (or subject's legal guardian) will be questioned about the occurence of AE's in a non-leading manner.
  • Number of subjects with clinically significant change from baseline in vital signs [ Time Frame: Screening, Day 1 (Baseline), Day 29 (end of treatment/early termination) ]
    Vital sign measurements (temperature, respiratory rate, pulse rate and blood pressure) should be performed with the subject in the seated or lying position and after the subject has been sitting or lying calmly for a minimum of 5 minutes. The position of recording must be consistent within subject through-out the study. On study day visits when clinical laboratory tests are performed, assessment of vital signs should precede blood draw.
  • Number of subjects with clinically significant change from baseline in clinical laboratory parameters. [ Time Frame: Screening, Day 1 (Baseline), Day 29 (end of treatment/early termination) ]
    Laboratory parameters include: Hematology (Hemoglobin, Hematocrit, Red blood cell count, Platelet count White blood cell count [% and absolute], Neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes) chemistry (Blood urea nitrogen/Urea, Glucose (non fasting), Creatinine, Sodium, Potassium, Chloride, Bicarbonate or Total CO2, Alanine aminotransferase , Aspartate aminotransferase , Total bilirubin Alkaline phosphatase, Albumin, Total protein). Clinical significance of laboratory parameters will be determined at the investigator's discretion.
Change History Complete list of historical versions of study NCT03539601 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2019)
  • Percent change from baseline in EASI total score by scheduled timepoints except Day 29. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Achievement of success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 1 (Baseline) ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 8 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 15 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 22 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 29 (end of treatment/early termination). ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 1 (Baseline) ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 8 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 15 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 22 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 29 (end of treatment/early termination) ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Achievement of EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 1 (Baseline) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. The endpoint is defined as the proportion of subjects with improvement of ≥75% in EASI score from baseline.
  • Achievement of EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 8 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Achievement of EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 15 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Achievement of EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 22 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Achievement of EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 29 (end of treatment/early termination) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Change from Baseline in % BSA by scheduled time points. [ Time Frame: Screening, Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The number of handprints of AD skin in a body region can be used to determine the extent (%) to which a body region is involved with atopic dermatitis. The area represented by the palmar surface of the subject's hand with all five digits adductedtogether, is approximately 1% of the subject's BSA, regardless of hte subject's age.
  • Change from Baseline in Dermatitis Family Impact Questionnaire (DFI) (Completed by parent/caregiver of Subjects 2-17 years) by scheduled time points. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The DFI is a 10-item disease questionnaire that measures the impact of having a child with AD on family quality of life. It is completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question is scored on a 4-point scale ranging from 0 (good) to 3 (worst), where higher scores indicated worst quality of life of family. The DFI total score is the sum of individual scores of the 10 questions and ranges from 0 (good) to 30 (worst), where higher DFI scores indicated worst quality of life of family.
  • Change from Baseline in Dermatology Life Quality Index (DLQI) (for Subjects 16 years and older), by scheduled time points. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The DLQI is a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question is evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants.
  • Time to EASI75. [ Time Frame: Day 1 (Baseline) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 8 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 15 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 22 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 29 (end of treatment/early termination) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Change from Baseline in Childrens Dermatology Life Quality Index (CDLQI) (for Subjects 4-15 years and older, completed by the subject with the help the caregiver, if needed), by scheduled time points. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The CDLQI is a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question is evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants.
  • Change from Baseline in Peak Pruritus Numerical Rating Scale (NRS) for subjects >12 years by scheduled time points. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination) ]
    Participant-rated pruritus score of the severity of pruritus due to AD, suffered in the past 24 hours on an 11-point Numeric Rating Score (NRS) where 0 is no itch and 10 is worst itch imaginable. Change: score at observation minus score at baseline.
  • Time to ≥2 point improvement from Baseline in Peak Pruritus NRS for subjects >12 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination) ]
    Time to improvement in pruritus is defined as the time interval between the administration of first dose of study drug till the first documentation of ≥2 point improvement in pruritus.
  • Time to ≥3 point improvement from Baseline in Peak Pruritus NRS for subjects >12 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Time to improvement in pruritus is defined as the time interval between the administration of first dose of study drug till the first documentation of ≥3 point improvement in pruritus.
  • Achievement of ≥2 point improvement from Baseline in Peak Pruritus NRS for subjects >12 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Proportion of subjects with documented ≥2 point improvement in pruritus.
  • Achievement of ≥3 point improvement from Baseline in Peak Pruritus NRS for subjects >12 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Proportion of subjects with documented ≥3 point improvement in pruritus.
  • Change from Baseline in Itch Severity Scale by scheduled time points for subjects 6-11 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Participant-rated itch score of the severity of itch due to AD suffered today, where 0 is Not itchy and 4 is Very itchy. Change: score at observation minus score at baseline.
  • Change from Baseline in Observer Reported Itch Severity Scale - for subjects <6 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Observer-rated itch score of the severity of itch due to AD, suffered in the past 24 hours on an 11-point observer Itch Severity Numeric Rating Score (NRS) where 0 is no itch and 10 is worst itch imaginable. Change: score at observation minus score at baseline.
  • Time ≥2 point to improvement from Baseline in Observer Reported Itch Severity Scale - for subjects <6 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Time to improvement in itch is defined as the time interval between the administration of first dose of study drug till the first documentation of ≥2 point improvement in itch.
  • Time ≥3 point to improvement from Baseline in Observer Reported Itch Severity Scale - for subjects <6 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Time to improvement in itch is defined as the time interval between the administration of first dose of study drug till the first documentation of ≥3 point improvement in itch.
  • Achievement of ≥2 point improvement from Baseline in Observer Reported Itch Severity Scale - for subjects <6 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Proportion of subjects with documented ≥2 point improvement in itch.
  • Achievement of ≥3 point improvement from Baseline in Observer Reported Itch Severity Scale - for subjects <6 years. [ Time Frame: Once Daily from Day 1 (Baseline) to Day 29 (end of treatment/early termination). ]
    Proportion of subjects with documented ≥3 point improvement in itch.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
  • Percent change from baseline in EASI total score by scheduled timepoints except Day 29. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Proportion of subjects achieving success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 1 (Baseline) ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects achieving success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 8 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects achieving success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 15 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects achieving success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 22 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects achieving success in the Investigator's Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2 grade improvement from Baseline) by scheduled time points. [ Time Frame: Day 29 (end of treatment/early termination). ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects with ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 1 (Baseline) ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects with ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 8 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects with ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 15 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects with ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 22 ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of subjects with ISGA score of clear (0) or almost clear (1) by scheduled time points. [ Time Frame: Day 29 (end of treatment/early termination) ]
    ISGA assessed the severity of AD (except scalp) 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).
  • Proportion of patients with EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 1 (Baseline) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. The endpoint is defined as the proportion of subjects with improvement of ≥75% in EASI score from baseline.
  • Proportion of patients with EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 8 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Proportion of patients with EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 15 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Proportion of patients with EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 22 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Proportion of patients with EASI75 (75% improvement from Baseline) by scheduled time points. [ Time Frame: Day 29 (end of treatment/early termination) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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.
  • Change from Baseline in % BSA by scheduled time points. [ Time Frame: Screening, Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The number of handprints of AD skin in a body region can be used to determine the extent (%) to which a body region is involved with atopic dermatitis. The area represented by the palmar surface of the subject's hand with all five digits adductedtogether, is approximately 1% of the subject's BSA, regardless of hte subject's age.
  • Change from Baseline in Dermatitis Family Impact Questionnaire (DFI) (Completed by parent/caregiver of Subjects 2-17 years) by scheduled time points. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The DFI is a 10-item disease questionnaire that measures the impact of having a child with AD on family quality of life. It is completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question is scored on a 4-point scale ranging from 0 (good) to 3 (worst), where higher scores indicated worst quality of life of family. The DFI total score is the sum of individual scores of the 10 questions and ranges from 0 (good) to 30 (worst), where higher DFI scores indicated worst quality of life of family.
  • Change from Baseline in Dermatology Life Quality Index (DLQI) (for Subjects 16 years and older), by scheduled time points. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The DLQI is a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question is evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants.
  • Time to EASI75. [ Time Frame: Day 1 (Baseline) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 8 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 15 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 22 ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Time to EASI75. [ Time Frame: Day 29 (end of treatment/early termination) ]
    The Eczema Area and Severity Index (EASI) quantifies the severity of a subject'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. Time to improvement in EASI75 is defined the time interval between the administration of first dose of study drug till improvement of ≥75% in EASI score.
  • Change from Baseline in Childrens Dermatology Life Quality Index (CDLQI) (for Subjects 4-15 years and older, completed by the subject with the help the caregiver, if needed), by scheduled time points. [ Time Frame: Day 1 (Baseline), Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination) ]
    The CDLQI is a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question is evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants.
Current Other Pre-specified Outcome Measures
 (submitted: October 23, 2019)
  • Change in epidermal thickness (Primary Sub-Study Endpoint) [ Time Frame: Baseline/Day 1 to Day 29 ]
  • Change in epidermal thickness (Secondary Sub-Study Endpoints) [ Time Frame: Baseline/Day 1 to all sub-study time points except Day 29 (Days 8, 15, 22, and 60) ]
  • Intrasubject difference of change in epidermal thickness between the non-lesional target skin site and the OCT AD lesional target skin site (Secondary Sub-Study Endpoints) [ Time Frame: Baseline to Days 8, 15, 22, 29 and 60 ]
  • Percentage change in TEWL (Secondary Sub-Study Endpoints) [ Time Frame: Baseline/Day 1 at Days 8, 15, 22, 29 and 60 ]
  • Change in skin biomarkers of Atopic Dermatitis (Secondary Sub-Study Endpoints) [ Time Frame: Change from Baseline/Day 1 in skin biomarkers of AD at Day 15 and Day 29 ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD
Official Title  ICMJE A PHASE 3B/4, MULTICENTER, RANDOMIZED, ASSESSOR BLINDED, VEHICLE AND ACTIVE (TOPICAL CORTICOSTEROID AND CALCINEURIN INHIBITOR) CONTROLLED, PARALLEL GROUP STUDY OF THE EFFICACY, SAFETY, AND LOCAL TOLERABILITY OF CRISABOROLE OINTMENT, 2% IN PEDIATRIC AND ADULT SUBJECTS (AGES 2 YEARS AND OLDER) WITH MILD TO MODERATE ATOPIC DERMATITIS
Brief Summary

This 4-week study will evaluate the safety and efficacy of crisaborole ointment 2%; crisaborole vehicle; topical corticosteroid and topical calcineurin inhibitor, applied twice daily (BID) in subjects who are at least 2 years of age with mild-moderate AD.

A Sub-Study of Optical Coherence Tomography and Biomarkers in Subjects ages 2 to <18 years old, with Mild to Moderate Atopic Dermatitis, treated with Crisaborole Ointment, 2% or Crisaborole Vehicle Ointment or Hydrocortisone Butyrate 0.1% Cream applied BID will also be conducted at select sites.

Detailed Description

Approximately 600 subjects will be enrolled in the study, of which at least 150 subjects aged 2-6; at least 140 subjects aged 7-11; at least 120 subjects aged 12-17 and up to 90 subjects will be adults. Subjects must have mild-moderate AD involving at least 5% treatable %BSA assessed on baseline/Day 1. Treatable %BSA will be defined as the percent of a subject's total body surface area that is AD involved, excluding the scalp.

Eligible subjects will be randomized at the Baseline/Day 1 visit. Randomization will be stratified by eligibility for TCS or TCI treatment as per national approved labels. Cohort 1 will be for subjects who are eligible for TCS therapy, and Cohort 2 will be for subjects who are not eligible for TCS therapy but eligible for TCI therapy. The investigational products will be applied BID for 28 days to the Treatable body surface area (BSA) identified at Baseline/Day 1.

The primary efficacy endpoint is the percent change from baseline in the Eczema Area and Severity Index (EASI) total score at Day 29.

For the efficacy comparison of crisaborole versus vehicle, subjects from both Cohort 1 and Cohort 2 are included in the analysis, adjusted for cohort effect. For the efficacy comparison of crisaborole versus TCS, only subjects from Cohort 1 are included in the analysis. For the comparison of crisaborole versus TCI, only subjects from Cohort 2 are included in the analysis.

Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment.

Scheduled study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8, Day 15, Day 22, Day 29 (End of treatment/Early termination), Day 43 or 14 Days after last dose if subject is terminated early from treatment. A follow up telephone call will be made by site staff to the subjects/subject's legally acceptable guardian(s) on Day 60 or at least 28 days after last dose if subject is terminated early from treatment. The Day 60 visit will be completed in the clinic for subjects enrolled in the OCT sub-study.

To further explore the benefit/risk of crisaborole ointment, 2%, a sub-study to evaluate differences in atrophic skin changes across study treatment groups in Cohort 1 will be conducted at select sites.

The sub-study will include obtaining Optical coherence tomography (OCT) imaging to evaluate atrophic changes in epidermal thickness during and after treatment with study investigational product in Cohort 1. This sub-study also provides an opportunity to explore differences in Transepidermal Water Loss (TEWL) and cutaneous inflammatory and barrier biomarkers associated with AD within the stratum corneum (SC) across treatment groups in Cohort 1. The Aquaflux (an evaporimeter) will be used in this sub-study to evaluate TEWL during and after treatment at select sub-study centers. Tape-strips will also be used in this sub-study to evaluate SC biomarkers from AD lesional and non-lesional skin.

This sub-study will include approximately 60 subjects from Cohort 1 that are enrolled in the main study (C3291037). Subjects will follow the main study assessments and visits as per the schedule of activities for the main study but will also follow additional procedures as described in the protocol. The telephone call at Day 60 in the main study is replaced with an in-clinic visit for sub-study participants.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The investigational products above are masked for appearance, and will be placed into identical cartons. Once removed from the product cartons, the investigational products could be discerned from each other based on commercial product tube shape/size and should only be handled by unblinded site personnel.

Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment.

Primary Purpose: Treatment
Condition  ICMJE Atopic Dermatitis
Intervention  ICMJE
  • Drug: Crisaborole ointment, 2%
    Applied twice a day (BID)
    Other Name: Eucrisa
  • Drug: Hydrocortisone butyrate cream, 0.1%
    Applied BID
    Other Name: Locoid 0.1%
  • Drug: Pimecrolimus cream, 1%
    Applied BID
    Other Name: Elidel
  • Drug: Crisaborole Vehicle
    Applied BID
Study Arms  ICMJE
  • Experimental: Crisaborole ointment, 2%
    This treatment arm will be administered both in Cohort 1 and Cohort 2.
    Intervention: Drug: Crisaborole ointment, 2%
  • Active Comparator: Hydrocortisone butyrate cream, 0.1%
    This treatment arm will be administered in Cohort 1 only.
    Intervention: Drug: Hydrocortisone butyrate cream, 0.1%
  • Active Comparator: Pimecrolimus cream, 1%
    This treatment arm will be administered in Cohort 2 only.
    Intervention: Drug: Pimecrolimus cream, 1%
  • Placebo Comparator: Crisaborole Vehicle
    This treatment arm will be administered both in Cohort 1 and Cohort 2.
    Intervention: Drug: Crisaborole Vehicle
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 16, 2018)
600
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2021
Estimated Primary Completion Date March 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Subjects in Cohort 1 are excluded if they have a contraindication for treatment with hydrocortisone butyrate cream 0.1%

Subjects in Cohort 2 are excluded if they have a contraindication for treatment with pimecrolimus cream, 1%

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Belgium,   Germany,   Italy,   Poland,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03539601
Other Study ID Numbers  ICMJE C3291037
2018-001043-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP