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JAK1 Inhibitor With Medicated Topical Therapy in Adolescents With Atopic Dermatitis (JADE TEEN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03796676
Recruitment Status : Recruiting
First Posted : January 8, 2019
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a randomized, double blind, placebo controlled, parallel group, Phase 3 study to evaluate the efficacy and safety of PF 04965842 in adolescent participants 12 to <18 years of age with moderate to severe AD.

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Drug: Placebo Drug: PF-04965842 Drug: PF04965842 Phase 3

Detailed Description:

This is a randomized, double blind, placebo controlled, parallel group, Phase 3 study to evaluate the efficacy and safety of PF 04965842 in adolescent participants 12 to <18 years of age with moderate to severe AD. Participants will be screened within 28 days prior to the first dose of study intervention to confirm study eligibility. Subjects must have moderate-severe AD involving at least 10% Body Surface Area (BSA); an Investigator Global Assessment (IGA) score of at least 3; an Eczema Area Severity Index (EASI) of at least 16 and Peak Pruritus Numerical Rating Score (NRS) of at least 4 on baseline/Day 1. Eligible subjects will be randomized at the Baseline/Day 1 visit. Approximately 225 participants will be randomized in a 1:1:1 ratio to receive once daily PF 04965842 at 200 mg, 100 mg, or placebo for 12 weeks. Randomization will be stratified by baseline disease severity (moderate [IGA = 3] vs. severe [IGA = 4] AD). The investigational products will be administered QD for 12 weeks. Background therapy (medicated and non-medicated topical therapy) must be applied BID for the duration of the treatment period. The co-primary efficacy endpoints are an IGA score of clear (0) or almost clear (1) with a reduction from baseline of greater than 2 points at Week 12 AND an at least 75% improvement of the EASI score (EASI-75) at week 12. Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment. Scheduled clinic or telephone study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8 (by phone), Day 15, Day 29, Day 43 (by phone), Day 57, Day 85 (End of treatment/Early termination), Day 113 (End of Study). Participants discontinuing early from the study will undergo a 4 week follow up period.

This study includes an immunogenicity sub study integrated into the last 4 weeks of the main study treatment period. At Week 8, up to approximately 90 participants (up to approximately 30 in each treatment arm) who have completed 8 weeks of treatment with study intervention will receive a tetanus, diphtheria and acellular pertussis combination vaccine (Tdap), and collection of blood samples for the evaluation of immunogenicity at Weeks 8 and 12. Participants of this sub study will complete all other protocol specified procedures in the main study.

At the end of the 12 week study treatment, qualified participants completing the study will have the option to enter the long term extension (LTE) study B7451015.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 CO-ADMINISTERED WITH BACKGROUND MEDICATED TOPICAL THERAPY IN ADOLESCENT PARTICIPANTS 12 TO <18 YEARS OF AGE WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS
Actual Study Start Date : February 18, 2019
Estimated Primary Completion Date : April 9, 2020
Estimated Study Completion Date : April 9, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

Experimental: PF-04965842 100 mg QD
active
Drug: PF-04965842
100 mg QD

Experimental: PF-04965842 200 mg QD
active
Drug: PF04965842
200 mg QD




Primary Outcome Measures :
  1. Change from baseline response based on IGA score of 0 or 1 and a reduction from baseline of at least 2 points. [ Time Frame: Day 1 (Baseline), Week 12 (end of treatment/early termination). ]
    Investigator's Global Assessment (IGA) assessed the severity of AD (except scalp, palms and soles) on a 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (AD is cleared, except for any residual discoloration, post-inflammatory hyperpigmentation and/or hypopigmentation), 1= almost clear, 2= mild , 3= moderate and 4= severe. Percentage of participants with an ISGA score of 0 or 1 were reported.

  2. Change from baseline response based on the Eczema Area and Severity Index of more than 75% improvement from baseline (EASI-75). [ Time Frame: Day 1 (Baseline), Week 12 (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.


Secondary Outcome Measures :
  1. Change from baseline response based on at least 4 points improvement in the Peak Pruritus NRS [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 12 (end of treatment/early termination). ]
    Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point Numeric Rating Score (NRS) where 0 is no pruritus and 10 is most severe possible pruritus. Change: score at observation minus score at baseline.

  2. Change from baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) total score [ Time Frame: Day 1 (Baseline), Week 12 (end of treatment/early termination). ]
    The PSAAD is a daily patient reported symptom diary. The version is a 15 item questionnaire that includes 11 items developed to measure symptoms of AD, capturing those identified by patients to be most important, based on a 24 hour recall. Analysis of the PSAAD will be based solely on these 11 items.

  3. Change from baseline response based on at least 4 points improvement in the Peak Pruritus NRS [ Time Frame: Day 1 (Baseline), Days 2-14, Week 8, Week 16 (end of study). ]
    Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point Numeric Rating Score (NRS) where 0 is no pruritus and 10 is most severe possible pruritus. Change: score at observation minus score at baseline.

  4. Time to achieve at least 4 points improvement in the Peak Pruritus NRS from baseline [ Time Frame: Day 1 (Baseline), Days 2-14, Day 15 (week 2) ]
    Participant-rated pruritus score of lesions rated the severity of pruritus suffered in the past 24 hours on an 11-point Numeric Rating Score (NRS) where 0 is no pruritus and 10 is most severe possible pruritus. Change: score at observation minus score at baseline.

  5. Change from baseline response based on the Eczema Area and Severity Index of more than 75% improvement from baseline (EASI-75). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 16 (end of study). ]
    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.

  6. Change from baseline response based on Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and a reduction from baseline of at least 2 points. [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 16 (end of study). ]
    Investigator's Global Assessment (IGA) assessed the severity of AD (except scalp, palms and soles) on a 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (AD is cleared, except for any residual discoloration, post-inflammatory hyperpigmentation and/or hypopigmentation), 1= almost clear, 2= mild , 3= moderate and 4= severe. Percentage of participants with an ISGA score of 0 or 1 were reported.

  7. Change from baseline response based on the Eczema Area and Severity Index of more than 50% improvement from baseline (EASI-50). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    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.

  8. Change from baseline response based on the Eczema Area and Severity Index of more than 90% improvement from baseline (EASI-90). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    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.

  9. Change from baseline response based on the Eczema Area and Severity Index of 100% improvement from baseline (EASI-100). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    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.

  10. Change from baseline in the percentage Body Surface Area (%BSA) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    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 adducted together, is approximately 1% of the subject's BSA, regardless of the subject's age. BSA in handprints across 4 body regions assessed as part of the EASI assessment.

  11. Proportion of participants with affected BSA <5% [ Time Frame: Day 1 (Baseline), Week 12 (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 adducted together, is approximately 1% of the subject's BSA, regardless of the subject's age. BSA in handprints across 4 body regions assessed as part of the EASI assessment.

  12. Change from baseline response based on more than 50% improvement in Scoring Atopic Dermatitis (SCORAD50). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    SCORAD is a validated scoring index for AD, which combines A: extent (0-100), B: severity (0-18), and C: subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103).

  13. Change from baseline response based on more than 75% improvement in Scoring Atopic Dermatitis (SCORAD75). [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    SCORAD is a validated scoring index for AD, which combines A: extent (0-100), B: severity (0-18), and C: subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103).

  14. Change from baseline in SCORAD subjective assessments of itch and sleep loss. [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    SCORAD is a validated scoring index for AD, which combines A: extent (0-100), B: severity (0-18), and C: subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10). The SCORAD for an individual is calculated by the formula: A/5 + 7B/2 + C (can range from 0 to 103). Only the subjective symptoms (0-20) based on pruritus and sleep loss, each scored (0-10), will be assessed.

  15. Change from baseline in Children's Dermatology Life Quality Index (CDLQI) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    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.

  16. Change from baseline in the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    HADS is a participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.

  17. Change from baseline in Patient Oriented Eczema Measure (POEM) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    The POEM is a validated 7 item PRO measure used to assess the impact of AD recalled over the past week. It contains 7 symptom based questions with responses rating number of days each symptom was experienced over the past week, ranging from 0 (no days) to 4 (every day), with a maximum score of 28.

  18. Change from baseline in Dermatitis Family Impact (DFI) questionnaire [ Time Frame: Day 1 (Baseline), Week 12 (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.

  19. Change from baseline of Patient Global Assessment (PtGA) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    The PtGA asks the participant to evaluate the overall cutaneous disease at that point in time on a single item, 5 point scale. The same category labels used in the Investigator's Global Assessment will be used for the Patient Global Assessment, ie, "severe (4)", "moderate (3)", "mild (2)", "almost clear (1)", and "clear (0)".

  20. Change from baseline of EuroQol Quality of Life 5 Dimension Youth Scale (EQ-5D-Y) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    The EQ-5D-Y is a validated, standardized, generic instrument that is the most widely used preference based health related quality of life questionnaire in cost effectiveness and health technologies assessment (HTA). The EQ-5D-Y is a version of the instrument specifically developed and validated for use by youths age 12 through 17 years. Components assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. Score scale ranged from 1 (minimum) to 3 (maximum). Higher scores indicated worse health condition.

  21. Change from baseline of Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds FACIT-F) [ Time Frame: Day 1 (Baseline), Week 2, Week 4, Week 8, Week 12 (end of treatment/early termination), Week 16 (end of study). ]
    FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

  22. Incidence of treatment emergent adverse events [ Time Frame: From Screening through Week 16 (entire study) ]

    Incidence of treatment emergent AEs. An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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) and c) severe (AEs interferes significantly with participant's usual function).

    AE's 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 occurrence of AE's in a non-leading manner.


  23. Incidence of Serious Adverse Events (SAE's) [ Time Frame: From Screening through Week 16 (entire study) ]
    Incidence of SAEs, eg. an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  24. Incidence of AEs leading to discontinuation; [ Time Frame: From Screening through Week 16 (entire study) ]
    Counts of participants who had adverse events leading to discontinuation.

  25. The incidence of clinical abnormalities and change from baseline in clinical laboratory values, ECG measurements, and vital signs. [ Time Frame: From Screening through Week 16 (entire study) ]
    Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). A 12-lead ECG was obtained after the participant had rested quietly for at least 10 minutes. Vital signs (pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance was determined at the investigator's discretion.

  26. Mean fold increase from baseline in concentrations of immunoglobulin G (IgG) against tetanus, diphtheria, and acellular pertussis combination vaccine (Tdap) [ Time Frame: Week 8 (sub-study baseline), Week 12 (end of treatment). ]

    Mean fold increase will be assessed from baseline (week 8) at 4 weeks post-vaccination in concentrations of IgG against:

    • Tetanus toxoid;
    • Diphtheria toxoid;
    • Pertussis toxoid;
    • Pertactin (PRN);
    • Filamentous hemagglutinin (FHA);
    • Fimbriae types 2 and 3 (FIM).

  27. Plasma concentrations of PF 04965842 in adolescent participants 12 to <18 years of age with moderate to severe AD. [ Time Frame: Week 8, Week 12 (end of treatment). ]
    Plasma concentrations of PF-04965842 2 hours prior to dosing on Day 57 (week 8) and 2 hours post-dosing on Day 85 (Week 12)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged between 12 and to 17 with a minimum body weight of 40 kg
  • Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate to severe disease (>= the following scores: BSA 10%, IGA 3, EASI 16, Pruritus NRS severity 4)

Exclusion Criteria:

  • Acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation
  • Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
  • Prior treatment with JAK inhibitors
  • Other active non-AD inflammatory skin diseases or conditions affecting skin
  • Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, malignancies, current or history of certain infections, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
  • Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03796676


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

  Show 153 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03796676     History of Changes
Other Study ID Numbers: B7451036
JADE TEEN ( Other Identifier: Alias Study Number )
2018-003804-37 ( EudraCT Number )
First Posted: January 8, 2019    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Atopic Dermatitis, JAK1 inhibitor
Additional relevant MeSH terms:
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Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases