Dupilumab De-escalation in Pediatric Atopic Dermatitis

Study Overview
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Brief Summary
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This is a pilot investigator-blinded, randomized clinical trial to assess the feasibility of dupilumab treatment discontinuation or dose-reduction in children aged 1-17 years who have achieved sustained atopic dermatitis (AD) control on dupilumab.

Detailed Description
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Participants will be randomly assigned to one of three groups: discontinuation of dupilumab; reduction of dupilumab dose; or continuation of standard dupilumab dose. During the active study treatment period, participants will be asked to complete 5 study visits. At these visits, a physician will conduct a skin examination to assess atopic dermatitis (AD) severity and participants will complete questionnaires about their AD symptoms and severity. During the observational period, participants will be asked to complete questionnaires about their AD symptoms and medication use every twelve weeks, for a total of 3 follow-up contacts. The purpose of this study is to evaluate the feasibility and sustainability of reducing or discontinuing dupilumab in children with well-controlled AD.

Official Title
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Dupilumab De-escalation in Pediatric Atopic Dermatitis: A Pilot Trial

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Dupilumab - Discontinuation
* Drug: Dupilumab - Dose Reduction
* Drug: Dupilumab - Standard Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 1 to <18 years old, either sex, any race or ethnicity Provide signed informed consent by parent or legal guardian and informed assent if applicable Has a physician confirmed diagnosis of atopic dermatitis Has received dupilumab for at least 12 months for the treatment of atopic dermatitis Has had well-controlled atopic dermatitis on dupilumab within last 6 months (defined as POEM<=7, EASI<=7, or IGA<=2) Able to speak English Able and willing to adhere to all study procedures Exclusion Criteria: Taking concurrent systemic medication for atopic dermatitis (e.g., methotrexate, cyclosporine, tralokinumab, abrocitinib, upadacitinib, systemic corticosteroids) Using concurrent phototherapy for atopic dermatitis Taking dupilumab for a clinical indication other than atopic dermatitis (such as asthma or eosinophilic esophagitis) Poor control of atopic dermatitis Poor control of asthma or eosinophilic esophagitis Has used an investigational drug within 90 days or plan to use an investigational drug during the study period Does not have health insurance or will lose health insurance during the study period

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dupilumab - discontinuation<br>Participants will discontinue their dupilumab treatment for atopic dermatitis. | Drug: Dupilumab - Discontinuation<br>* Drug injections are discontinued.<br>* Other names: Dupixent;|
| Experimental: Dupilumab - dose reduction<br>Participants whose standard dupilumab dosing for atopic dermatitis is 200 mg or 300 mg every 2 weeks will decrease drug administration to every 4 weeks, and participants whose standard dupilumab dosing is 200 mg or 300 mg every 4 weeks will decrease administration to every 8 weeks. | Drug: Dupilumab - Dose Reduction<br>* The drug is given as a subcutaneous injection.<br>* Other names: Dupixent;|
| Experimental: Dupilumab - standard dosing<br>Participants will continue to receive standard maintenance dupilumab dosing for atopic dermatitis according to FDA labeling, as indicated below. Infants ≥6 months and Children <6 years: 5 to <15 kg: 200 mg every 4 weeks. 15 to <30 kg: 300 mg every 4 weeks Children ≥6 years and Adolescents ≤17 years: 15 to <30 kg: 300 mg every 4 weeks 30 to <60 kg: 200 mg every other week ≥60 kg: 300 mg every other week | Drug: Dupilumab - Standard Dose<br>* The drug is given as a subcutaneous injection.<br>* Other names: Dupixent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Successful Dose Reduction of Dupilumab | Successful de-escalation is defined as maintaining a reduced dose (i.e., less frequent administration) of dupilumab after initial de-escalation on week 0. Patients who require re-escalating the dose of dupilumab to standard dosing or adding other systemic treatments for their AD will be regarded as treatment failure. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Percentage of Participants with Successful Discontinuation of Dupilumab | Successful discontinuation is defined as maintaining discontinuation of dupilumab after initial discontinuation on week 0. Patients who require resumption of dupilumab or beginning other systemic treatments for their AD will be regarded as treatment failure. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Investigator's Global Assessment (IGA) Scores | IGA is a global clinical assessment scale to determine severity of AD and clinical response to treatment on a static 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on the degree of erythema and papulation/infiltration. The IGA score ranges from 0 to 4. Higher scores indicate greater severity of AD. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Eczema Area and Severity Index (EASI) Scores | The EASI score is used to evaluate severity of AD based on AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. The total EASI score ranges from 0 to 72. Higher scores indicate greater severity of AD. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient Oriented Eczema Measure (POEM) Scores | The POEM is a 7-item questionnaire to assess disease symptoms in children and adults with AD. It is composed of 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total POEM score ranges from 0 to 28. Higher scores indicate more severe disease and poor quality of life. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Itch questionnaire score | The PROMIS Itch questionnaire measures the extent to which patients experience problems with itchiness over the past 7 days using a 5-point Likert scale (1 = Never; 2 = Rarely; 3 = Sometimes; 4 = Often; and 5 = Almost Always). Higher scores reflect greater severity of experienced itch symptoms. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Problem questionnaire score | The PROMIS Sleep Problem questionnaire measures the extent to which patients experience problems with sleep over the past 7 days using a 5-point Likert scale (1 = Never; 2 = Almost never; 3 = Sometimes; 4 = Almost always; and 5 = Always). The sleep problems contain sleep disturbances (sleep quality, sleep onset, sleep continuity) and sleep-related impairment (perceptions of sleepiness during usual awake hours and reported impairments during the day associated with sleep problems or daytime sleepiness). Higher scores reflect greater severity of sleep problems. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety questionnaire score | The PROMIS Anxiety questionnaire measures the extent to which patients experience problems with anxiety over the past 7 days using a 5-point Likert scale (1 = Never; 2 = Almost never; 3 = Sometimes; 4 = Often; and 5 = Almost Always). The questionnaire includes fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), social/separation anxiety (fear or distress when separating from caregivers), and somatic symptoms related to arousal (racing heart, dizziness). Higher scores reflect greater severity of experienced anxiety symptoms. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Depressive Symptoms questionnaire score | The PROMIS Depressive Symptoms questionnaire measures the extent to which patients experience problems with depression over the past 7 days using a 5-point Likert scale (1 = Never; 2 = Almost never; 3 = Sometimes; 4 = Almost Always; and 5 = Always). The depressive symptoms include negative mood (sadness, guilt), views of self (self-criticism, worthlessness), and social cognition (loneliness, interpersonal alienation); decreased positive affect, anhedonia (loss of interest, inability to engage in play), and engagement. Higher scores reflect greater severity of experienced depressive symptoms. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function questionnaire score | The PROMIS Cognitive Function questionnaire measures the extent to which patients experience problems with cognitive function over the past 4 weeks using a 5-point Likert scale (1 = All of the time; 2 = Most of the time; 3 = Some of the time; 4 = A little of the time; and 5 = None of the time). The questionnaire includes difficulties in cognitive abilities (e.g., memory, attention, and decision making), and difficulties in the application of such abilities to everyday tasks (e.g., planning, organizing, calculating, remembering, and learning). Lower scores reflect greater impact on cognitive function. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health questionnaire score | The PROMIS Global Health questionnaire measures the extent to which patients experience problems with global health in general using a 5-point Likert scale (1 = Poor; 2 = Fair; 3 = Good; 4 = Fair; and 5 = Excellent). The questionnaire includes an overall evaluation of physical, mental health, and social health. Higher scores reflect a lower quality of global health. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity questionnaire score | The PROMIS Pain Intensity questionnaire measures the intensity of patients' pain due to their AD over the past 7 days using a 10 point scale, with 0 indicating No Pain and 10 indicating the worst pain possible. Higher raw scores reflect greater severity of experienced pain due to AD. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Children's Dermatology Life Quality Index (CDLQI) score | CDLQI is a 10-item questionnaire to assess the impact of skin problems on the quality of life of children between the ages of 4-16 years old over the last one week. Each question is evaluated on a 4-point scale: Not at all = 0, A Little = 1, Quite A Lot = 2, Very Much = 3. Higher scores indicate worse child-reported quality of life. CDLQI scores indicate the degree of severity burden on the quality of life: No effect = 0-1; Small effect = 2-6; Moderate effect = 7-12; Very large effect = 13-18; and Extremely large effect = 19-30. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Change in Family Dermatology Life Quality Index (FDLQI) score | FDLQI is a 10-item questionnaire to assess the impact of skin problems on the quality of life of families over the last one month. Each question is evaluated on a 4-point scale: Not at all = 0, A Little = 1, Quite A Lot = 2, Very Much = 3. Higher scores indicate worse quality of life. FDLQI scores indicate the degree of severity burden on the quality of life: No effect = 0-1; Small effect = 2-6; Moderate effect = 7-12; Very large effect = 13-18; and Extremely large effect = 19-30. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Changes in Utilization of Topical Medications for Atopic Dermatitis | Participants will provide a self-report of their daily utilization of topical medications (medication name, dose and frequency) using a paper-form Daily Diary. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) | 
| Adverse Events After Dupilumab Dose-reduction or Discontinuation | The number of participants who experience adverse events ≥ Grade 2 is based on the Common Terminology Criteria for Adverse Events (CTCAE). The CTCAE is generally graded as follows: Grade 1 - mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not needed; Grade 2 - moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3 - severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self care activities of daily living; Grade 4 - life-threatening consequences; urgent intervention indicated; Grade 5 - death related to adverse event. | From Baseline through Week 16 (active protocol phase) and Week 17 through Week 52 (observational phase) |