A Study to Assess Adverse Events and Change in Disease Activity Comparing Oral Upadacitinib to Subcutaneous Dupilumab in Children From 2 to Less Than 12 Years of Age With Moderate to Severe Atopic Dermatitis
NCT Number: NCT06461897
Acronym: Start Up
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Atopic Dermatitis
Interventions: DRUG: Upadacitinib|DRUG: Dupilumab
Sponsor: AbbVie
Sex: ALL
Age: CHILD
Enrollment: 675
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-19
Completion Date: 2030-06-22
Locations: Clearlyderm Dermatology - West Boca /ID# 266323, Boca Raton, Florida, 33428, United States|Cleaver Medical Group Dermatology /ID# 265099, Dawsonville, Georgia, 30534, United States|Aeroallergy Research Laboratory /ID# 267247, Savannah, Georgia, 31406, United States|Treasure Valley Medical Research /ID# 266838, Boise, Idaho, 83706, United States|Dawes Fretzin, LLC /ID# 265097, Indianapolis, Indiana, 46256, United States|Skin Specialists /ID# 266331, Omaha, Nebraska, 68144, United States|Arlington Research Center, Inc /ID# 266330, Arlington, Texas, 76011, United States|Progressive Clinical Research - San Antonio /ID# 267262, San Antonio, Texas, 78229, United States

Summary:
Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. Topical therapies applied over the skin may not be enough to control the AD in trial participants who require systemic anti-inflammatory treatment. This study compares upadacitinib to dupilumab in pediatric participants with moderate to severe AD who are candidates for systemic therapy. Adverse events and change in the disease activity will be assessed.

Upadacitinib is an approved drug for treating AD patients aged 12 or older. Participants will receive upadacitinib (given as daily dose) or dupilumab (given at label indicated dose every 2 or 4 weeks). Participants will be stratified depending on disease severity, age and response to previous treatment. There is 1 in 5 chance for participants to receive dupilumab during the randomized cohort. Approximately 675 participants aged 2 to less than 12 years of age will be enrolled in this study at approximately 150 sites worldwide. The study population (As defined by participants age or prior treatment) to be enrolled in the study is dependent on local regulatory requirement and/or agreement.

Participants will receive upadacitinib oral tablets once daily (or oral solution twice a day) for 160 weeks, or dupilumab as per its label for 52 weeks, and followed for 30 days.

There may be higher treatment burden for participants in this trial compared to their standard of care . Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by clinical assessments, blood tests, checking for side effects and completing questionnaires.

Primary Outcome Measures: Percentage of Participants Achieving a 75% Reduction from Baseline in Eczema Area and Severity Index Score (EASI 75), EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease., At Week 16
Secondary Outcome Measures: Percentage of participants achieving validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points, The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

* 0 - Clear: No inflammatory signs of AD;
* 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification;
* 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting;
* 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present;
* 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present., At Week 16|Percentage of participants achieving a 50% reduction from Baseline in EASI score (EASI 50), EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).

The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease., At Week 16|Percentage of participants achieving Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points, The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

* 0 - Clear: No inflammatory signs of AD;
* 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification;
* 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting;
* 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present;
* 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present., At Week 52|Percentage of participants achieving Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points, The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale:

* 0 - Clear: No inflammatory signs of AD;
* 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification;
* 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting;
* 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present;
* 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present., At Week 160|Percentage of participants achieving an improved (reduced) Patient Oriented Eczema Measure (POEM) of ≥ 4 points from from participants with POEM ≥ 4 at Baseline, The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference., At Week 16|Percentage of participants ≥ 4 years of age with a Baseline Children's Dermatology Life Quality Index (CDLQI) score of >1 achieving a CDLQI score of 0 or 1, The CDLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of dermatological disease symptoms and treatment on quality of life. The CDLQI has been validated for use in Participants 4 to 16 years of age. It consists of 10 questions assessing impact of skin diseases on different aspects of quality of life over the prior week. The CDLQI items include symptoms and feelings, daily activities, leisure, school, relationships, sleep, and treatment. Each item is scored on a 4-point scale: 0 = not at all; 1 = only a little; 2 = quite a lot; and 3 = very much. Item scores (0 to 3) are added to provide a total score range of 0 to 30; higher scores indicate greater impairment of quality of life., At Week 8|Percentage of participants ≥ 4 years of age with a Baseline Children's Dermatology Life Quality Index (CDLQI) score of >1 achieving a CDLQI score of 0 or 1, The CDLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of dermatological disease symptoms and treatment on quality of life. The CDLQI has been validated for use in Participants 4 to 16 years of age. It consists of 10 questions assessing impact of skin diseases on different aspects of quality of life over the prior week. The CDLQI items include symptoms and feelings, daily activities, leisure, school, relationships, sleep, and treatment. Each item is scored on a 4-point scale: 0 = not at all; 1 = only a little; 2 = quite a lot; and 3 = very much. Item scores (0 to 3) are added to provide a total score range of 0 to 30; higher scores indicate greater impairment of quality of life., At Week 16|Percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline, SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A negative change from Baseline indicates improvement., At Week 16|Use of topical or systemic rescue therapy from Baseline to Week 16, Baseline to Week 16|Number of days on rescue topical corticosteroid or topical calcineurin inhibitor from Baseline to Week 16, Baseline to Week 16|Percentage of participants achieving a EASI 75 response for low dose upadacitinib daily adult equivalent dose, EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\],

An EASI 75 response is defined as a 75% reduction (improvement) from Baseline in EASI score., At Week 16