A Phase 3, Open-label, Efficacy-Assessor-Blinded Study, Comparing the Safety and Efficacy of Upadacitinib to Dupilumab in Children From 2 to Less Than 12 Years of Age With Moderate to Severe Atopic Dermatitis
Overview
- Phase
- Phase 3
- Intervention
- Upadacitinib
- Conditions
- Atopic Dermatitis
- Sponsor
- AbbVie
- Enrollment
- 675
- Locations
- 299
- Primary Endpoint
- Percentage of Participants Achieving a 75% Reduction from Baseline in Eczema Area and Severity Index 75 (EASI 75) Score (other than US)
- Status
- Recruiting
- Last Updated
- 25 days ago
Overview
Brief 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 after the last dose of upadacitinib and at least 12 weeks after the last dose of dupilumab.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A minimum weight of 10 kg and weight and height \> 5th percentile for their age according to local standard growth charts at the Baseline Visit.
- •Atopic Dermatitis (AD), according to Hanifin and Rajka criteria, with onset of symptoms at least 6 months prior to Baseline.
- •Eczema Area and Severity Index (EASI) score \>= 16; vIGA-AD score \>= 3 (Note: In countries where dupilumab is only approved for severe AD, subjects to be included in the Randomized Cohort should have severe AD \[vIGA-AD = 4\]); \>= 10% Body Surface Area of AD involvement at the Baseline Visit; and Baseline weekly average of daily Worst Itch Scale (WIS) or Worst Scratch/Itch numerical rating scale (WSI-NRS) \>=
- •Participant must satisfy at least one of the following criteria (Note: More than 1 criterion may apply to an individual participant. All applicable criteria for each individual participant should be reported):
- •To be included in the Randomized Cohort (Note: Participants must have severe AD \[vIGA-AD = 4\] in countries where dupilumab is approved only for severe AD.):
- •\[For all countries except US\] Documented history of inadequate response or intolerance to TCS and/or TCI OR for whom use of one or more of these topical treatments is medically inadvisable (e.g., high disease burden, Scoring Atopic Dermatitis (SCORAD) \> 50, EASI score \> 21, or vIGA-AD \> 3).
- •For dupilumab-naïve participants: History of inadequate response to a systemic therapy for AD other than dupilumab or oral corticosteroids or for whom the available systemic treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
- •History of inadequate response to 2 or more courses of oral corticosteroid therapy given for \>= 14 days within 6 months prior to Screening or history of oral corticosteroid rebound, defined as recurrence of AD symptoms within 4 months after its discontinuation.
- •For dupilumab-exposed participants: Prior exposure to dupilumab without documented history of inadequate response or intolerance (i.e., discontinuation of dupilumab for a non-medical reason, such as, but not limited to, non-coverage or loss of coverage for the drug by health insurance, or other logistic challenges \[not safety- or efficacy-related\] precluding the participants continued access to dupilumab).
- •To be included in the Dupi-IR/Dupi-Medically Inadvisable Cohort:
Exclusion Criteria
- •Current or past history of other active skin diseases (e.g., psoriasis or Netherton syndrome or lupus erythematosus) or skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline Visit or which would interfere with the appropriate assessment of AD lesions.
- •Have used topical treatments for AD (except for topical emollient treatments) including but not limited to TCS, TCI, or topical phosphodiesterase type 4 (PDE-4) inhibitors, within 7 days of the Baseline Visit or any the following prohibited concomitant AD treatments within the specified timeframes below prior to the Baseline Visit:
- •Systemic therapy for AD, including but not limited to corticosteroids, methotrexate, cyclosporine, azathioprine, PDE-4 inhibitors, interferon-γ, and mycophenolate mofetil within 4 weeks;
- •Dupilumab within 8 weeks;
- •Targeted biologic treatments (other than dupilumab) within 5 half-lives (if known) or within 12 weeks, whichever is longer;
- •Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere with disease assessments within 4 weeks.
- •Known history of retinal detachment, previous cataract surgery, previous significant ocular trauma, or a known congenital ocular abnormality.
- •For Randomized Cohort: diagnosed active parasitic infection; suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization.
Arms & Interventions
Dupi-IR Cohort
Participants in this cohort will receive upadacitinib medium dose.
Intervention: Upadacitinib
Randomized Cohort
Participants in the Randomized Cohort will be randomized to receive either medium dose upadacitinib daily adult equivalent dose, low dose upadacitinib daily adult equivalent dose or dupilumab every 2 weeks or 4 weeks (at the label-indicated dose and frequency).
Intervention: Upadacitinib
Randomized Cohort
Participants in the Randomized Cohort will be randomized to receive either medium dose upadacitinib daily adult equivalent dose, low dose upadacitinib daily adult equivalent dose or dupilumab every 2 weeks or 4 weeks (at the label-indicated dose and frequency).
Intervention: Dupilumab
Outcomes
Primary Outcomes
Percentage of Participants Achieving a 75% Reduction from Baseline in Eczema Area and Severity Index 75 (EASI 75) Score (other than US)
Time Frame: At Week 16
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.
Percentage of participants achieving validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0 or 1 with a reduction from Baseline of ≥ 2 points (US and China only, descriptive)
Time Frame: Week 16
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.
Number of Participants with Adverse Events (AEs)
Time Frame: Up to Approximately Week 172
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
Secondary Outcomes
- Percentage of Participants Achieving a 75% Reduction from Baseline in EASI 75 Score (US)(At Week 16)
- Percentage of participants achieving a 50% reduction from Baseline in EASI 50 score(At Week 16)
- Percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline(At Week 16)
- Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points(At Week 160)
- 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(At Week 8)
- Percentage of participants ≥ 4 years of age with a Baseline CDLQI score of >1 achieving a CDLQI score of 0 or 1(At Week 16)
- Use of topical or systemic rescue therapy 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(At Week 16)
- Percentage of participants achieving an improved (reduced) Patient Oriented Eczema Measure (POEM) of ≥ 4 points from from participants with POEM ≥ 4 at Baseline(At 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 vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points(At Week 16)
- Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points(At Week 52)