A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 912
- 试验地点
- 392
- 主要终点
- Main Study: Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16
研究概览
简要总结
The objective of this study is to assess the efficacy and safety of upadacitinib for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.
详细描述
This study includes a 35-day screening period, a 16-week double-blind period, a blinded extension period up to Week 260, and a 30-day follow-up visit.
Participants who meet eligibility criteria in the main study will be randomized in a 1:1:1 ratio to receive a daily oral dose of upadacitinib 30 mg or upadacitinib 15 mg or matching placebo. Upon completion of enrollment of a minimum of 810 participants in the main study, a supplemental study will continue to enroll adolescents (adolescent sub-study) until a total of 180 adolescent participants are enrolled overall (main study + adolescent sub-study).
Randomization in the main study will be stratified by baseline disease severity (validated Investigator Global Assessment scale for Atopic Dermatitis [vIGA-AD] score of moderate [3] versus severe [4]), by geographic region (United States [US]/Puerto Rico/Canada, and Other), and by age (adolescent [ages 12 to 17] versus adult [ages 18 to 75]). The separate randomization for the adolescent sub-study will be stratified by baseline disease severity (moderate [vIGA-AD = 3] vs. severe [vIGA-AD = 4]) and by geographic region (US/Puerto Rico/Canada and Other).
At Week 16 of the main study and the adolescent sub-study, participants in the placebo group will be re-randomized in a 1:1 ratio to receive daily oral doses of upadacitinib 30 mg or upadacitinib 15 mg in the blinded extension period. In the main study the re-randomization at Week 16 will be stratified by Week 16 50% improvement in Eczema Area and Severity Index [EASI 50] responder [Yes/No], geographic region [US/Puerto Rico/Canada, and other], and age group [adolescent/adult]. For the adolescent sub-study, the re-randomization will be stratified by EASI 50 responder (Yes/No) and by geographic region (US/Puerto Rico/Canada and Other). Participants originally randomized to upadacitinib will continue upadacitinib in the extension period at the same dose.
Starting at the Week 4 visit, rescue treatment for AD may be provided at the discretion of the investigator if medically necessary.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body weight of ≥ 40 kg at Baseline Visit for participants ≥ 12 and < 18 years of age
- •Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to Baseline and subject meets Hanifin and Rajka criteria
- •Active moderate to severe AD defined by Eczema Area and Severity Index (EASI) ≥ 16, validated Investigator's Global Assessment (vIGA) ≥ 3, body surface area (BSA) affected by AD ≥ 10%, and weekly average of daily Worst Pruritus numerical rating scale (NRS) score ≥
- •Candidate for systemic therapy or have recently required systemic therapy for AD
- •Documented history (within 6 months prior to Baseline) of inadequate response to topical corticosteroid (TCS) or topical calcineurin inhibitor (TCI) or documented systemic treatment for AD or for whom topical treatments are otherwise medically inadvisable due to side effects or safety risks
排除标准
- •Prior exposure to any Janus kinase (JAK) inhibitor
- •Unable or unwilling to discontinue current AD treatments prior to the study
- •Requirement of prohibited medications during the study
- •Other active skin diseases or skin infections requiring systemic treatment or would interfere with appropriate assessment of atopic dermatitis lesions
- •Female subject who is pregnant, breastfeeding, or considering pregnancy during the study
研究组 & 干预措施
Placebo / Upadacitinib
Participants will receive placebo orally once a day (QD) for 16 weeks in the double-blind treatment period. At Week 16, participants will be re-randomized to receive either upadacitinib 15 mg or upadacitinib 30 mg QD up to Week 260.
干预措施: Placebo for Upadacitinib (Drug)
Placebo / Upadacitinib
Participants will receive placebo orally once a day (QD) for 16 weeks in the double-blind treatment period. At Week 16, participants will be re-randomized to receive either upadacitinib 15 mg or upadacitinib 30 mg QD up to Week 260.
干预措施: Upadacitinib (Drug)
Upadacitinib 15 mg QD
Participants will receive upadacitinib 15 mg orally once a day for up to 260 weeks.
干预措施: Upadacitinib (Drug)
Upadacitinib 30 mg QD
Participants will receive upadacitinib 30 mg orally once a day for up to 260 weeks.
干预措施: Upadacitinib (Drug)
结局指标
主要结局
Main Study: Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16
时间窗: Baseline and 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.
Main Study: Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16
时间窗: Baseline and 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, no oozing or crusting; * 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.
次要结局
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (NRS) at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Main Study: Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16(Baseline and Week 16)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4(Baseline (last available rolling average before the first dose of study drug) and Week 4)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16(Baseline and Week 16)
- Main Study: Percentage of Participants Achieving an EASI 75 Response at Week 2(Baseline and Week 2)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1(Baseline (last available rolling average before the first dose of study drug) and Week 1)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2(Baseline and Day 2)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3(Baseline and Day 3)
- Main Study: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period(From first dose of study drug to Week 16)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in Atopic Dermatitis Impact Scale (ADerm-IS) Sleep Domain Score at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain Score at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS 7-Item Total Symptom Score (TSS-7) at Week 16(Baseline and Week 16)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16(Baseline and Week 16)
- Main Study: Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16(Baseline and Week 16)
- Main Study: Percent Change From Baseline in Worst Pruritus NRS at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Main Study: Percent Change From Baseline in EASI Score at Week 16(Baseline and Week 16)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Week 16(Baseline and Week 16)
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Dermatology Life Quality Index (DLQI) at Week 16(Baseline and Week 16)
- Main Study: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16(Baseline and Week 16)
- Main Study: Percentage of Participants Achieving a Hospital Anxiety and Depression Scale-Anxiety (HADS-A) Score and Hospital Anxiety and Depression Scale-Depression (HADS-D) Score of < 8 at Week 16(Week 16)
- Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 2(Baseline and Week 2)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3(Baseline and Day 3)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in DLQI Score at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving HADS-A Score and HADS-D Score of < 8 at Week 16(Week 16)
- Main Study: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16(Week 16)
- Adolescents: Percentage of Participants Achieving a vIGA-AD of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving an EASI 90 Response at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1(Baseline (last available rolling average before the first dose of study drug) and Week 1)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2(Baseline and Day 2)
- Adolescents: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period(From first dose of study drug to Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in ADerm-SS Skin Pain Score at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4(Baseline (last available rolling average before the first dose of study drug) and Week 4)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in ADerm-IS Sleep Domain Score at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Adolescents: Percent Change From Baseline in Worst Pruritus NRS at Week 16(Baseline (last available rolling average before the first dose of study drug) and Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in POEM Total Score at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16(Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS TSS-7 at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving an EASI 100 Response at Week 16(Baseline and Week 16)
- Adolescents: Percent Change From Baseline in EASI Score at Week 16(Baseline and Week 16)
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16(Baseline and Week 16)
- Adolescents: Percent Change From Baseline in SCORAD Score at Week 16(Baseline and Week 16)