A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Dupilumab Monotherapy in Patients ≥12 to <18 Years of Age, With Moderate-to-severe Atopic Dermatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 251
- 试验地点
- 2
- 主要终点
- Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16
研究概览
简要总结
The primary objective of the study was to demonstrate the efficacy of dupilumab as a monotherapy in participants ≥12 years to <18 years of age with moderate-to-severe atopic dermatitis (AD). The secondary objective of the study was to assess the safety of dupilumab as a monotherapy in participants ≥12 years to <18 years of age with moderate-to-severe AD.
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 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥12 to <18 years of age at time of screening visit
- •Diagnosis of AD according to the American Academy of Dermatology consensus criteria at screening visit
- •IGA ≥3 at screening and baseline visit
- •EASI ≥16 at the screening and baseline visit
- •Baseline Pruritus NRS average score for maximum itch intensity ≥4
- •≥10% BSA of AD involvement at the screening and baseline visits
- •With documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments is medically inadvisable
排除标准
- •Participation in a prior dupilumab clinical study
- •Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 2 weeks before the baseline visit
- •Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit
- •Body weight <30 kg at baseline
- •Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit
- •Known or suspected immunodeficiency, known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit, established diagnosis of HBV infection or HBV seropositivity at screening, established diagnosis of HCV infection or HCV seropositivity at screening
- •History of malignancy before the baseline visit
- •Diagnosed active endoparasitic infections or at high risk of these infections
- •Patient is female who is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
- •Patient is female of childbearing potential and sexually active, who is unwilling to use adequate methods of contraception throughout the duration of the study and for 120 days after the last dose of study drug
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Placebo
Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). In order to maintain blinding for the study, participants in the <60 kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) dupilumab (including doubling the amount of placebo on day 1 to match the loading dose) or placebo matching 300 milligram (mg) dupilumab (including doubling the amount of placebo on day 1 to match the loading dose). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab (including doubling the amount of placebo on day 1 to match the loading dose).
干预措施: Placebo (Drug)
Dupilumab 300 mg Q4W
Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. In order to maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 milliliter (mL) injection at the weeks dupilumab was not given.
干预措施: Dupilumab (Drug)
Dupilumab 200 mg or 300 mg Q2W
Participants with baseline weight <60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1.
干预措施: Dupilumab (Drug)
结局指标
主要结局
Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16
时间窗: Baseline and Week 16
IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\]
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16
时间窗: Baseline and Week 16
The EASI score was used to measure the severity and extent of AD and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI--75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered nonresponder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\]
次要结局
- Percent Change From Baseline in EASI Score at Week 16(Baseline and Week 16)
- Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4(Baseline and Week 4)
- Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at Week 16(Baseline and Week 16)
- Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16(Baseline and Week 16)
- Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16(Baseline to Week 16)
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16(Baseline to Week 16)
- Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at Week 16(Baeline and Week 16)
- Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline(Baseline up to week 16)
- Change From Baseline in Percent Body Surface Area (BSA) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16(Baseline and Week 16)
- Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16(Baseline and Week 16)
- Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline(Baseline up to Week 16)
- Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16(Baseline and Week 16)
- Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4(Baseline and Week 4)
- Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16(Baseline through Week 16)
- Percentage of Participants With Serious TEAEs Through Week 16(Baseline through Week 16)