A Phase 2/3 Study Investigating the Pharmacokinetics, Safety, and Efficacy of Dupilumab in Patients Aged ≥6 Months to <6 Years With Moderate-to-Severe Atopic Dermatitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 202
- 试验地点
- 2
- 主要终点
- Part A: Time to Reach the Maximum Serum Concentration (Tmax) of Dupilumab
研究概览
简要总结
This study is a 2-part (parts A and B) phase 2/3 study to evaluate the safety, pharmacokinetics (PK) and efficacy of dupilumab in participants 6 months to less than 6 years of age with moderate-to-severe atopic dermatitis (AD).
详细描述
- Part A (open-label, single-ascending-dose, sequential cohort phase 2 study):
- Primary objective is to characterize the safety and PK of dupilumab administered as a single dose in pediatric participants, 6 months to less than 6 years of age, with severe AD.
- Secondary objective is to evaluate the efficacy and immunogenicity of a single dose of dupilumab in participants 6 months to less than 6 years of age with severe AD.
- Part B (randomized, double-blind, parallel-group, placebo-controlled phase 3 study):
- Primary objective is to demonstrate the efficacy of multiple doses of dupilumab over 16 weeks of treatment when administered concomitantly with topical corticosteroids (TCS) in pediatric participants, 6 months to less than 6 years of age, with moderate-to-severe AD.
- Secondary objective is to assess the safety and immunogenicity of multiple doses of dupilumab over 16 weeks of treatment when administered concomitantly with TCS in participants 6 months to less than 6 years of age with moderate-to-severe AD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Part A: Open Label;
Part B: Masked, Randomized
入排标准
- 年龄范围
- 6 Months 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A (Open label Dupilumab): Age cohorts 1 & 2
Age cohort 1: ≥2 years old to <6 years old
Age cohort 2: ≥6 months to <2 years old
干预措施: Dupilumab (Drug)
Part B (Double-blind): Dupilumab dose 1
The results of part A will be used to guide the selection of dose levels and dosing frequency for part B.
干预措施: Dupilumab (Drug)
Part B (Double-blind): Dupilumab dose 2
The results of part A will be used to guide the selection of dose levels and dosing frequency for part B.
干预措施: Dupilumab (Drug)
Part B (Double-Blind): Placebo
干预措施: Matching placebo (Drug)
结局指标
主要结局
Part A: Time to Reach the Maximum Serum Concentration (Tmax) of Dupilumab
时间窗: Post-dose on Days 1, 3, 8, 18, and 29
Tmax was obtained directly from the concentration versus time curve.
Part A: Last Quantifiable Serum Concentration (Clast) of Dupilumab
时间窗: Post-dose on Days 1, 3, 8, 18, and 29
Clast is the last measurable serum concentration of dupilumab.
Part A: Time of the Last Quantifiable Serum Concentration (Tlast) of Dupilumab
时间窗: Post-dose on Days 1, 3, 8, 18, and 29
Tlast was defined as the last time point with a measurable serum concentration of dupilumab.
Part A: Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast) of Dupilumab
时间窗: Post-dose on Days 1, 3, 8, 18, and 29
AUClast was defined as area under the serum concentration time-curve from zero to the last measured concentration.
Part A: Dose Normalized Area Under the Serum Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUClast/Dose) of Dupilumab
时间窗: Post-dose on Days 1, 3, 8, 18, and 29
Dose normalized AUClast was calculated by AUClast/dose.
Part A: Maximum Observed Serum Concentration (Cmax) of Functional Dupilumab
时间窗: Post-dose on Days 1, 3, 8, 18, and 29
Serum concentration of functional dupilumab was reported.
Part A: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Dupilumab
时间窗: Post-dose on Days 1, 3, 8, 18, and 29
Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in Milligrams per Liter/Milligrams per Kilogram (\[mg/L\]/\[mg/kg\]).
Part A: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
时间窗: Baseline up to Week 4
Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may/may not have a causal relationship with study drug. Serious AE (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAE was defined as AE starting/worsening after first intake of study drug. TEAEs included participants with both SAEs and non-SAEs. Number of participants with TEAEs is reported.
Part A: Number of Participants With TEAEs by Severity According to Qualitative Toxicity Scale
时间窗: Baseline up to Week 4
Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported.
Part B: Percentage of Participants With Investigator's Global Assessment (IGA) Score 0 or 1 at Week 16
时间窗: Week 16
The IGA is an assessment scale used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 to 4 where 0 = clear; 1=almost clear; 2=mild; 3=moderate; 4=severe. A negative change from baseline indicated improvement. Percentage of participants with IGA score of '0' or '1' is reported.
Part B: Percentage of Participants With Eczema Area and Severity Index (EASI) -75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
时间窗: Week 16
The EASI score is used to measure the severity and extent of AD and measured 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 indicating the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline at Week 16.
次要结局
- Part A: Number of Participants With Serious TEAEs and Severe TEAEs(Baseline up to Week 4)
- Part A: Percent Change From Baseline in EASI Score at Week 4(Week 4)
- Part A: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 4(Week 4)
- Part A: Percentage of Participants With IGA Score 0 or 1 at Week 4(Week 4)
- Part A: Number of Participants With at Least One Positive Treatment-Emergent Anti-Drug Antibodies (ADA)(Baseline up to Day 57)
- Part B: Number of Participants With at Least One Serious Adverse Event (SAE) Through Week 16(Baseline through Week 16)
- Part B: Number of Participants With at Least One Skin Infection Treatment Emergent Adverse Event (TEAE) (Excluding Herpetic Infection) Through Week 16(Baseline through Week 16)
- Part B: Number of Participants With at Least One Positive Treatment-Emergent ADA(Baseline up to Day 197)
- Part B: Percent Change From Baseline in EASI Score at Week 16(Week 16)
- Part B: Percent Change From Baseline in Weekly Average of Daily Worst Scratch/Itch/Numerical Rating Scale (NRS) at Week 16(Week 16)
- Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥4 Points at Week 16(Week 16)
- Part B: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) at Week 16(Week 16)
- Part B: Percentage of Participants With Improvement (Reduction From Baseline) of Weekly Average of Daily Worst Scratch/Itch/NRS ≥3 Points at Week 16(Week 16)
- Part B: Change From Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16(Week 16)
- Part B: Percentage of Participants Who Achieved EASI-50 (≥50% Improvement From Baseline) at Week 16(Week 16)
- Part B: Percentage of Participants Who Achieved EASI-90 (≥90% Improvement From Baseline) at Week 16(Week 16)
- Part B: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 16(Week 16)
- Part B: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16(Week 16)
- Part B: Change From Baseline in Participant's Sleep Quality NRS at Week 16(Week 16)
- Part B: Change From Baseline in Participant's Skin Pain NRS at Week 16(Week 16)
- Part B: Change From Baseline in Dermatitis Family Index (DFI) at Week 16(Week 16)
- Part B: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16(Week 16)
- Part B: Percentage of Topical Corticosteroid (TCS) Medication-free Days From Baseline to Week 16(Baseline up to Week 16)
- Part B: Mean Weekly Dose of Low Potency TCS in Grams From Baseline to Week 16(Baseline up to Week 16)
- Part B: Mean Weekly Dose of TCS in Grams for Medium or High Potency TCS From Baseline to Week 16(Baseline up to Week 16)
- Part B: Mean Number of Caregiver Missed Work Days Through Week 16(Baseline through Week 16)