A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Outpatient Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Baricitinib in Pediatric Patients With Moderate to Severe Atopic Dermatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 516
- 试验地点
- 137
- 主要终点
- Open Label Pop PK: Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of LY3009104
研究概览
简要总结
The reason for this study is to see if the study drug called baricitinib works and is safe in children and teenage participants with atopic dermatitis.
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
- Double (Participant, Investigator)
盲法说明
Participants were randomized to one of the four double-blind treatment arms. A separate group of 33 participants received open label baricitinib as part of pharmacokinetic (PK) lead-in (not randomized) period.
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At or above the 5th percentile of weight for age.
- •Have been diagnosed with moderate to severe atopic dermatitis for at least 12 months (if 6 years old or older) or at least 6 months (if 2 up to 6 years old).
- •Have had inadequate response or intolerance to existing topical (applied to the skin) medications within 6 months preceding screening.
- •Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period).
- •Agree to use emollients daily.
排除标准
- •Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus), or a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections.
- •A history of eczema herpeticum within 12 months, and/or a history of 2 or more episode of eczema herpeticum in the past.
- •Participants who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics.
- •Have any serious illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).
- •Have been treated with the following therapies:
- •Monoclonal antibody for less than 5 half-lives prior to beginning study treatment.
- •Received prior treatment with any oral Janus kinase (JAK) inhibitor.
- •Received any parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned initiation of study drug or are anticipated to require parenteral injection of corticosteroids during the study.
- •Have had an intra-articular corticosteroid injection within 2 weeks prior to study entry or within 6 weeks prior to planned initiation of study drug.
- •Have high blood pressure characterized by a repeated systolic or diastolic blood pressure >95th percentile based on age, sex and height.
- •Have had major surgery within the past eight weeks or are planning major surgery during the study.
- •Have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
- •Have a history of VTE or are considered at high risk of VTE as deemed by the investigator.
- •Have a history or presence of cardiovascular, respiratory, hepatic, chronic liver disease gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness.
- •Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster (shingles or chicken pox), tuberculosis.
- •Have specific laboratory abnormalities.
- •Have received certain treatments that are contraindicated.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Baricitinib Low Dose
Participants 10 to < 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
干预措施: Baricitinib (Drug)
Baricitinib High Dose
Participants 10 to < 18 years received Baricitinib high dose (4 mg) and placebo to maintain the blind, administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib high dose (2 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
干预措施: Baricitinib (Drug)
Baricitinib Open Label High Dose (PK Lead-in)
Participants 10 to < 18 years received Baricitinib high dose (4 mg) administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib high dose (2 mg) administered as oral suspension (1 mL) QD.
干预措施: Baricitinib (Drug)
Baricitinib Medium Dose
Participants 10 to < 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
干预措施: Topical corticosteroid (Drug)
Baricitinib Low Dose
Participants 10 to < 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
干预措施: Topical corticosteroid (Drug)
Placebo
Participants 10 to < 18 years received placebo tablets. Participants 2 to < 10 years received placebo as oral suspension.
干预措施: Topical corticosteroid (Drug)
Baricitinib High Dose
Participants 10 to < 18 years received Baricitinib high dose (4 mg) and placebo to maintain the blind, administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib high dose (2 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
干预措施: Topical corticosteroid (Drug)
Baricitinib Open Label High Dose (PK Lead-in)
Participants 10 to < 18 years received Baricitinib high dose (4 mg) administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib high dose (2 mg) administered as oral suspension (1 mL) QD.
干预措施: Topical corticosteroid (Drug)
Placebo
Participants 10 to < 18 years received placebo tablets. Participants 2 to < 10 years received placebo as oral suspension.
干预措施: Placebo (Drug)
Baricitinib Medium Dose
Participants 10 to < 18 years received Baricitinib low dose (1 mg) and placebo to maintain the blind, administered orally in tablet form QD.
Participants 2 to < 10 years received Baricitinib low dose (0.5 mg) administered as oral suspension QD or placebo oral suspension QD to maintain the blind.
干预措施: Baricitinib (Drug)
结局指标
主要结局
Open Label Pop PK: Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of LY3009104
时间窗: Predose; 0.25 h; 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose
Open label Pop PK: AUCtau,ss was derived by a population pharmacokinetics approach.
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥2 Point Improvement
时间窗: Week 16
Percentage of participants achieving IGA of 0 or 1 with a ≥2 point improvement is presented. The IGA measures the investigator's global assessment of the participant's overall severity of their Atopic Dermatitis, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Open Label Population Pharmacokinetics (Pop PK): Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY3009104
时间窗: Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose
Open label Pop PK: Cmax,ss was derived by a population pharmacokinetics approach.
次要结局
- Percentage of Participants Achieving IGA of 0(Week 16)
- Change From Baseline in Itch NRS for Participants 10 to <18 Years at Study Entry(Baseline, Week 16)
- Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) for Participants 10 to <18 Years Old at Study Entry(Week 16)
- Percentage of Participants Achieving EASI50(Week 16)
- Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment(Week 16)
- Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)(Week 16)
- Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)(Week 16)
- Change From Baseline in SCORAD(Baseline, Week 16)
- Change From Baseline in Body Surface Area (BSA) Affected(Baseline, Week 16)
- Percentage of Participants Achieving EASI90(Week 16)
- Mean Number of Days Without Use of Background Topical Corticosteroid (TCS)(Baseline Through 16 Weeks)
- Change From Baseline in EASI Score(Baseline, Week 16)
- Percentage of Participants Achieving SCORAD90(Week 16)
- Change From Baseline on the Patient-Oriented Eczema Measure (POEM) Total Score(Baseline, Week 16)
- Change From Baseline in the PROMIS-Pediatric Anxiety for Participants 5 to <18 Years at Study Entry(Baseline, Week 16)
- Change From Baseline in Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score for Participants 10 to <18 Years at Study Entry(Baseline, Week 16)
- Pop PK: Area Under the Concentration-Time Curve for Dosing Interval at Steady State (AUCtau,ss) of LY3009104(Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose)
- Mean Gram Quantity of TCS Use (Tube Weights)(Baseline through 16 Weeks)
- Change From Baseline in the Parent-Reported Itch Severity Measure (PRISM) for Participants 2 to <10 Years at Study Entry(Baseline, Week 16)
- Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) at Week 16 for Participants 4 to <18 Years at Study Entry(Baseline, Week 16)
- Change of Immunoglobulin G (IgG) Titers(Baseline Through End of Study Completion)
- Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Pediatric Depression for Participants 5 to <18 Years at Study Entry(Baseline, Week 16)
- Change From Baseline in Infants' Dermatology Quality of Life Index (IDQOL) at Week 16 for Participants 2 to <4 Years at Study Entry(Week 16)
- Change From Baseline on the European Quality of Life-5 Dimensions-Youth (EQ-5D-Y) for Participants 4 to <18 Years at Study Entry(Baseline, Week 16)
- Change From Baseline in Skin Pain NRS for Participants 10 to <18 Years at Study Entry(Baseline, Week 16)
- Number of Participant Responses With Tablet Acceptability and Palatability Assessment (PK Lead-In) for Participants >=10 Years Old at Study Entry(Week 2)
- Pop PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) of LY3009104(Predose; 0.25 hours (h); 0.5 h; 1 h; 2-4 h; 4 h and 4-6 h post dose)
- Change From Baseline on the Work Productivity and Activity Impairment: Atopic Dermatitis - Caregiver (WPAI-AD-CG) Score(Baseline, Week 16)
- Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) for Participants 10 to <18 Years at Study Entry(Baseline, Week 16)
- Number of Participant Responses With Suspension Acceptability and Palatability Assessment (PK Lead-In) for Participants <10 Years Old at Study Entry(Week 2)
- Height, Weight and Body Mass Index (BMI) Growth Rate(124 Weeks)