A Randomised, Double-Blind, Placebo-Controlled Phase 3 Clinical Trial to Assess the Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adult and Adolescent Patients With Moderate-To-Severe Atopic Dermatitis That Are Not Adequately Controlled With Cyclosporine or For Whom Cyclosporine is Not Medically Advisable.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 331
- 试验地点
- 48
- 主要终点
- Double-blind Induction Period: Percentage of Participants Who Achieved Eczema Area and Severity Index (EASI) 75 (>=75% Reduction From Baseline in EASI Score) at Week 16
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy of lebrikizumab compared with placebo in participants not adequately controlled with cyclosporine or for whom cyclosporine is not medically advisable up to Week 16.
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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults and adolescents (aged greater than or equal to (>=) 12 to <18 years at the time of Informed Consent Form (ICF)/Informed Assent Form (IAF) and weighing >=40 kilograms).
- •Chronic AD that has been present for >=1 year before the Screening visit.
- •EASI score >=16 at the Baseline Visit.
- •IGA score >=3 (moderate) (scale of 0 [clear] to 4 [severe]) at the Baseline visit.
- •>=10% BSA of AD involvement at the Baseline visit.
- •Inadequate response to existing topical medications
- •Failure to cyclosporine or non-medically advisable to receive/continue receiving cyclosporine
- •Signed ICF (and informed assent for adolescents as required)
排除标准
- •Treatment with TCS within 1 week before the Baseline visit.
- •Treatment with topical calcineurin inhibitors, phosphodiesterase-4 inhibitors such as crisaborole, or cannabinoids within 2 week before the Baseline visit.
- •Treatment with interleukin 4 (IL-4) or interleukin 13 (IL-13) antagonists biological therapies before the Baseline visit. Exception: previous treatment with dupilumab will be allowed in a subset of patients
- •Treatment with immunosuppressive/immunomodulating drugs, phototherapy and photochemotherapy within 4 weeks before the Baseline visit
- •Uncontrolled chronic disease that might require bursts of oral corticosteroids
- •Serious, opportunistic, chronic or recurring infections within 3 months of Screening or before randomization
- •Current or chronic infection with hepatitis B virus, current infection with hepatitis C virus, known liver cirrhosis and/or chronic hepatitis of any etiology
- •Known or suspected history of immunosuppression, history of HIV infection or positive HIV serology at Screening
- •Any clinically significant laboratory test results obtained at the Screening visit
- •Presence of skin comorbidities that may interfere with study assessments
- •Have had an important side effect to TCS that would prevent further use.
研究组 & 干预措施
Lebrikizumab
Lebrikizumab administered subcutaneously (SC), participants will receive 2 injections of lebrikizumab 250 mg at Baseline and Week 2, followed by 1 injection of lebrikizumab 250 milligram (mg) once every two weeks (Q2W) in the induction period up to week 16. Participants who received lebrikizumab 250 mg Q2W during the Induction Period will continue to receive lebrikizumab 250 mg Q2W during the Maintenance Period. In order to maintain the double blind, participants from the lebrikizumab 250 mg Q2W arm will be administered a second injection of blinded placebo during Week 16 and Week 18. From Week 20 up to Week 52, all participants will receive 1 injection of lebrikizumab 250 mg Q2W in Open-label maintenance period.
干预措施: Lebrikizumab (Biological)
Lebrikizumab-matching Placebo
Lebrikizumab-matching Placebo administered SC, 250 mg dose, Q2W in the induction period for 16 weeks. Participants will receive 2 injections of lebrikizumab 250 mg at Week 16 and Week 18 followed by 1 injection of lebrikizumab 250 mg Q2W from Week 20 up to Week 52 in Open-label maintenance period.
干预措施: Lebrikizumab-matching Placebo (Drug)
结局指标
主要结局
Double-blind Induction Period: Percentage of Participants Who Achieved Eczema Area and Severity Index (EASI) 75 (>=75% Reduction From Baseline in EASI Score) at Week 16
时间窗: At Week 16
The EASI score is used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. The severity of the clinical signs of AD for each of 4 body regions was scored on a 4-point scale: 0=absent, 1=mild, 2=moderate and 3=severe. The area of AD involvement on each of the 4 anatomic regions was assessed as a percentage by body area: 0=no eruption, 1=1% to 9%, 2=10% to 29%, 3=30% to 49%, 4=50% to 60%, 5=70% to 80% and 6=90% to 100%. The composite index with total score ranged from 0 to 72, where higher scores indicates more severe and or extensive disease.
次要结局
- Double-blind Induction Period: Percentage of Participants Who Achieved Investigator Global Assessment (IGA) Score of 0 or 1 and 2-point Improvement at Week 16(At Week 16)
- Double-blind Induction Period: Percentage of Participants Who Achieved a 4-point Improvement in Pruritus Numeric Rating Score (NRS) at Week 16(At Week 16)
- Double-blind Induction Period: Percentage of Participants Who Achieved EASI 75 (>=75% Reduction From Baseline in EASI Score) at Weeks 2, 4, 8, and 12(At Weeks 2, 4, 8, and12)
- Double-blind Induction Period: Percentage of Participants Who Achieved EASI 90 (>=90% Reduction From Baseline in EASI Score) at Weeks 2, 4, 8, 12 and 16(At Weeks 2, 4, 8, 12 and 16)
- Double-blind Induction Period: Percentage of Participants Who Achieved EASI 50 (>=50% Reduction From Baseline in EASI Score) at Weeks 2, 4, 8, 12 and 16(At Weeks 2, 4, 8, 12 and 16)
- Double-blind Induction Period: Percentage of Participants Who Achieved a 4-point Improvement in Dermatology Life Quality Index (DLQI) at Weeks 2, 4, 8, 12 and 16(At Weeks 2, 4, 8, 12 and 16)
- Double-blind Induction Period: Percentage of Participants Who Achieved a 4-point Improvement in Children's Dermatology Life Quality Index (CDLQI) at Weeks 2, 4, 8, 12 and 16(At Weeks 2, 4, 8, 12 and 16)
- Double-blind Induction Period: Percentage of Participants Who Achieved a 4- Point Improvement in Skin Pain NRS at Week 16(At Week 16)
- Double-blind Induction Period: Change From Baseline in Body Surface Area (BSA) at Weeks 2, 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Double-blind Induction Period: Change From Baseline in Scoring Atopic Dermatitis (SCORAD) at Weeks 8 and 16(Baseline, Weeks 8 and 16)
- Double-blind Induction Period: Change From Baseline in Pruritus NRS by Week up to Week 16(Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16)
- Double-blind Induction Period: Change From Baseline in the Sleep Loss at Week 16 Using Patient-related Outcome (PRO) by Week up to Week 16(Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16)
- Double-blind Induction Period: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at Weeks 4, 8, 12 and 16(Baseline, Weeks 4, 8, 12 and 16)
- Double-blind Induction Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 2. 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Double-blind Induction Period: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 2. 4, 8, 12 and 16(Baseline, Weeks 2, 4, 8, 12 and 16)
- Double-blind Induction Period: Change From Baseline in Skin Pain NRS by Week up to Week 16(Baseline, Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16)
- Double-blind Induction Period: Median Time (Days) to TCS-Free Use(Baseline up to Week 16)
- Double-blind Induction Period: Proportion of Topical Corticosteroids (TCS) Medication Free Days(Baseline up to Week 16)