A Phase 3b, Open-label Study to Evaluate the Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 260
- 试验地点
- 35
- 主要终点
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score Less Than or Equal to (<=) 7 at Week 24
研究概览
简要总结
The main purpose of this study is to evaluate the effectiveness of 24 weeks of lebrikizumab in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe atopic dermatitis (AD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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 >=12 to less than [<] 18 years at the time of informed consent form (ICF)/informed assent form (IAF) signature and weighing >=40 kg) who are candidates for systemic AD therapy.
- •Chronic AD that has been present for >=1 year before the Screening visit.
- •EASI score >=12 at the Day 1/Baseline Visit.
- •IGA score >=3 (moderate) (scale of 0 [clear] to 4 [severe]) at the Baseline visit.
- •>=10% BSA of AD involvement at the Day 1/Baseline visit.
- •History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
- •Completed electronic diary (eDiary) entries for pruritus and sleep-loss for a minimum of 4 of 7 days before Day 1/Baseline.
- •Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
- •For women of childbearing potential: agree to remain abstinent (refrain from heterosexual intercourse) or to use a highly effective contraceptive method during the treatment period and for at least 4 weeks or 1 menstrual period after the last dose of lebrikizumab.
- •Participant must provide signed ICF. Adolescent participants must also provide separate informed assent to enroll in the study and sign and date either a separate IAF or the ICF signed by the parent/legal guardian (as appropriate based on local regulations and requirements).
排除标准
- •Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor.
- •Intention to use any concomitant medication or therapy that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication.
- •History of anaphylaxis as defined by the Sampson criteria.
- •Uncontrolled chronic disease that might require bursts of oral corticosteroids, example, co-morbid severe uncontrolled asthma (defined by an Asthma Control Questionnaire-5 score >=1.5 or a history of >=2 asthma exacerbations within the last 12 months requiring systemic [oral and/or parenteral] corticosteroid treatment or hospitalisation for >24 hours).
- •Occurrence of the following types of infection within 3 months of Screening or develop any of these infections before Day 1/Baseline:
- •Serious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment, as per the Investigator's opinion);
- •Opportunistic
- •Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer);
- •Recurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis).
- •Known current or chronic infection with hepatitis B virus.
- •Known liver cirrhosis and/or chronic hepatitis of any aetiology.
- •Known active endoparasitic infections or at high risk of these infections.
- •Known or suspected history of immunosuppression, including history of invasive opportunistic infections (example, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator's judgement.
- •History of human immunodeficiency virus (HIV) infection or known positive HIV serology.
- •Any clinically significant laboratory test results from the chemistry or haematology tests obtained at the Screening visit that would jeopardise the patient's participation in the study, per the Investigator's judgement.
- •Presence of skin comorbidities that may interfere with study assessments.
- •History of malignancy, including mycosis fungoides, within 5 years before the Screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin with no evidence of recurrence in the past 12 weeks.
- •Severe concomitant illness(es) that in the Investigator's judgement would adversely affect the participation in the study. Any other medical or psychological condition that in the opinion of the Investigator may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study participant because of his/her participation in this clinical trial, may make participation unreliable, or may interfere with study assessments.
- •Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
研究组 & 干预措施
Lebrikizumab
Participants will receive loading doses of lebrikizumab 500 milligrams (mg) subcutaneous (SC) injection at Day 1 and Week 2 followed by lebrikizumab 250 mg SC injection, every two weeks (Q2W) from Week 4 to Week 16. At Week 16, the dosing frequency will be reduced to every 4 weeks (Q4W) and will receive lebrikizumab 250 mg SC injection for up to Week 24, last dose of study medication is administered at Week 20.
干预措施: Lebrikizumab (Biological)
结局指标
主要结局
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score Less Than or Equal to (<=) 7 at Week 24
时间窗: At Week 24
The EASI is used to assess the severity and extent of AD; it is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and or extensive disease. The severity of erythema, induration/papulation, excoriation, and lichenification will be assessed by the Investigator or trained designee on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. In addition, the extent of AD involvement in each of the 4 body areas will be assessed as a percentage by body area of head/neck, trunk, upper limbs, and lower limbs, and converted to a score of 0 (0%), 1 (0 to 9%), 2 (10 to 29%), 3 (30 to 49%), 4 (50 to 69%), 5 (70 to 89%) and 6 (90 to 100%).
Percentage of Participants Who Achieved Eczema Area and Severity Index (EASI) Total Score Less Than or Equal to (<=) 7 at Week 24
时间窗: At Week 24
The EASI is used to assess the severity and extent of AD; it is a composite index with total score ranging from 0 to 72, with higher values indicating more severe and extensive disease. The severity of erythema, induration/papulation, excoriation, and lichenification will be assessed by the Investigator or trained designee on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. In addition, the extent of AD involvement in each of the 4 body areas will be assessed as a percentage by body area of head/neck, trunk, upper limbs, and lower limbs, and converted to a score of 0 (0%), 1 (0 to 9%), 2 (10 to 29%), 3 (30 to 49%), 4 (50 to 69%), 5 (70 to 89%) and 6 (90 to 100%). Percentage of participants who achieved EASI total \<= 7 at Week 24 was reported.
次要结局
- Percentage of Participants Achieving EASI Score <=7, EASI <=5, and EASI <=3(Baseline up to Week 24)
- Percentage of Participants Achieving EASI 75 and EASI 90(Baseline up to Week 24)
- Percentage of Participants with an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction Greater Than or Equal to (>=2) Points(Baseline up to Week 24)
- Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) 75 and SCORAD 90(Baseline up to Week 24)
- Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS)(Baseline up to Week 24)
- Percentage of Participants With Pruritus Numerical Rating Scale (NRS) >=4 at Baseline Achieving >=4-Point Improvement in Pruritus NRS(Baseline up to Week 24)
- Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) 0-1(Baseline up to Week 24)
- Percentage of Participants With DLQI >=4 at Baseline Achieving >=4-Point Improvement in DLQI(Baseline up to Week 24)
- Percentage of Participants Achieving Children Dermatology Life Quality Index (cDLQI) 0-1(Baseline up to Week 24)
- Percentage of Participants With cDLQI >=6 at Baseline Achieving >=6-Point Improvement in cDLQI(Baseline up to Week 24)
- Percentage of Participants With a Sleep-Loss Scale of >=2 Points at Baseline Who Achieve at least 2-point Reduction Using PRO(Baseline up to Week 24)
- Percentage of Participants With Patient-Oriented Eczema Measure (POEM) >=4 at Baseline Achieving >=4-Point Improvement in POEM(Baseline up to Week 24)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, AEs Leading to Study Treatment Discontinuation, and Adverse Events of Special Interest (AESIs)(Baseline up to follow-up (Week 28))
- Percentage of Participants Who Achieved EASI Total Score <=7, EASI <=5, and EASI <=3 by Visit(At Weeks 2, 4, 16, and 24)
- Percentage of Participants Who Achieved EASI 75 and EASI 90 by Visit(At Weeks 2, 4, 16 and 24)
- Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction Greater Than or Equal to (>=2) Points From Baseline by Visit(At Weeks 2, 4, 16 and 24)
- Percentage of Participants Who Achieved Scoring Atopic Dermatitis (SCORAD) 75 and SCORAD 90 by Visit(At Week 2, 4, 16 and 24)
- Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) (Hands) From Baseline by Visit(Baseline, Week 2, 4, 16, and 24)
- Percentage of Participants With Pruritus Numerical Rating Scale (NRS) >=4 at Baseline Who Achieved >=4-Point Improvement in Pruritus NRS From Baseline by Visit(At Weeks 2, 4, 16 and 24)
- Percentage of Participants Who Achieved Dermatology Life Quality Index (DLQI) 0-1 by Visit(At Weeks 2, 4, 16 and 24)
- Percentage of Participants With DLQI >=4 at Baseline Who Achieved >=4-Point Improvement in DLQI From Baseline by Visit(At Weeks 2, 4, 16 and 24)
- Percentage of Participants Who Achieved Children Dermatology Life Quality Index (cDLQI) 0-1 by Visit(At Weeks 2, 4, 16 and 24)
- Percentage of Participants With cDLQI >=6 at Baseline Who Achieved >=6-Point Improvement in cDLQI From Baseline by Visit(At Week 2, 4, 16 and 24)
- Percentage of Participants With a Sleep-Loss Scale of >=2 Points at Baseline Who Achieved at Least 2-point Reduction From Baseline by Visit(At Weeks 2, 4, 16 and 24)
- Percentage of Participants With Patient-Oriented Eczema Measure (POEM) >=4 at Baseline Who Achieved >=4-Point Improvement in POEM From Baseline by Visit(At Weeks 2, 4, 16 and 24)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related TEAEs, TEAEs Leading to Study Treatment Discontinuation, and Treatment-emergent Adverse Events of Special Interest (TEAESIs)(Baseline up to follow-up (Week 28))