A Phase 3, 2-Part, Open-Label and Double-Blind, Randomised Study to Evaluate the Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis
概览
- 阶段
- 3 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Dermatitis, Atopic
- 发起方
- Almirall, S.A.
- 入组人数
- 520
- 试验地点
- 8
- 主要终点
- Part 1: Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score Less than or Equal to (<=) 7 at Week 24
- 状态
- 进行中（未招募）
- 最后更新
- 11天前
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 AD in Part 1 and to describe how similar is the current maintenance dosing regimen of lebrikizumab 250 mg every 4 weeks (Q4W) to the new proposed; lebrikizumab 500 mg every 12 weeks (Q12W), in terms of efficacy, safety, PK, ADA and blood biomarkers.
详细描述
This study consists of two parts. Part 1 is a single-arm, open-label design, where participants will receive lebrikizumab subcutaneous (SC) injections up to Week 24. Part 2 is a randomized, double-blind design, in which participants who achieve clinical response in Part 1 will continue receiving lebrikizumab treatment across two periods: a Run-in period and a Double-blind period. Participants who do not maintain at least a 50% reduction in Eczema Area and Severity Index (EASI) from baseline during Double-Blind Period will enter an Escape Arm.
研究者
入排标准
入选标准
- •Adults and adolescents (aged greater than or equal to \[\>=\] 12 to less than \[\<\] 18 at the time of informed consent form \[ICF\]/informed assent form \[IAF\] signature and weighing 40 \>= kilograms \[kg\]) who are candidates for systemic AD therapy.
- •Chronic AD (according to Hanifin and Rajka Criteria (Hanifin 1980)) 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 Day 1/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 (Sampson 2006).
- •Uncontrolled chronic disease that might require bursts of oral corticosteroids, eg, comorbid 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 before or during screening or development 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 (as defined by Winthrop et al. (Winthrop 2015))
- •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 any hepatitis virus.
研究组 & 干预措施
Part 2: Double-Blind (Placebo)
At the end of the Run-In Period, participants who demonstrate sustained clinical response will continue treatment in the double-blind period. They will either receive lebrikizumab matching placebo 250 mg SC injection (1 injection) Q4W or switch to lebrikizumab matching placebo 500 mg SC injection (2 injections) Q12W for 36 weeks.
干预措施: Placebo
Part 1: Open label (Lebrikizumab)
Participants with moderate-to-severe AD will receive loading doses of lebrikizumab 500 mg SC injection (2 injections) at Day 1 and Week 2 followed by 250 mg (1 injection) every 2 weeks (Q2W) after Week 4 to Week 16 followed by 250 mg (1 injection) every 4 weeks (Q4W) after Week 16 to Week 24.
干预措施: Lebrikizumab
Part 2: Open label Run-In Period (Lebrikizumab)
Participants who respond to lebrikizumab treatment at Week 24 of Part 1 will continue treatment in Part 2, which includes an 8-week open-label Run-In Period to confirm sustained clinical response. During this period, they will receive lebrikizumab 250 mg SC injection (1 injection) Q4W starting from the Week 24 visit of Part 1.
干预措施: Lebrikizumab
Part 2: Double-Blind (Lebrikizumab)
At the end of the Run-In Period, participants who demonstrate sustained clinical response will continue treatment in the double-blind period. They will either receive lebrikizumab 250 mg SC injection (1 injection) Q4W or switch to lebrikizumab 500 mg SC injection (2 injections) Q12W for 36 weeks.
干预措施: Lebrikizumab
Part 2: Open label Escape Arm (Lebrikizumab)
Participants who do not maintain at least a 50% reduction in EASI from baseline (EASI 50) during Double-Blind Period will enter an Escape Arm, in which participants are treated with open label lebrikizumab 250 mg SC injection Q4W. Study drug treatment will be discontinued in participants entering the Escape Arm who do not maintain an EASI 50 response.
干预措施: Lebrikizumab
结局指标
主要结局
Part 1: 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%).
Part 2: Percentage of Participants Achieving EASI 75 at Week 36
时间窗: At Week 36
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. EASI 75 is defined as 75% reduction from baseline in the EASI score.
Part 2: Percentage of Participants with an IGA Score of 0 or 1 and a Reduction >=2 Points
时间窗: From Baseline (Part 1) up to Week 36
The IGA is an instrument used to globally rate the severity of the participant's AD. It is based on a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (severe), and a score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting (minimal, palpable induration and significant induration).
次要结局
- Part 1: Time to Achieve an EASI Score <= 7(Baseline up to Week 24)
- Part 1: Percentage of Participants Achieving EASI <=5, and EASI <=3 at Week 24(At Week 24)
- Part 1: Percentage of Participants Achieving EASI 75 and EASI 90 at Week 24(At Week 24)
- Part 1: Percentage of Participants with an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction Greater Than or Equal to (>=2) Points at Week 24(At Week 24)
- Part 1: Percentage of Participants Achieving Scoring Atopic Dermatitis (SCORAD) 75, and SCORAD 90 at Week 24(At Week 24)
- Part 1: Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) at Week 24(At Week 24)
- Part 1: Percentage of Participants with Pruritus Numerical Rating Scale (NRS) >=4 at Baseline Achieving >=4-Point Improvement in Pruritus NRS(Baseline up to Week 24)
- Part 1: Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) 0-1 at Week 24(At Week 24)
- Part 1: Percentage of Participants Achieving Children Dermatology Life Quality Index (cDLQI) 0-1 at Week 24(At Week 24)
- Part 1: Percentage of Participants with DLQI >=4 at Baseline Achieving >=4-Point Improvement in DLQI(Baseline up to Week 24)
- Part 1: Percentage of Participants with cDLQI >=6 at Baseline Achieving >=6-Point Improvement in cDLQI(Baseline up to Week 24)
- Part 1: Percentage of Participants with a Sleep-Loss Scale of >=2 Points at Baseline Achieving >= 2 Point Improvement at Week 24(At Week 24)
- Part 1: Percentage of Participants with Patient-Oriented Eczema Measure (POEM) >=4 at Baseline Achieving >=4-Point Improvement in POEM(Baseline up to Week 24)
- Part 1: 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 Week 24)
- Part 2: Percentage of Participants Achieving EASI Scores <=7, and <=3 at Week 36(At Week 36)
- Part 2: Percentage of Participants Achieving EASI 90 at Week 36(At Week 36)
- Part 2: Percentage of Participants with Pruritus NRS >=4 at Baseline (Part 1) Achieving >=4-Point Improvement in Pruritus NRS at Week 36(At Week 36)
- Part 2: Percentage of Participants Achieving cDLQI 0-1 at Week 36(At Week 36)
- Part 2: Percentage of Participants with DLQI >=4 at Baseline (Part 1) Achieving >=4-Point Improvement in DLQI at Week 36(At Week 36)
- Part 2: Percentage of Participants with Pruritus NRS 0 or 1 at Week 36(At Week 36)
- Part 2: Percentage of Participants Achieving DLQI 0-1 at Week 36(At Week 36)
- Part 2: Percentage of Participants with cDLQI >=6 at Baseline (Part 1) Achieving >=6-Point Improvement in cDLQI at Week 36(At Week 36)
- Part 2: Percentage of Participants with a Sleep-Loss Scale of >=2 Points at Baseline (Part 1) Achieving >= 2 Point Improvement at Week 36(At Week 36)
- Part 2: Percentage of Participants with POEM >=4 at Baseline (Part 1) Achieving >=4-Point Improvement in POEM at Week 36(At Week 36)
- Part 2: Percentage of Participants with TEAEs, SAEs, Related AEs, AEs Leading to Study Treatment Discontinuation, and AESIs(From Week 24 up to Week 68)