A Phase 3 Multi-center Trial to Evaluate the Efficacy and Safety of Tralokinumab in Combination With Topical Corticosteroids in Children (Age 2 to <12 Years) and Infants (Age 6 Months to <2 Years) With Moderate-to-severe Atopic Dermatitis. The Trial is Randomized, Double-blind, Placebo-controlled, and Parallel-group for Children (Age 2 to <12 Years) and Open-label and Single-group for Infants (Age 6 Months to <2 Years)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- LEO Pharma
- 入组人数
- 195
- 试验地点
- 73
- 主要终点
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.
研究概览
简要总结
The purpose of this trial is to test whether treatment with tralokinumab (administered subcutaneous injections [SC]) in combination with topical corticosteroids (TCS) is safe and effective to treat moderate-to-severe atopic dermatitis (AD) in children and infants. This will be judged by a range of assessments that rate the severity and extent of atopic dermatitis and its symptoms, as well as general health status and quality of life. The trial will last for up to 4 years. There will be visits every 2 weeks for the first year and every 6 weeks thereafter. Some of the visits will be conducted by phone.
The study involves two different age groups: children aged 2 to under 12 years and infants aged 6 months to under 2 years. This trial compares tralokinumab +TCS to placebo + TCS for children with moderate-to-severe AD and evaluates tralokinumab + TCS for infants with moderate-to-severe AD. Infants will not receive placebo. All subjects will go through a screening process, which is the first part of the trial and will last up to 4 weeks. During this period, it will be checked if the child or infant meets the criteria to participate in the trial.
The children will be randomly assigned to receive tralokinumab + TCS or placebo + TCS for the initial 16 weeks, with the treatment being double-blinded. During the first 16 weeks, children will have a 2 out of 3 chance of getting tralokinumab and a 1 out of 3 chance of getting placebo. Thereafter, all subjects will receive tralokinumab + TCS. The infants will receive tralokinumab + TCS as open-label treatment for the entire treatment period, meaning that the participants will know they are receiving tralokinumab. After stopping treatment, all participants will enter a 4-week safety follow-up period.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
For subjects aged 2 to <12 years at screening, the trial is double-blind to ensure an objective evaluation of efficacy and safety of the Investigational Medicinal Product (IMP). The subject, the subject's caregiver(s), and the investigator involved in the clinical evaluation and monitoring of the subjects will not be aware of the treatment from baseline to Week 16. However, the site staff that responsible for administering tralokinumab will be aware of the treatment allocation as tralokinumab is visibly different from placebo and has a higher viscosity, requiring more pressure to depress the plunger during injections.
入排标准
- 年龄范围
- 6 Months 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6 months to <12 years at screening.
- •Body weight ≥9 kg at screening.
- •Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD.
- •History of AD for: ≥12 months for subjects aged ≥6 years at screening and ≥3 months for subjects aged 6 months to <6 years at screening.
- •Documented inadequate response to mid-strength TCS within 6 months before the screening visit.
- •AD involvement of ≥10% body surface area at screening and baseline according to component A of SCORAD.
- •An EASI score of ≥16 at screening and baseline.
- •An IGA score of ≥3 at screening and baseline.
- •A Child Worst Itch NRS average score of ≥4 (subjects aged ≥6 years at screening) or a Scratch ObsRO average score of ≥4 (subjects aged <6 years at screening) during the week prior to baseline.
排除标准
- •Treatment with the topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), topical phosphodiesterase-4 inhibitors (PDE-4), and topical Janus kinase inhibitors (JAK) within 1 week prior to baseline.
- •Treatment with bleach baths within 1 week prior to baseline.
- •Treatment with the immunomodulatory medications systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, Janus kinase inhibitors) and systemic corticosteroids (excludes inhaled, ophthalmic, or intranasal delivery) within 4 weeks prior to baseline.
- •Use of tanning beds or phototherapy within 4 weeks prior to baseline.
- •Treatment with a live (attenuated) or non-live vaccine within 30 days prior to the baseline visit.
- •Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment such as seborrheic dermatitis, active skin infection, scabies, cutaneous T cell lymphoma, or psoriasis.
- •Clinically significant active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals or antiprotozoal within 2 weeks before the baseline visit.
- •History of past or current hepatitis B or C including a positive hepatitis B or C test at screening.
研究组 & 干预措施
Tralokinumab + TCS for subjects aged 6 months to <2 years
Dose and dosing frequency for each subject will depend on the subject's body weight.
干预措施: Tralokinumab + TCS (Drug)
Placebo + TCS for subjects aged 2 to <12 years
Dose and dosing frequency for each subject will depend on the subject's body weight.
干预措施: Placebo + TCS (Drug)
Tralokinumab + TCS for subjects aged 2 to <12 years
Dose and dosing frequency for each subject will depend on the subject's body weight.
干预措施: Tralokinumab + TCS (Drug)
结局指标
主要结局
Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.
时间窗: At week 16
The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.
时间窗: At week 16
The EASI is a validated measure to assess the severity and extent of atopic dermatitis. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.
时间窗: At week 16
The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.
时间窗: At week 16
The EASI is a validated measure to assess the severity and extent of atopic dermatitis. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.
时间窗: At week 16
The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.
时间窗: At week 16
The EASI is a validated measure to assess the severity and extent of atopic dermatitis. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
次要结局
- Having at least 50% reduction in EASI score in subjects aged 6 month to <2 years at screening.(At week 16)
- Having at least 50% reduction in EASI score in subjects aged 2 to <12 years at screening.(At week 16)
- Percent change in affected BSA in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Percent change in affected BSA in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Reduction in Child Worst Itch numeric rating score (NRS) (weekly average) ≥4 for subjects aged 6 to <12 years at screening.(From baseline to Week 16)
- Reduction in Scratch Observer-Reported Outcome (ObsRO) (weekly average) ≥4 for subjects aged 2 to <6 years at screening.(From baseline to week 16)
- Change in Scratch Observer-Reported Outcome (ObsRO) (weekly average) in subjects aged 2 to <6 years at screening.(From baseline to week 16)
- Reduction in Scratch Observer-Reported Outcome (ObsRO) (weekly average) ≥4 for subjects aged 6 months to <2 years years at screening.(From baseline to week 16)
- Reduction of ≥4 in Child Worst Itch NRS (weekly average) for subjects aged 6 to <12 years at screening or Scratch ObsRO (weekly average) for subjects aged 2 to <6 years at screening.(From baseline to week 16)
- Percent change in Patient-Oriented Eczema Measure (POEM) in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Percent change in Patient-Oriented Eczema Measure (POEM) in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Change in Child Worst Itch NRS (weekly average) for subjects aged 6 to <12 years at screening.(From baseline to week 16)
- Percent change in affected body surface area (BSA) in subjects aged 6 month to <2 years at screening.(From baseline to week 52)
- Change in Scratch Observer-Reported Outcome (ObsRO) (weekly average) in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Rescue treatment use (yes/no) in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Rescue treatment use (yes/no) in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Number of TCS free days in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Number of TCS free days in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Percent change in affected body surface area (BSA) in subjects aged 2 to <12 years at screening.(From baseline to week 52)
- Percent change in Children's Dermatology Life Quality Index (CDLQI) in subjects aged 4 to <12 years at screening.(From baseline to week 52)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 16)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 16)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 6 month to <2 years at screening.(At week 16)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 16)
- Percent change in EASI in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Percent change in EASI in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Percent change in Scoring Atopic Dermatitis (SCORAD) in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Percent change in Scoring Atopic Dermatitis (SCORAD) in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Percent change in Children's Dermatology Life Quality Index (CDLQI) for subjects aged 4 to <12 years at screening.(From baseline to Week 16)
- Reduction of in Patient-Oriented Eczema Measure (POEM) ≥6 in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Reduction of in Patient-Oriented Eczema Measure (POEM) ≥6 in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Reduction in Children's Dermatology Life Quality Index (CDLQI) ≥6 for subjects aged 4 to <12 years at screening.(From baseline to week 16)
- Number of treatment-emergent adverse events (AEs) per subject aged 2 to <12 years at screening.(From baseline to week 16)
- Number of treatment-emergent adverse events (AEs) per subject aged 6 month to <2 years at screening.(From baseline to week 16)
- Presence of treatment-emergent anti-drug antibodies (yes/no) in subjects aged 2 to <12 years at screening.(From baseline to week 16)
- Presence of treatment-emergent anti-drug antibodies (yes/no) in subjects aged 6 month to <2 years at screening.(From baseline to week 16)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.(At week 52)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 52)
- Reduction in Children's Dermatology Life Quality Index (CDLQI) ≥ 6 for subjects aged 4 to <12 years at screening.(From baseline to week 100)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 6 month to <2 years at screening.(At week 52)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 52)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 52)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 52)
- Percent change in EASI in subjects aged 2 to <12 years at screening.(From baseline to week 52)
- Percent change in EASI in subjects aged 6 month to <2 years at screening.(From baseline to week 52)
- Percent change in Scoring Atopic Dermatitis (SCORAD) in subjects aged 2 to <12 years at screening.(From baseline to week 52)
- Percent change in Scoring Atopic Dermatitis (SCORAD) in subjects aged 6 month to <2 years at screening.(From baseline to week 52)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 2 to <12 years at screening.(From baseline to week 52)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 6 month to <2 years at screening.(From baseline to week 52)
- Reduction in Children's Dermatology Life Quality Index (CDLQI) ≥6 for subjects aged 4 to <12 years at screening.(From baseline to week 52)
- Reduction of in Patient-Oriented Eczema Measure (POEM) ≥6 in subjects aged 2 to <12 years at screening.(From baseline to week 52)
- Reduction of in Patient-Oriented Eczema Measure (POEM) ≥6 in subjects aged 6 month to <2 years at screening.(From baseline to week 52)
- Number of treatment-emergent adverse events (AEs) per subject aged 2 to <12 years at screening.(From week 16 to 52)
- Number of treatment-emergent adverse events (AEs) per subject aged 6 month to <2 years at screening.(From week 16 to 52)
- Presence of treatment-emergent anti-drug antibodies (yes/no) in subjects aged 2 to <12 years at screening.(From week 16 to 52)
- Presence of treatment-emergent anti-drug antibodies (yes/no) in subjects aged 6 month to <2 years at screening.(From week 16 to 52)
- Number of treatment-emergent adverse events (AEs) per subject aged 2 to <12 years at screening.(From week 52 to end of treatment)
- Number of treatment-emergent adverse events (AEs) per subject aged 6 month to <2 years at screening.(From week 52 to end of treatment)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.(At week 100)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 6 month to <2 years at screening.(At week 100)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 100)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 100)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 100)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 100)
- Percent change in EASI in subjects aged 2 to <12 years at screening.(From baseline to week 100)
- Percent change in EASI in subjects aged 6 month to <2 years at screening.(From baseline to week 100)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 2 to <12 years at screening.(From baseline to week 100)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 6 month to <2 years at screening.(From baseline to week 100)
- Percent change in Children's Dermatology Life Quality Index (CDLQI) for subjects aged 4 to <12 years at screening.(From baseline to week 100)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.(At week 148)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 6 month to <2 years at screening.(At week 148)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 148)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 148)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 148)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 148)
- Percent change in EASI in subjects aged 2 to <12 years at screening.(From baseline to week 148)
- Percent change in EASI in subjects aged 6 month to <2 years at screening.(From baseline to week 148)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 2 to <12 years at screening.(From baseline to week 148)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 6 month to <2 years at screening.(From baseline to week 148)
- Percent change in Children's Dermatology Life Quality Index (CDLQI) for subjects aged 4 to <12 years at screening.(From baseline to week 148)
- Reduction in Children's Dermatology Life Quality Index (CDLQI) ≥ 6 for subjects aged 4 to <12 years at screening.(From baseline to week 148)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 2 to <12 years at screening.(At week 196)
- Investigator's Global Assessment for atopic dermatitis (IGA 0/1) score of 0 (clear) or 1 (almost clear) in subjects aged 6 month to <2 years at screening.(At week 196)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 196)
- Having at least 75% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 196)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 2 to <12 years at screening.(At week 196)
- Having at least 90% reduction in Eczema Area and Severity Index (EASI) score in subjects aged 6 month to <2 years at screening.(At week 196)
- Percent change in EASI in subjects aged 2 to <12 years at screening.(From baseline to week 196)
- Percent change in EASI in subjects aged 6 month to <2 years at screening.(From baseline to week 196)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 2 to <12 years at screening.(From baseline to week 196)
- Percent change in Scoring Atopic Dermatitis (SCORAD) sleep loss in subjects aged 6 month to <2 years at screening.(From baseline to week 196)
- Percent change in Children's Dermatology Life Quality Index (CDLQI) for subjects aged 4 to <12 years at screening.(From baseline to week 196)
- Reduction in Children's Dermatology Life Quality Index (CDLQI) ≥ 6 for subjects aged 4 to <12 years at screening.(From baseline to week 196)