A Study to Evaluate the Dose-exposure, Safety, and Exploratory Efficacy of Nerandomilast in Children and Adolescents From 2 Years to Less Than 18 Years of Age With Fibrosing Interstitial Lung Disease (Part A: Double-blind, Placebo-controlled in Children From 6 to Less Than 18 Years of Age and Open-label Active Treatment in Children From 2 to Less Than 6 Years of Age), Followed by an Open-label Phase With Active Treatment (Part B)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 61
- 主要终点
- Area under the concentration curve (AUC) T,SS based on sampling at steady state using rich sampling in participants from 6 years to less than 18 years and sparse sampling in participants younger than 6 years
研究概览
简要总结
This study is open to children and adolescents aged 2 to 17 years with interstitial lung disease (ILD). Nerandomilast has just been approved in some countries to help adults with a lung condition called idiopathic pulmonary fibrosis. The purpose of this study is to understand how nerandomilast is tolerated and handled by the body and whether nerandomilast also helps children and adolescents with ILD.
For participants aged 6 to 17 years when joining, the study has 2 parts. In the first part, participants are put into 1 of 2 groups randomly, which means by chance. One group gets nerandomilast and the other group placebo. Placebo looks like nerandomilast but does not contain any medicine.
Participants are twice as likely to be in the nerandomilast group. They take tablets twice a day for 6 months. After these 6 months, in the second part of this study, they get nerandomilast for at least 2 years regardless of what they got in the first part.
Young participants aged 2 to 5 years when joining get nerandomilast from the start. They receive tablets twice a day for at least 2 and a half years.
Depending on when a person joins, the study lasts between 2 and a half years and up to 5 years. During this time, participants may visit the study site about 18 to 30 times. Study doctors collect blood samples to check participants' health and to find out how their body handles the study medicine. Doctors also check the function of the lungs, body growth, and how participants feel. The study doctors also regularly check participants' health and take note of any changes. For participants aged 6 to 17 years, the results are compared between the groups to see whether nerandomilast treatment helps children and adolescents.
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)
盲法说明
Masking applies to double-blind part of the trial.
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
- •Children and adolescents 2 to <18 years old at Visit
- •Participants with evidence of fibrosing ILD on high-resolution computed tomography (HRCT) within 12 months of Visit 1 as assessed by the investigator and confirmed by central review.
- •For children ≥6 years: Participants with forced vital capacity (FVC) % predicted ≥25% at Visit
- •Participants with clinically significant fibrosing ILD at Visit 2, as assessed by the investigator based on any of the following:
- •Fan score ≥3, or
- •Documented evidence of clinical progression over time based on either
- •a 5-10% relative decline in FVC % predicted accompanied by worsening symptoms, or
- •a ≥10% relative decline in FVC % predicted, or
- •increased fibrosis on HRCT, or
- •other measures of clinical worsening attributed to progressive lung disease (e.g. increased oxygen requirement, decreased diffusion capacity).
- •Further inclusion criteria apply.
排除标准
- •Previous treatment with nerandomilast.
- •Participants treated with other oral/systemic PDE4 and non-selective PDE inhibitors within 30 days before Visit
- •Participants treated with pirfenidone in the 8 weeks prior to Visit
- •Unstable pulmonary arterial hypertension (PAH).
- •Active vasculitis, unstable or uncontrolled within 8 weeks prior to Visit 1 or during the screening period.
- •Any suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour) in the past (lifetime).
- •Any suicidal ideation of type 4 or 5 on the columbia suicidal severity rating scale (C-SSRS) in the past 3 months at Visit 1 or at Visit 2 (i.e. active suicidal thought with method and intent but without specific plan; or active suicidal thought with method, intent, and plan).
- •Participants with clinically significant depression symptoms defined as the short version of mood and feeling questionnaire (SMFQ) score ≥
- •Further exclusion criteria apply.
研究组 & 干预措施
Participants aged 6 to <18 years, group 2
Part A: Placebo (blinded), Part B: Nerandomilast (open-label)
干预措施: Placebo (Drug)
Participants aged 6 to <18 years, group 1
Part A: Nerandomilast (blinded), Part B: Nerandomilast (open-label)
干预措施: Nerandomilast (Drug)
Participants aged 2 to <6 years
Part A and Part B: Nerandomilast (open-label)
干预措施: Nerandomilast (Drug)
结局指标
主要结局
Area under the concentration curve (AUC) T,SS based on sampling at steady state using rich sampling in participants from 6 years to less than 18 years and sparse sampling in participants younger than 6 years
时间窗: At week 2 in Part A and Week 28 in Part B
Occurrence of a treatment-emergent adverse event
时间窗: up to Week 26
次要结局
- Acceptability based on number/size of tablets(at Week 2 and Week 26)
- Acceptability based on the use of the dispenser(at Week 2 and Week 26)
- Absolute change from baseline in FVC [% predicted] (applicable to participants ≥6 years)(at Week 26 and Week 52)
- Absolute change from baseline in 6-min walk distance [m] (applicable to participants ≥6 years)(at Week 26 and Week 52)
- Absolute change from baseline in oxygen saturation (SpO2) [%] on room air at rest(at Week 26 and Week 52)
- Absolute change from baseline in height [cm](at Week 26 and Week 52)
- Absolute change from baseline in pediatric quality of life inventory (PedsQL™)(at Week 26 and Week 52)
- Occurrence of a treatment-emergent adverse event (Yes/No) over the whole trial(up to 5 years)
- Time to first respiratory-related hospitalisation [days] over the whole trial(up to 5 years)
- Time to first acute interstitial lung disease (ILD) exacerbation or death [days] over the whole trial(up to 5 years)
- Time to death [days] over the whole trial(up to 5 years)
- Participant acceptability based on number/size of tablets(at Week 2 and Week 26)
- Participant acceptability based on the use of the dispenser(at Week 2 and Week 26)