A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of BI 1015550 Over at Least 52 Weeks in Patients With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,178
- 试验地点
- 786
- 主要终点
- Absolute Change From Baseline in Forced Vital Capacity (FVC) in Milliliters [mL] at Week 52
研究概览
简要总结
This study is open to adults with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs). People who have a form of PF-ILD other than Idiopathic Pulmonary Fibrosis (IPF) can join the study. If they already take nintedanib, they can continue treatment throughout the study.
The purpose of this study is to find out whether a medicine called BI 1015550 helps people with PF-ILD. Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of BI 1015550 as tablets twice a day. Participants in the placebo group take placebo tablets twice a day. Placebo tablets look like BI 1015550 tablets but do not contain any medicine.
Participants are in the study for up to two and a half years. During the first year, they visit the study site 10 times. Afterwards, they visit the study site every 3 months. The doctors regularly test participants' lung function. The results of the lung function tests are compared between the groups. The doctors also regularly check participants' health and take note of any unwanted effects.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥18 years old at the time of signed informed consent.
- •Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
- •Diagnosis of progressive fibrosing ILD other than IPF (physician confirmed).
- •Patients may be either:
- •on a stable therapy* with nintedanib for at least 12 weeks prior to Visit 1 and during screening and are planning to stay on this background treatment after randomization. (*stable therapy is defined as a tolerated regimen of nintedanib (with no dose changes) for at least 12 weeks)
- •not on treatment with nintedanib for at least 8 weeks prior to Visit 1 and during the screening period (e.g. either Antifibrotic (AF)-treatment naïve or previously discontinued) and do not plan to start or re-start antifibrotic treatment.
- •Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit
- •DLCO ≥25% of predicted normal corrected for hemoglobin (Hb) at Visit
- •Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control. WOCBP taking oral contraceptives (OCs) also have to use one barrier method
- •Patients treated with permitted immunosuppressive agents (other than corticosteroids) for an underlying systemic disease (e.g. Methotrexate (MTX), Azathioprine (AZA)) need to be on a stable treatment for at least 12 weeks prior to Visit 1 and during the screening period.
排除标准
- •Prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced vital capacity (FVC) <0.7 at Visit 1
- •In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
- •Acute Interstitial Lung Disease (ILD) exacerbation within 3 months prior to Visit 1 and/or during the screening period (investigator-determined).
- •Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis.
- •Patients having developed ILD due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 (COVID-19) within 12 months of screening (based on investigators judgement).
- •Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement. Registration on lung transplantation list would not be considered as planned major surgery.
- •Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
- •Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) >2.5 x upper limit of normal (ULN) or total Bilirubin >1.5 x ULN at Visit
- •Further exclusion criteria apply.
研究组 & 干预措施
Nerandomilast 9 mg
Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
干预措施: BI 1015550 (Drug)
Nerandomilast 18 mg
Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
干预措施: BI 1015550 (Drug)
Placebo
Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.
干预措施: Placebo (Drug)
结局指标
主要结局
Absolute Change From Baseline in Forced Vital Capacity (FVC) in Milliliters [mL] at Week 52
时间窗: The MMRM model is a longitudinal analysis, and it incorporated FVC measurements change from baseline at Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. Data presented is the FVC adjusted change from baseline at Week 52.
The absolute change from baseline in forced vital capacity (FVC) in milliliters \[mL\] at Week 52 is reported. The absolute change from baseline in FVC was analyzed by a restricted maximum likelihood (REML)-based mixed model with repeated measurements (MMRM) comparing the change from baseline in FVC at Week 52 between treatment groups. The analysis included the fixed, categorical effects of treatment, baseline intake of antifibrotic (AF) treatment, and baseline High-resolution Computed Tomography (HRCT) pattern at each visit, as well as the fixed continuous effects of baseline FVC value at each visit. Visits were treated as a repeated measure with an unstructured covariance structure used to model within-patient measurements.
次要结局
- Key Secondary Endpoint: Time to First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute ILD Exacerbation, First Hospitalisation for Respiratory Cause, or Death (Whichever Occurred First) Over the Duration of the Trial(From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.)
- Time to First Acute ILD Exacerbation or Death Over the Duration of the Trial(From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.)
- Time to Hospitalisation for Respiratory Cause or Death Over the Duration of the Trial(From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.)
- Time to Death Over the Duration of the Trial(From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.)
- Absolute Change From Baseline in Forced Vital Capacity (FVC) Percent (%) Predicted at Week 52(The MMRM model is a longitudinal analysis, and it incorporated FVC % predicted change from baseline at Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. Data presented is change from baseline in FVC % predicted at Week 52.)
- Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial(From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.)
- Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) % Predicted (Corrected for Hb) at Week 52(The MMRM model is a longitudinal analysis and it incorporated DLCO measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.)
- Time to Absolute Decline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Percentage Predicted by More Than 15% From Baseline or Death, Measured Over the Duration of the Trial(From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.)
- Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52(The MMRM model is a longitudinal analysis and it incorporated L-PF measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, Week 36, Week 44 and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.)
- Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52(The MMRM model is a longitudinal analysis and it incorporated L-PF measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, Week 36, Week 44 and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.)
- Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52(The MMRM model is a longitudinal analysis and it incorporated L-PF measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, Week 36, Week 44 and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.)