A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib Over 52 Weeks in Chinese Patients With Chronic Fibrosing ILDs With a Progressive Phenotype
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 16
- 主要终点
- Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks Expressed in Milliliter (mL)
研究概览
简要总结
This study in China is open to people with progressive lung fibrosis (chronic fibrosing ILDs with progressive phenotype) who are at least 18 years old. The purpose of this study is to find out whether a medicine called nintedanib helps people with progressive lung fibrosis.
Participants are put into 2 groups randomly, which means by chance. 1 group gets nintedanib as capsules twice a day. The other group gets placebo as capsules twice a day. Placebo capsules look like nintedanib capsules but do not contain any medicine.
Participants are in the study for about 1 year. During this time, they visit the study site about 10 times. At some visits, participants perform a lung function test. The doctors check whether study treatment can slow down the loss of lung function. 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
- •Written Informed Consent consistent with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study (and prior to any study procedure including shipment of High-Resolution Computed Tomography (HRCT) to reviewer.
- •Male or female patients aged ≥ 18 years at Visit
- •Patients with physician diagnosed Interstitial Lung Disease (ILD) who fulfil at least one of the following criteria for Progressive Phenotype within 24 months of screening visit (Visit 1) despite treatment with unapproved medications used in clinical practice to treat ILD, as assessed by the investigator:
- •Clinically significant decline in Forced Vital Capacity (FVC) % predicted based on a relative decline of ≥10%
- •Marginal decline in FVC % predicted based on a relative decline of ≥5-<10% combined with worsening of respiratory symptoms
- •Marginal decline in FVC % predicted based on a relative decline of ≥5-<10% combined with increasing extent of fibrotic changes on chest imaging
- •Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging [Note: Changes attributable to comorbidities e.g. infection, heart failure must be excluded. Unapproved medications used in the clinical practice to treat ILD include but are not limited to corticosteroid, azathioprine, mycophenolate mofetil (MMF), n-Acetylcysteine (NAC), rituximab, cyclophosphamide, cyclosporine, tacrolimus].
- •Fibrosing lung disease on HRCT, defined as reticular abnormality with traction bronchiectasis with or without honeycombing, with disease extent of >10%, performed within 12 months of Visit 1 as confirmed by central readers.
- •For patients with underlying Connective Tissue Disease (CTD): stable CTD as defined by no initiation of new therapy or withdrawal of therapy for CTD within 6 weeks prior to Visit
- •FVC ≥ 45% predicted at Visit 2.
排除标准
- •Aspartate Aminotransferase (AST) and / or Alanine Aminotransferase (ALT) > 1.5 x Upper Level of Normal (ULN) at Visit 1
- •Bilirubin > 1.5 x ULN at Visit 1
- •Creatinine clearance <30 milliliter (mL)/minute (min) calculated by Cockcroft-Gault formula at Visit
- •[Note: Laboratory parameters from Visit 1 have to satisfy the laboratory threshold values as shown above. Visit 2 laboratory results will be available only after randomization. In case at Visit 2 the results do no longer satisfy the entry criteria, the Investigator has to decide whether it is justified that the patient remains on study drug. The justification for decision needs to be documented. Laboratory parameters that are found to be abnormal at Visit 1 are allowed to be re-tested (once) if it is thought to be a measurement error (i.e. there was no abnormal result of this test in the recent history of the patient and there is no related clinical sign) or the result of a temporary and reversible medical condition, once that condition is resolved].
- •Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment).
- •Previous treatment with nintedanib or pirfenidone.
- •Other investigational therapy received within 1 month or 6 half-lives (whichever was greater) prior to screening visit (Visit 1).
- •Use of any of the following medications for the treatment of Interstitial Lung Disease (ILD): azathioprine (AZA), cyclosporine, Mycophenolate Mofetil (MMF), tacrolimus, oral corticosteroids (OCS) >20mg/day and the combination of OCS+AZA+ n-Acetylcysteine (NAC) within 4 weeks of Visit 2, cyclophosphamide within 8 weeks of Visit 2, rituximab within 6 months of Visit
- •Note: Patients whose Regulatory Authority (RA)/Connective Tissue Disease (CTD) is managed by these medications should not be considered for participation in the current study unless change in RA/CTD medication is medically indicated.
- •Further exclusion criteria apply.
研究组 & 干预措施
150 mg Nintedanib
A soft gelatin capsule of 150 mg Nintedanib was administered orally twice daily (bid) in Chinese patients with chronic fibrosing ILD with progressive phenotype with over 52 weeks. Dose could be reduced to 100 mg bid to manage adverse events.
干预措施: Nintedanib (Drug)
Placebo
A soft gelatin capsule of placebo matching in size, weight, colour and shape to 150 milligram (mg) or 100 mg soft gelatin capsule of Nintedanib, was administered orally twice daily (bid) in Chinese patients with chronic fibrosing Interstitial Lung Disease (ILD) with progressive phenotype with over 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks Expressed in Milliliter (mL)
时间窗: From baseline up to Week 52.
Annual rate of decline in FVC over 52 weeks expressed in milliliter (mL). The main analysis used a restricted maximum likelihood (REML)-based approach with a random slope and intercept model. The analysis included the fixed, categorical effects of treatment, high resolution computed tomography (HRCT) pattern at baseline, fixed continuous effects of time and baseline FVC as well as the treatment-by-time and baseline-by-time interactions. Random effects were included for the patient response for both time and intercept. For patients who prematurely discontinued study treatment, data collected at follow-up visit and visits after treatment discontinuation was included in the analysis.
次要结局
未报告次要终点