Effect of nintedanib on biomarkers

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 490

Inclusion Criteria

-Written informed consent consistent with ICH-GCP and local laws, signed prior to participation in the trial including any study related procedures being performed;
- Male or female patients aged =40 years at Visit 1;
- A clinical diagnosis of IPF within the last 3 years from visit 0, based upon the ATS/ERS/JRS/ALAT 2011 guideline;
- Chest high resolution computed tomography (HRCT) scan performed within 18 months of Visit 0;
- Combination of HRCT pattern, and surgical lung biopsy pattern (the latter if available) as assessed by central review are consistent with the diagnosis of IPF;
- FVC =80% of predicted normal at Visit 1.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

- ALT, AST > 1.5 fold upper limit of normal (ULN) at visit 1;
- Total bilirubin > 1.5 fold ULN at visit 1;
- Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment);
- Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC <0.7 at visit 1);
- History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of visit 1;
- Bleeding Risk:
-- Known genetic predisposition to bleeding;
-- Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin etc.) or high dose antiplatelet therapy;
-- History of haemorrhagic central nervous system (CNS) event within 12 months prior to visit 1;
-- History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to visit 1;
-- International normalised ratio (INR) > 2 at visit 1;
-- Prothrombin time (PT) and partial thromboplastin time (PTT) > 150% of ULN at visit 1;
- Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery;
- History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1;
- Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault formula at Visit 1;
- Treatment with nintedanib, pirfenidone, azathioprine, cyclophosphamide, cyclosporine, any other investigational drug, n-acetylcysteine, prednisone/prednisolone >15 mg daily or >30 mg every 2 days OR use of other systemic corticosteroids as well as other investigational drugs within 4 weeks of visit 2;
- Known hypersensitivity to nintedanib, peanut, soya or to any other components of the study medication;
- Prior discontinuation of nintedanib treatment due to intolerability/ adverse events considered drug related;
- A disease or condition which in the opinion of the investigator may interfere with testing procedures or put the patient at risk when participating in this trial;
- Alcohol or drug abuse which in the opinion of the treating physician would interfere with the treatment and would affect patient's ability to participate in this trial;
- Patients not able to understand and follow study procedures such as but not limited to home spirometry, including completion of self-administered questionnaires without help;
- Women who are pregnant, nursing, who plan to become pregnant while in the trial or female patients with positive ß-HCG test at visit 1 and/or visit 2;
- Women of childbearing potential not willing or able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly;
- Patients with acute IPF exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 or during the screening period.
Visit 1 and/or Visit 2 should be postponed in case of an IPF exacerbation or respiratory tract infection. Refer to Section 6.1 for information on re-scheduling of visits;
- Patients who are currently participating in another trial or who have been participating in another trial within one month prior to Visit 1, and patients who have previously been enrolled in this trial.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the trial will be to assess the effect of nintedanib on rate of change in extracellular matrix (ECM) turnover biomarker CRPM over 12 weeks which has shown to strongly associate with disease progression in patients with IPF in the PROFILE cohort.<br>;Secondary Objective: A secondary objective is to confirm the observed results from the PROFILE cohort, i.e. to assess the predictive value of change in extracellular matrix (ECM) biomarkers CRPM, C1M and C3M over 12 weeks for disease progression as defined by FVC decline =10% or death over 52 weeks. ;Primary end point(s): 1: The rate of change (slope) in blood CRPM from baseline to week 12.<br>;Timepoint(s) of evaluation of this end point: 1: 12 weeks<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The key secondary endpoint<br>1: Proportion of patients with disease progression as defined by absolute FVC (% predicted) decline =10% or death until week 52 based on in clinic supervised spirometry.<br><br>Secondary endpoints: <br>2: Rate of change (slope) in blood C1M from baseline to week 12 3: Rate of change (slope) in blood C3M from baseline to week 12.<br>;Timepoint(s) of evaluation of this end point: 1: 52 weeks<br>2: 12 weeks<br>3: 12 weeks<br>