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Effect of Nintedanib on Biomarkers of Extracellular Matrix Turnover in Patients With Idiopathic Pulmonary Fibrosis and Limited Forced Vital Capacity Impairment

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02788474
First Posted: June 2, 2016
Last Update Posted: September 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
  Purpose
Identifying biomarkers to predict the clinical course and benefits of therapy early in the course of the disease remains one of the most urgent and relevant challenges to improve overall patient management, to prevent treatment delay or overtreatment. This study is conducted to examine the effect of nintedanib treatment on change in biomarkers indicative of extracellular matrix turnover which have been shown recently to correlate with disease progression. This study further aims to confirm the association of biomarker course during the first three months of treatment and disease progression.

Condition Intervention Phase
Idiopathic Pulmonary Fibrosis Drug: nintedanib Drug: placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: A 12-week, Double Blind, Randomised, Placebo Controlled, Parallel Group Trial Followed by a Single Active Arm Phase of 40 Weeks Evaluating the Effect of Oral Nintedanib 150 mg Twice Daily on Change in Biomarkers of Extracellular Matrix (ECM) Turnover in Patients With Idiopathic Pulmonary Fibrosis (IPF) and Limited Forced Vital Capacity (FVC) Impairment.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The rate of change (slope) in blood C-reactive protein degraded by metalloproteinase-1/8 (CRPM) from baseline to week 12. [ Time Frame: baseline and 12 weeks ]

Secondary Outcome Measures:
  • The proportion of patients with disease progression as defined by absolute forced vital capacity decline >=10% or death until week 52 [ Time Frame: 52 weeks ]
  • The rate of change in blood Collagen 3 degraded by metalloproteinase-9 (C3M) from baseline to week 12 [ Time Frame: baseline and 12 weeks ]
  • The rate of change in blood Collagen 1 degraded by metalloproteinase-2/9/13 (C1M) from baseline to week 12 [ Time Frame: baseline and 12 weeks ]

Enrollment: 347
Actual Study Start Date: June 9, 2016
Estimated Study Completion Date: June 11, 2018
Primary Completion Date: August 4, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo Drug: placebo
Experimental: nintedanib Drug: nintedanib

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Written informed consent consistent with International Conference on Harmonisation Good Clinical Practice 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 Idiopathic pulmonary fibrosis (IPF) within the last 3 years from visit 0, based upon the American Thoracic Society/ European Respiratory Society /Japanese Respiratory Society/ Latin American Thoracic Association 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 Idiopathic pulmonary fibrosis;
  • Forced vital capacity (FVC) >=80% of predicted normal at Visit 1.

Exclusion criteria:

  • Alanine transaminase, Aspartate aminotransferase > 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 Forced expiratory volume in 1 second / Forced vital capacity < 0.70;
  • 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 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 any 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 any 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 pregnancy (ß-HCG) test at Visit 1 and/or Visit 2;
  • Women of childbearing potential4 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;
  • Patients who are or have been participating in another trial with investigational drug/s within one month prior to Visit 1 and patients who have previously been enrolled in this trial;
  • Further exclusion criteria apply.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02788474


  Show 82 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02788474     History of Changes
Other Study ID Numbers: 1199.227
2015-003148-38 ( EudraCT Number )
First Submitted: May 27, 2016
First Posted: June 2, 2016
Last Update Posted: September 12, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial
Nintedanib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action