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Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD) (PF-ILD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Boehringer Ingelheim
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02999178
First received: December 19, 2016
Last updated: April 18, 2017
Last verified: April 2017
  Purpose
The aim of the current study is to investigate the efficacy and safety of nintedanib over 52 weeks in patients with Progressive Fibrosing Interstitial Lung Disease (PF-ILD) defined as patients who present with features of diffuse fibrosing lung disease of >10% extent on high-resolution computed tomography (HRCT) and whose lung function and respiratory symptoms or chest imaging have worsened despite treatment with unapproved medications used in clinical practice to treat ILD. There is currently no efficacious treatment available for PF-ILD. Based on its efficacy and safety in Idiopatic Pulmonary Fibrosis (IPF), it is anticipated that Nintedanib will be a new treatment option for patients with PF-ILD.

Condition Intervention Phase
Lung Diseases, Interstitial
Drug: Nintedanib
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (masked roles unspecified)
Primary Purpose: Treatment
Official Title: A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib Over 52 Weeks in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Annual rate of decline in Forced Vital Capacity [ Time Frame: 52 weeks ]

Secondary Outcome Measures:
  • Absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) total score at week 52 [ Time Frame: 52 weeks ]
  • Time to first acute ILD exacerbation or death over 52 weeks [ Time Frame: 52 weeks ]
  • Time to death over 52 weeks [ Time Frame: 52 weeks ]
  • Time to death due to respiratory cause over 52 weeks [ Time Frame: 52 weeks ]
  • Time to progression (defined as a equal or more than 10 percent absolute decline in Forced Vital Capacity (FVC) percent pred) or death over 52 weeks [ Time Frame: 52 weeks ]
  • Proportion of patients with a relative decline from baseline in Forced Vital Capacity (FVC) percent pred of more than 10 percent at week 52 [ Time Frame: 52 weeks ]
  • Proportion of patients with a relative decline from baseline in Forced Vital Capacity (FVC) percent pred of more than 5 percent at week 52 [ Time Frame: 52 weeks ]
  • Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms dyspnea domain score at week 52 [ Time Frame: 52 weeks ]
  • Absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms cough domain score at week 52 [ Time Frame: 52 weeks ]

Estimated Enrollment: 600
Actual Study Start Date: January 17, 2017
Estimated Study Completion Date: November 15, 2019
Estimated Primary Completion Date: July 12, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nintedanib Drug: Nintedanib
Placebo Comparator: Placebo Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 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 Harmonised Tripartite Guideline for 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 Computer Tomography (HRCT) to reviewer).
  • Male or female patients aged >= 18 years at Visit 1.
  • Patients with physician diagnosed Interstitial Lung Disease (ILD) who fulfil at least one of the following criteria for Progressive Fibrosing Interstitial Lung Disease (PF-ILD) 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 (refer to Exclusion Criteria):

    • Clinically significant decline in Forced Vital Capacity (FVC) % pred based on a relative decline of >=10%
    • Marginal decline in FVC % pred based on a relative decline of .>=5-<10% combined with worsening of respiratory symptoms
    • Marginal decline in FVC % pred 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 1.
  • Carbon Monoxide Diffusion Capacity (DLCO) corrected for Haemoglobin (Hb) [visit 1] ≥ 30% and <80% predicted of normal at Visit 2
  • FVC >= 45% predicted at Visit 2

Exclusion criteria:

  • Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) > 1.5 x Upper Limit of Normal (ULN) at Visit 1
  • Bilirubin > 1.5 x ULN at Visit 1
  • Creatinine clearance <30 mL/min calculated by Cockcroft-Gault formula at Visit 1 [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, MMF, tacrolimus, oral corticosteroids (OCS) >20mg/day and the combination of OCS+AZA+NAC within 4 weeks of Visit 2, cyclophosphamide within 8 weeks of Visit 2, rituximab within 6 months of Visit 2.

Note: Patients whose Rheumatoid Arthritis (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 (see Inclusion Criteria)

  • Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 2011 Guidelines.
  • Significant Pulmonary Arterial Hypertension (PAH) defined by any of the following:

    • Previous clinical or echocardiographic evidence of significant right heart failure
    • History of right heart catheterization showing a cardiac index <= 2 l/min/m²
    • PAH requiring parenteral therapy with epoprostenol/treprostinil
    • Primary obstructive airway physiology (pre-bronchodilator FEV1/FVC < 0.7 at Visit 1).
    • In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
  • Major extrapulmonary physiological restriction (e.g. chest wall abnormality, large pleural effusion)
  • Cardiovascular diseases, any of the following:

    • Severe hypertension, uncontrolled under treatment (≥160/100 mmHg), within 6 month of Visit 1
    • Myocardial infarction within 6 months of Visit 1
    • Unstable cardiac angina within 6 months of Visit 1
  • Bleeding risk, any of the following:

    • Known genetic predisposition to bleeding.
    • Patients who require

      • Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin)
      • High dose antiplatelet therapy. [Note: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 I.U. s.c. per day), as well as prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited].
    • History of haemorrhagic central nervous system (CNS) event within 12 months of Visit 1.
    • Any of the following within 3 months of Visit 1:

      • Haemoptysis or haematuria
      • Active gastro-intestinal (GI) bleeding or GI - ulcers
      • Major injury or surgery (Investigators judgment).
    • Coagulation parameters: International normalized ratio (INR) >2, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) by >1.5 x ULN at Visit 1.
  • History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1.
  • Known hypersensitivity to the trial medication or its components (i.e. soya lecithin)
  • Patients with peanut allergy.
  • Other disease that may interfere with testing procedures or in the judgment of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial.
  • Life expectancy for disease other than ILD < 2.5 years (Investigator assessment).
  • Planned major surgical procedures.
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
  • 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 as well as one barrier method for 28 days prior to and 3 months after nintedanib administration. A list of contraception methods meeting these criteria is provided in the patient information.
  • In the opinion of the Investigator, active alcohol or drug abuse.
  • Patients not able to understand or follow trial procedures including completion of self-administered questionnaires without help. *A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02999178

Contacts
Contact: Boehringer Ingelheim Call Center 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

  Show 139 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02999178     History of Changes
Other Study ID Numbers: 1199.247
2015-003360-37 ( EudraCT Number )
Study First Received: December 19, 2016
Last Updated: April 18, 2017

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Interstitial
Respiratory Tract Diseases
Nintedanib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 28, 2017