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

Completed · Phase 3 · Has a placebo group

Conditions studied: Lung Diseases, Interstitial

In brief

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 Idiopathic Pulmonary Fibrosis (IPF), it is anticipated that Nintedanib will be a new treatment option for patients with PF-ILD.

Key facts

Study ID

NCT02999178

Run by

Boehringer Ingelheim

People needed

663

Starts

2017-01-17

Expected to finish

2019-08-12

Last updated by the study team

2020-05-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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].

Where it is running

• Cedars-Sinai Medical Center — Los Angeles, California, United States
• University of California Los Angeles — Los Angeles, California, United States
• University of California Davis — Sacramento, California, United States
• University of California San Francisco — San Francisco, California, United States
• National Jewish Health — Denver, Colorado, United States
• Pulmonary and Sleep Specialists — Danbury, Connecticut, United States
• Yale University School of Medicine — New Haven, Connecticut, United States
• Pulmonary and Sleep of Tampa Bay — Brandon, Florida, United States
• University of Florida College of Medicine — Jacksonville, Florida, United States
• University of Miami — Miami, Florida, United States
• Emory University — Atlanta, Georgia, United States
• Northwestern University — Chicago, Illinois, United States
• University of Chicago — Chicago, Illinois, United States
• Loyola University Medical Center — Maywood, Illinois, United States
• University of Kansas Medical Center — Kansas City, Kansas, United States
• University of Kentucky Medical Center — Lexington, Kentucky, United States
• University of Maryland School of Medicine — Baltimore, Maryland, United States
• Johns Hopkins Hospital — Baltimore, Maryland, United States
• Pulmonary and Critical Care Associates of Baltimore — Towson, Maryland, United States
• Brigham and Women's Hospital — Boston, Massachusetts, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Pulmonary and Critical Care Medicine — Ann Arbor, Michigan, United States
• Henry Ford Health System — Detroit, Michigan, United States
• Spectrum Health — Grand Rapids, Michigan, United States
• University of Alabama at Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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