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

Lung Diseases, Interstitial Clinical Trial

— INBUILD®  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02999178
• Other study ID #: 1199.247
• Secondary ID: 2015-003360-37
• Status: Completed
• Phase: Phase 3
• Start date: January 17, 2017
• Est. completion date: August 12, 2019

Study information

• Verified date: April 2020
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 663
• Est. completion date: August 12, 2019
• Est. primary completion date: April 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Interstitial

Intervention

Drug:
• Nintedanib

• Placebo

Locations

Country	Name	City	State
Argentina	Centro Dr. Lazaro Langer S.R.L	Alberdi Sur
Argentina	Centro de Investigaciones Metabólicas (CINME)	C.a.b.a
Argentina	Sanatorio Güemes	Ciudad Autónoma de Bs As
Argentina	CEMER-Centro Medico De Enfermedades Respiratorias	Florida
Argentina	INSARES	Mendoza
Argentina	Instituto Médico de la Fundación Estudios Clínicos	Rosario
Belgium	Centre Hospitalier Universitaire de Liège	Angleur
Belgium	ULB Hopital Erasme	Bruxelles
Belgium	UZ Leuven	Leuven
Belgium	Yvoir - UNIV UCL de Mont-Godinne	Yvoir
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	CHUS Fleurimont	Sherbrooke	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Concordia Hospital	Winnipeg	Manitoba
Chile	Hospital Clínico Reg. de Concepción "Dr. G. Grant Benavente"	Concepción
Chile	Instituto Nacional del Tórax	Providencia, Santiago De Chile
Chile	Centro de Investigación del Maule	Talca
China	Peking Union Medical College Hospital	Beijing
China	First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	Nanjing Drum Tower Hospital	Nanjing
China	The First Hospital of Chinese Medical University	Shenyang
France	HOP Avicenne	Bobigny
France	HOP Louis Pradel	Bron
France	HOP Côte de Nacre	Caen
France	HOP d'Instruction des Armées Percy	Clamart
France	HOP Calmette	Lille
France	HOP Nord	Marseille
France	HOP Arnaud de Villeneuve	Montpellier
France	HOP Pasteur	Nice
France	HOP Bichat	Paris
France	HOP Maison Blanche	Reims
France	HOP Pontchaillou	Rennes
France	HOP Civil	Strasbourg
France	HOP Bretonneau	Tours
Germany	Universitätsklinikum Bonn AöR	Bonn
Germany	Fachkrankenhaus Coswig GmbH	Coswig
Germany	Klinik Donaustauf	Donaustauf
Germany	Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH	Essen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg	Heidelberg
Germany	Wissenschaftliches Institut Bethanien	Solingen
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Petrus-Krankenhaus	Wuppertal
Italy	A.O.U. Policlinico Vittorio Emanuele	Catania
Italy	Ospedale "G.B. Morgagni - L. Pierantoni" ausl forli	FORLì
Italy	Azienda Ospedaliera Policlinico di Modena	Modena
Italy	A.O. San Gerardo di Monza	Monza
Italy	Policlinico Gemelli	Roma
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena
Japan	Tosei General Hospital	Aichi, Seto
Japan	Kurume University Hospital	Fukuoka, Kurume
Japan	Sapporo Medical University Hospital	Hokkaido, Sapporo
Japan	National Hospital Organization Himeji Medical Center	Hyogo, Himeji
Japan	Kobe City Medical Center General Hospital	Hyogo, Kobe
Japan	Ibarakihigashi National Hospial	Ibaraki, Naka-gun
Japan	Kanagawa Cardiovascular and Respiratory Center	Kanagawa, Yokohama
Japan	Saiseikai Kumamoto Hospital	Kumamoto, Kumamoto
Japan	Tohoku University Hospital	Miyagi, Sendai
Japan	Nagasaki University Hospital	Nagasaki, Nagasaki
Japan	National Hospital Organization Kinki-Chuo Chest Medical Center	Osaka, Sakai
Japan	Osaka Medical College Hospital	Osaka, Takatsuki
Japan	Hamamatsu University Hospital	Shizuoka, Hamamatsu
Japan	Jichi Medical University Hospital	Tochigi, Shimotsuke
Japan	Tokushima University Hospital	Tokushima, Tokushima
Japan	Nippon Medical School Hospital	Tokyo, Bunkyo-ku
Japan	Tokyo Medical and Dental University	Tokyo, Bunkyo-ku
Japan	Toranomon Hospital	Tokyo, Minato-ku
Japan	JR Tokyo General Hospital	Tokyo, Shibuya-ku
Japan	Global Health and Medicine Ctr	Tokyo, Shinjuku-ku
Korea, Republic of	The Catholic University of Korea, Bucheon St.Mary's Hospital	Bucheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Poland	University Clinical Center, Gdansk	Gdansk
Poland	Leszek Giec Upper-Silesian Med.Cent.Silesian Med.Univ.	Katowice
Poland	Norbert Barlicki University Clinical Hospital No.1, Lodz	Lodz
Poland	Nat.Instit.of Tuberculosis&LungDiseases,Outpat.Clin,warszawa	Warszawa
Poland	Clinical Hospital No. 1, n.a. Prof. Szyszko from Silesian MA	Zabrze
Russian Federation	Res.Inst.-Compl.Iss.Cardi.Dis.	Kemerovo
Russian Federation	Central Scientific Research Insitute of Tuberculosis	Moscow
Russian Federation	Moscow 1st State Med.Univ.n.a.I.M.Sechenov	Moscow
Russian Federation	Pulmonology Scientific Research Institute	Moscow
Russian Federation	Scientific Research Institute of Pulmonology	St. Petersburg
Russian Federation	Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl	Yaroslavl
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Puerta del Mar	Cádiz
Spain	Hospital de Galdakao	Galdakao
Spain	Hospital de Bellvitge	L'Hospitalet de Llobregat
Spain	Hospital La Paz	Madrid
Spain	Hospital La Princesa	Madrid
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Son Espases	Palma de Mallorca
Spain	Hospital de Canarias	San Cristóbal de La Laguna
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Politècnic La Fe	Valencia
United Kingdom	University Hospital Llandough	Cardiff
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent
United States	Pulmonary and Critical Care Medicine	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Pulmonary and Sleep of Tampa Bay	Brandon	Florida
United States	The Lung Research Center, LLC	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of South Carolina	Columbia	South Carolina
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Pulmonary and Sleep Specialists	Danbury	Connecticut
United States	National Jewish Health	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Medical Campus	Falls Church	Virginia
United States	Texas Pul & Crit Care Conslt	Fort Worth	Texas
United States	Spectrum Health	Grand Rapids	Michigan
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Florida College of Medicine	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center-New York Presbyterian Hospital	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NewYork-Presbyterian/Weill Cornell Medical Center	New York	New York
United States	Temple University Hospital	Oaks	Pennsylvania
United States	Creighton University	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	The Oregon Clinic	Portland	Oregon
United States	The Oregon Clinic	Portland	Oregon
United States	Pulmonary Associates of Richmond, Inc.	Richmond	Virginia
United States	Mayo Clinic, Rochester	Rochester	Minnesota
United States	University of California Davis	Sacramento	California
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Diagnostics Research Group	San Antonio	Texas
United States	Medical Arts and Research Center (MARC)	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	Pulmonary and Critical Care Associates of Baltimore	Towson	Maryland
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Chile,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annual Rate of Decline in Forced Vital Capacity - Overall Population	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Overall population consists of all randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only or HRCT fibrotic pattern= Other fibrotic patterns. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in the overall population is based on a random coefficient regression with fixed effects for treatment, HRCT fibrotic pattern, and baseline FVC [mL], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.	Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Primary	Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only is based on a random coefficient regression with fixed effects for treatment, baseline FVC [mL], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.	Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Secondary	Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population	King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were >50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in the overall population was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.	Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Secondary	Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were >50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.	Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Secondary	Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population	Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.	From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Secondary	Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.	From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Secondary	Time to Death Over 52 Weeks - Overall Population	Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.	From first drug intake until date of death or last contact date, up to 372 days
Secondary	Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.	From first drug intake until date of death or last contact date, up to 372 days
Secondary	Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population	Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.	From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Secondary	Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.	From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Secondary	Time to Progression or Death Over 52 Weeks - Overall Population	Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when = 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.	From first drug intake until date of progression or date of death or last contact date, up to 372 days
Secondary	Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when = 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.	From first drug intake until date of progression or date of death or last contact date, up to 372 days
Secondary	Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).	Baseline and up to 52 weeks after first drug intake
Secondary	Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).	Baseline and up to 52 weeks after first drug intake
Secondary	Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).	Baseline and up to 52 weeks after first drug intake
Secondary	Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).	Baseline and up to 52 weeks after first drug intake
Secondary	Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population	Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were =50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).	Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Secondary	Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were =50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).	Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Secondary	Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population	Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were =50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).	Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Secondary	Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only	Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were =50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).	Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)

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