1) Study assessments have been changed to decrease the number of 12-lead electrocardiograms (ECGs) because no abnormalities in the ECGs potentially caused by pirfenidone were detected. 2) Clarification has been added on subjects to sign informed consent form prior to washout or discontinuation of prohibited medication. 3) Screening period has been changed to clarify that subjects stop commercial Esbriet and switch to pirfenidone provided as study drug based on feedback received during feasibility testing that there is an obligation in some countries to supply subjects with study medication once eligibility is confirmed. 4) Changes have been made to reflect that collection of unused pirfenidone need to be done, and dosing adherence, AEs and concomitant medications need to be reviewed, which is necessary as subject receives study drug from Screening Day to Day 21. 5) Relevant sections have been changed to clarify the allowance of down-titration for both study medication used in this trial.

1) Excluded subjects with clinical evidence of active infection only if, according to the investigator, the infection would interfere with the study conduct, measurement of pulmonary function, or impact the course of IPF. 2) Excluded all subjects with any degree of hepatic impairment, based on an updated United States Package Insert (USPI) for nintedanib. 3) Excluded all subjects with hypersensitivity to peanuts or soy, and added soy products and soy lecithin-containing products as prohibited foods. 4) The requirement for a urine pregnancy test at Baseline was removed, as a serum pregnancy test was already required at Baseline. 5) Revised the Schedule of Assessments to include collection of Forced expiratory volume at 1 second (FEV1) at Screening and Baseline and to include the King’s Brief Interstitial Lung Disease (KBILD) questionnaire at the Early Discontinuation Visit. 6) Schedule of Assessment was revised to include monthly urine pregnancy testing for women of childbearing potential, based on a request by the Health Authorities in Germany. 7) The option for blood samples for laboratory tests to be drawn by a home nursing agency was added. 8) Clarified the timing for providing informed consent prior to entering the Washout Period, and clarified the procedure for tapering (down titration) of prohibited medications during the Washout Period. 9) Revised the assessment of laboratory parameters to specify c-reactive protein (CRP) as a separate measurement, and to remove hemoglobin A1c. 10) Added a third independent data monitoring committee (iDMC) meeting when approximately 75% of the total subject group had either completed 24 weeks of combination treatment or had permanently discontinued study treatments.

11) Added a Biomarker Study to the protocol for the purpose of assessing the pharmacodynamic effect of nintedanib on pirfenidone- or IPC-related biomarkers. 12) Revised the Safety Population definition. 13) Corrected the confidence intervals (CIs) from 80% to 95% for reporting the number and proportion of subjects who completed 24 weeks on pirfenidone at a dose of 1602 to 2403 mg/day and nintedanib at a dose of 200 to 300 mg/day, and the number and proportion of subjects who discontinued combination treatment because of an AE. 14) Updated the embryo-fetal toxicity of nintedanib and updated the pirfenidone pregnancy wording. 15) Updated the impact on pirfenidone treatment due to a photosensitivity reaction or rash and gastrointestinal side effects. 16) Added hepatic side effects as a safety measure to be analyzed. 17) Revised contraception requirements after the final Follow-up Visit and updated reporting requirements related to hospitalizations, pregnancy, and post-study AEs. 18) Clarified that all adverse event of special interests (AESIs) needed to be reported within 24 hours after learning of the event.