A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of GLPG1690 in Addition to Local Standard of Care for Minimum 52 Weeks in Subjects With Idiopathic Pulmonary Fibrosis
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Sponsor: Galapagos NV

CONFIDENTIALITY STATEMENT 
The information contained in this document is privileged and confidential. It is the property of Galapagos NV and may not be 
used, disclosed, reproduced or otherwise disseminated within your organization or communicated to any third parties without 
the express written authorization of Galapagos NV. 
 
CLINICAL STUDY PROTOCOL 
Project Number: 
GLPG1690 
 
Study Number: 
GLPG1690-CL-303 
Study Title: 
A Phase 3, randomized, double-blind, parallel-group, placebo-
controlled multicenter study to evaluate the efficacy and safety of 
two doses of GLPG1690 in addition to local standard of care for 
minimum 52 weeks in subjects with idiopathic pulmonary 
fibrosis. 
Development Phase: 
3 
Status: 
Final 
CSP Version: 
7.00 
Date: 
8-Jun-2020 
Amendment 5 
EudraCT No.: 
2018-001405-87 
CT.gov No.: 
NCT03711162 
IND No.: 
130687 
Sponsor: 
Galapagos NV, Generaal De Wittelaan L11 A3, 2800 Mechelen, 
Belgium 
Study Physician: 
, MD 
General Protocol  
 

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EMERGENCY CONTACT INFORMATION 
In case of a serious adverse event (SAE) or in case of pregnancy during the clinical study the 
investigator must report this immediately, and under no circumstances later than 24 hours 
following the knowledge of the SAE or pregnancy, as follows:  
 SAE Fax #: 
 
or 
E-mail: 
 
In case of medical questions during the course of the study, the investigator must contact the 
contract research organization (CRO) Medical Monitor or, if unavailable, his/her back-up. 
Please refer to the study contact list in the investigator site file for the CRO medical contact 
details.  
 
 
 
Sponsor Contact number: 
  

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TABLE OF CONTENTS 
Clinical Study Protocol ............................................................................................................ 1 
Emergency Contact Information ............................................................................................ 2 
Table of Contents ..................................................................................................................... 3 
Clinical Study Protocol History .............................................................................................. 7 
Summary of Changes ............................................................................................................... 8 
List of Abbreviations and Definition of Terms .................................................................... 22 
1. Summary ........................................................................................................................... 26 
2. Introduction ...................................................................................................................... 30 
2.1. Background - Nonclinical Studies ............................................................................ 31 
2.1.1. Physical, Chemical, Pharmaceutical Properties, and Formulations................. 31 
2.1.2. Pharmacology .................................................................................................. 31 
2.1.2.1. Primary and Secondary Pharmacology .............................................. 31 
2.1.2.2. Safety Pharmacology .......................................................................... 32 
2.1.3. Nonclinical Pharmacokinetics and Product Metabolism ................................. 32 
2.1.4. Toxicology ....................................................................................................... 33 
2.1.4.1. General Toxicology ............................................................................ 33 
2.2. Background - Clinical Studies .................................................................................. 35 
2.2.1. Clinical Safety ................................................................................................. 35 
2.2.2. Clinical Pharmacokinetics ............................................................................... 36 
2.2.3. Clinical Pharmacodynamics ............................................................................ 37 
3. Clinical Study Objectives ................................................................................................. 38 
3.1. Primary Objective ..................................................................................................... 38 
3.2. Secondary Objectives ................................................................................................ 38 
3.2.1. Key Secondary Objectives ............................................................................... 38 
3.2.2. Other Secondary Objectives ............................................................................ 38 
3.3. 
 ........................................................................................................ 39 
4. Investigational Plan .......................................................................................................... 39 
4.1. Clinical Study Design ............................................................................................... 39 
4.1.1. Definition of End of Trial ................................................................................ 41 
4.1.2. Guidance for dose modification in case of adverse events .............................. 41 
4.2. Clinical Study Rationale ........................................................................................... 44 
4.2.1. Dose Rationale ................................................................................................. 45 
4.2.2. Clinical Study Design Rationale ...................................................................... 45 
4.3. Endpoints ................................................................................................................... 46 
4.3.1. Primary Endpoint ............................................................................................. 47 
4.3.2. Secondary Endpoints ....................................................................................... 47 
4.3.2.1. Key Secondary Endpoints .................................................................. 47 
4.3.2.2. Other Secondary Endpoints ................................................................ 47 
4.3.3.
 ............................................................................................... 48 
4.4. Potential Risks and Benefits ...................................................................................... 48 
4.5. Clinical Study Population ......................................................................................... 51 
4.5.1. Inclusion Criteria ............................................................................................. 51 
4.5.2. Exclusion Criteria ............................................................................................ 52 
4.5.3. Prohibition and Restrictions ............................................................................ 54 
4.5.3.1. Precautions for Sexual Intercourse ..................................................... 54 
4.5.3.2. Prior and Concomitant Medications ................................................... 56 

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7.2.4. Per-Protocol Set ............................................................................................... 96 
7.2.5. Pharmacokinetic Analysis Set ......................................................................... 96 
7.2.6.
 ............................................................................. 96 
7.3. Statistical Analyses ................................................................................................... 97 
7.3.1. General Statistical Considerations ................................................................... 97 
7.3.2. Interim Analysis ............................................................................................... 97 
7.3.3. Analyses of Demographics and Baseline Characteristics ................................ 97 
7.3.4. Analyses of Efficacy Parameters ..................................................................... 97 
7.3.5. Analyses of Safety Data ................................................................................. 100 
7.3.5.1. Extent of Exposure ........................................................................... 101 
7.3.5.2. Adverse Events ................................................................................. 101 
7.3.5.3. Clinical Laboratory Evaluations ....................................................... 101 
7.3.5.4. Physical Examinations ...................................................................... 101 
7.3.5.5. Vital Signs ........................................................................................ 101 
7.3.5.6. Electrocardiogram ............................................................................ 101 
7.3.6. Pharmacokinetics and 
 .................................................... 102 
7.3.7.
 ..................................................................................... 102 
8. Data Monitoring ............................................................................................................. 102 
8.1. Independent Data Monitoring Committee .............................................................. 102 
8.2. Clinical Endpoint Adjudication Committee ............................................................ 103 
8.3. Additional Optional Independent Review of Safety Data ....................................... 103 
9. Safety Reporting ............................................................................................................. 103 
9.1. Definitions of Adverse Events, Serious Adverse Events, and Special 
Situations ................................................................................................................. 103 
9.1.1. Adverse Events .............................................................................................. 103 
9.1.2. Serious Adverse Events ................................................................................. 103 
9.1.3. Unlisted (Unexpected) Adverse Event/Reference Safety Information .......... 104 
9.1.4. Adverse Events of Special Interest ................................................................ 104 
9.1.5. Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events ................................................... 104 
9.1.6. Special Situations ........................................................................................... 104 
9.2. Assessment of Adverse Events and Serious Adverse Events ................................. 105 
9.2.1. Assessment of Causality ................................................................................ 105 
9.2.2. Assessment of Severity .................................................................................. 106 
9.2.3. Outcome ......................................................................................................... 106 
9.3. Investigator Requirements and Instructions for Reporting Adverse Events / 
Serious Adverse Events /Pregnancies and Other Special Situations to the 
Sponsor .................................................................................................................... 107 
9.3.1. Adverse Events .............................................................................................. 107 
9.3.2. Serious Adverse Events ................................................................................. 107 
9.3.3. Pregnancy ...................................................................................................... 108 
9.3.4. Reporting of Special Situations (Other Than Pregnancy) and Associated 
Adverse Events .............................................................................................. 108 
9.4. Sponsor Reporting Requirements ........................................................................... 108 
10. Sponsor’s and Investigator’s Responsibilities .............................................................. 109 
10.1. Sponsor’s Responsibilities ...................................................................................... 109 
10.1.1. Regulatory Approval / Notification ............................................................. 109 
10.1.2. Clinical Study Closure Considerations ........................................................ 109 
10.1.3. Indemnification ............................................................................................ 110 

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10.1.4. Insurance ...................................................................................................... 110 
10.1.5. Reporting ..................................................................................................... 110 
10.1.6. Publication ................................................................................................... 110 
10.2. Investigator’s Responsibilities ................................................................................ 111 
10.2.1. Financial Disclosure .................................................................................... 111 
10.2.2. Source Data and Data Capture ..................................................................... 111 
10.2.3. Archiving ..................................................................................................... 111 
10.2.4. Participation Cards ....................................................................................... 112 
10.3. Confidentiality ......................................................................................................... 112 
10.4. Ethical Considerations ............................................................................................ 112 
10.4.1. Independent Ethics Committee / Institutional Review Board ..................... 112 
10.4.2. Informed Consent ........................................................................................ 113 
10.5. Data Quality Control / Assurance ........................................................................... 114 
10.5.1. Monitoring ................................................................................................... 114 
10.5.2. Audit and Inspection .................................................................................... 114 
References ............................................................................................................................. 115 
Appendices ............................................................................................................................ 118 
Signature Page – Sponsor .................................................................................................... 131 
Signature Page – Investigator ............................................................................................. 132 
 
 

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SUMMARY OF CHANGES 
Amendment 5 (General) 
The overall reason for this amendment: is to implement the urgent safety measures (USMs) for 
protection of study subjects during the Coronavirus disease (COVID-19) pandemic. These were 
detailed in the USM letter dated 07 May 2020 and sent to investigators, Competent Authorities, 
Ethics Committees, and Institutional Review Boards. 
The USMs are introduced due to the exceptional situation generated by the COVID-19 pandemic. 
The objective of these USMs is to limit the risk of exposure to COVID-19 infection to ensure the 
safety and well-being of study subjects. 
The USMs are: 
− 
phone visits or televisits as alternative to on-site visits; 
− 
collection of study assessments at the subject's home or other remote location (if possible and 
available); 
− 
extension of visit windows; 
− 
additional guidance for on-site visits; 
− 
direct-to-patient (DTP) shipment of investigational medicinal product (IMP) and other supplies 
to the subject’s home; 
− 
additional guidance on the decision for continuation of IMP after missed visits. 
In addition:  
− Exclusion criterion 15 has been amended to include all lower respiratory tract infections 
requiring treatment, rather than those requiring antibiotic treatment. 
− Clarification has been added that the investigator will be responsible for managing COVID-19 
infected subjects. 
− Exclusion criterion 5 was modified to clarify that subjects are permitted to take stable doses of 
immunosuppressive medication for reasons other than treatment of idiopathic pulmonary fibrosis 
(IPF). 
− The possibility was added to perform source data review remotely when access to hospitals is 
restricted. 
− The international nonproprietary name, ziritaxestat, was added. 
The changes made to the clinical study protocol (CSP) GLPG1690-CL-303 Version 6.00 (17-Dec-
2019) are listed below, with a brief rationale of each change and the applicable sections. 
If a randomized subject is not able to attend a scheduled study visit on site for any COVID-19 
related reason, then the investigator should perform a phone call or use a virtual platform such as 
Skype, Facetime, etc., to evaluate safety and assess well-being of the study subject.  
Subject visits at home or at a remote location (other than the investigational site) can be considered 
at the investigator’s discretion. 
Applicable Sections: 
Section 4.1 Clinical Study Design 
Section 6 Clinical Study Assessments 
Section 6.1.1 Alternative Timing and Assessment Procedures for Subjects who, due to any 
Covid-19-related Reason, Cannot Perform the Study Procedures  
Section 6.11.1 Schedule of Activities: Screening and First 52 Weeks of Study Treatment 
Section 6.11.2 Schedule of Activities: After 52 Weeks of Study Treatment 

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Amendment 5 (General) 
To allow for the flexibility of obtaining safety and efficacy data when subjects are unable or 
unwilling to complete the study procedures due to any COVID-19-related issue, the visit windows 
for Visits 5, 6, 7, 8, 10, and 11 may be increased to ±7 days and the visit windows for Visit 9 and 
Visit 12 may be increased to ±28 days.  
Applicable Sections: 
Section 4.1 Clinical Study Design 
Section 6 Clinical Study Assessments 
Section 6.1.1 Alternative Timing and Assessment Procedures for Subjects who, due to any 
Covid-19-related Reason, Cannot Perform the Study Procedures  
Section 6.11.1 Schedule of Activities: Screening and First 52 Weeks of Study Treatment 
At all times, the intent should be to ensure that study subjects can continue to take IMP without 
interruptions, if safe and deemed appropriate by the investigator. Guidance on when IMP should be 
interrupted and on re-start is provided. 
Applicable Section: 
Section 6.1.1 Alternative Timing and Assessment Procedures for Subjects who, due to any 
Covid-19-related Reason, Cannot Perform the Study Procedures 
Information on the assessments/activities that should be performed (if possible) is provided for the 
on-site visits, for the home (or remote other location) visits, and for the phone/televisits. 
Applicable Sections: 
Section 4.1 Clinical Study Design 
Section 6 Clinical Study Assessments 
Section 6.1.1 Alternative Timing and Assessment Procedures for Subjects who, due to any 
Covid-19-related Reason, Cannot Perform the Study Procedures 
Section 6.4 Subject Diary Card 
Section 6.5.1.1 Spirometry 
Section 6.5.1.2 DLCO 
Section 6.5.1.3 
 
Section 6.5.3 Quality of Life 
Section 6.5.4 Functional Exercise Capacity Testing: 6MWT 
Section 6.6. Safety Assessments 
Section 6.6.5 Electrocardiogram 
Section 6.7 Pharmacokinetic Assessments 
Section 6.8 
 
Section 6.9.1 
 
Section 6.11.1 Schedule of Activities: Screening and First 52 Weeks of Study Treatment 
Section 6.11.2 Schedule of Activities: After 52 Weeks of Study Treatment 

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Amendment 5 (General) 
Exclusion criterion 15 has been amended to exclude all lower respiratory tract infections requiring 
treatment (rather than those requiring antibiotic treatment) within 4 weeks prior to screening and/or 
during the screening period. This is to exclude subjects with suspected or confirmed COVID-19 
lower respiratory tract infections.  
A clarification has been added that the investigator will be responsible for managing COVID-19 
infected subjects, and that the decision to continue or interrupt IMP for subjects with confirmed or 
suspected cases of COVID-19 infection is at the investigator’s discretion.  
Guidance for reporting of suspected and confirmed COVID-19 cases in randomized subjects has 
been added. 
Applicable Sections: 
Section 4.1.2 Guidance for Dose Modification in Case of Adverse Events 
Section 4.4 Potential Risks and Benefits 
Section 4.5.2 Exclusion Criteria 
Exclusion criterion 5 was modified to clarify that subjects are permitted to take stable doses of 
immunosuppressive medication for reasons other than treatment of idiopathic pulmonary fibrosis 
(IPF). 
The rationale is to ensure that subjects who are on immunosuppressives due to conditions other than 
IPF (such as post solid organ transplants and inflammatory bowel disease) are not excluded from 
the study. 
Applicable Section: 
Section 4.5.2 Exclusion Criteria 
If a randomized subject is not able to attend a scheduled study visit on site for any COVID-19 
related reason, IMP and other supplies can be shipped via DTP shipment to the study subject when 
required due to the COVID-19 situation as per ICH-GCP principles.  
Applicable Sections: 
Section 5.3 Packaging, Labelling, and Distribution 
Section 6.1.1 Alternative Timing and Assessment Procedures for Subjects who, due to any Covid 
19-related Reason, Cannot Perform the Study Procedures 
Section 6.4 Subject Diary Card 
The possibility was added to perform source data verification remotely.  
Applicable Section: 
Section 10.5.1 Monitoring 
The international nonproprietary name, ziritaxestat, has been added. 
Applicable Section: 
Section 2.1.1 Physical, Chemical, Pharmaceutical Properties, and Formulations 
 
 

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Amendment 4 (General) 
The overall reason for this amendment: is an update of the exclusion criteria, and addition of the 
possibility to receive investigational medicinal product (IMP) in an extension study. 
The changes made to the clinical study protocol (CSP) GLPG1690-CL-303 Version 5.00 (12 Nov 
2019), are listed below, with a brief rationale of each change and the applicable sections. 
The information on GLPG1690 has been updated according to Edition 6 of the Investigator’s 
Brochure (28-Jun-2019).  
Applicable Sections: 
Section 2 Introduction  
The possibility of IMP being offered to eligible subjects in an extension study has been added.  
Applicable Section: 
Section 4.1 Clinical Study Design 
Additional clarification is given with relation to study visits for subjects who permanently 
discontinue IMP but remain in the study. Subjects will still be encouraged to complete all following 
visits and evaluations as originally planned per protocol. If not possible to complete all visits, 
preference should be given to complete: 
• 
the first scheduled visit after their Early Treatment Discontinuation (ETD)  
• 
the Week 26 visit (if not done before IMP discontinuation) 
• 
the Week 52 visit (if not done before IMP discontinuation) 
• 
after Week 52, visits every 24 weeks up to End of Study Assessments (EoSA), as described 
in Section 6.11.2 
Applicable Sections: 
Section 4.1 Clinical study design 
Section 4.5.4 Treatment Discontinuation, Subject Withdrawal, and Study Termination 
For subjects still taking IMP and who had their last scheduled visit more than 6 weeks before the 
date that the last subject reaches 52 weeks into the study (Visit 12), the timing of the End of Study 
Treatment (EoST) visit has been reduced from 4 weeks to 2 weeks after the last subject reached 52 
weeks. 
Applicable sections: 
Section 4.1 Clinical Study Design 
Section 6.1 Timing of assessments 

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Amendment 4 (General) 
The description of the high-resolution computed tomography (HRCT) evaluation process for 
assessing eligibility has been removed from Section 4.1 and Section 6.1, and is now described and 
clarified in Appendix 1. 
Applicable sections: 
Section 4.1 Clinical study design 
Section 4.2.2 Clinical study design rationale 
Section 6.1 Timing of assessments 
Appendix 1 HRCT/biopsy central review criteria 
Events meeting the following defined criteria must be reported as a serious adverse event (SAE) and 
IMP must be discontinued: 
• 
AST or ALT ≥8xULN 
• 
AST or ALT ≥3xULN with signs of severe liver damage (i.e. with the appearance of 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or 
eosinophilia [>5%], and/or total bilirubin ≥1.5xULN or International Normalized Ratio 
[INR] >1.5)  
The investigations and steps to be taken by the investigator have been described in Section 4.5.4. 
In addition, an optional review of safety data associated with liver function tests has been added. 
Applicable Sections: 
Section 4.5.4 Treatment Discontinuation, Subject Withdrawal, and Study Termination 
Section 8.3 Additional optional independent review of safety data 
Section 9.1.5. Clinical laboratory abnormalities and other abnormal assessments as adverse events 
or serious adverse events 
Appendix 9 Algorithm for elevated liver function tests 
The collection of history of progression of disease, as defined by a relative decline in the forced 
vital capacity (FVC) of at least 10% of the predicted value, during the 1 year prior to screening has 
been included. 
Applicable Section: 
Section 6.3 Initial Subject and disease characteristics  
Suboxone was removed from the list of known strong Cytochrome P450 (CYP) CYP3A4 inhibitors 
because its constituents, naloxone and bupenophine are not known to be strong inhibitors. 
Azelastine was removed from the list of known potent P-glycoprotein (P-gp) inhibitors in Appendix 
6 because it is primarily used as a nasal spray to treat allergic rhinitis and as eye drops for allergic 
conjunctivitis, therefore the risk of drug-drug interaction is negligible.  
Applicable Section: 
Appendix 5 Known strong CYP3A4 inhibitors 
Appendix 6 Known potent P-gp inhibitors 

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Amendment 4 (General) 
It was clarified that decisions on eligibility for rescreening, permitted comedications, and 
discontinuation of treatment in case of worsening of IPF can be taken on a case-by-case basis by the 
investigator and in case of doubt can be discussed with the CRO medical monitor (as per study 
contact list) or sponsor’s study physician (if the former is not available). 
Applicable Sections: 
Section 4.5.3.2 Prior and concomitant medications 
Section 6.3 Initial subject and disease characteristics 
The timing when vital status should be collected for subjects who withdraw from the study has been 
clarified. 
Applicable Sections: 
Section 4.5.4 Treatment discontinuation, subject withdrawal, and study termination 
Section 6.11 Schedule of  Activities 
A table has been added to clarify the PK sampling times. 
Applicable Section: 
Section 6.7 Pharmacokinetic Assessments 
Typographical corrections were made to Appendices 3 and 4. 
Further clarifications and corrections have been made throughout the protocol. 
 
 
 
Amendment 3 (General) 
The overall reason for this amendment: is to add new data from the GLPG1690-CL-113 drug-
drug interaction study on interaction of GLPG1690 with nintedanib, and to change the IMP intake 
time for all subjects taking nintedanib to approximately 4 hours after the morning nintedanib dose.  
The changes made to the CSP GLPG1690-CL-303 Version 4.00 (11 Feb 2019), are listed below, 
with a brief rationale of each change and the applicable sections. 
Subjects taking nintedanib are recommended to take the daily dose of IMP at or after lunch, i.e. 
approximately 4 hours after the morning dose of nintedanib.  
All subjects taking nintedanib will be asked to indicate via a tick box on the diary card for each 
record of IMP whether the IMP administration was approximately 4 hours after the nintedanib 
morning dose.   
Applicable Sections: 
Section 4.4 Potential Risks and Benefits 
Section 5.2 Dosage and Administration 
Section 6.4 Subject Diary Card 

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Amendment 2 (General) 
The following clarifications and corrections have been made: 
− 
The liver function test (LFT) threshold at Visit 3 that would lead to IMP discontinuation for 
aspartate aminotransferase [AST] and alanine aminotransferase [ALT] has been corrected in 
Section 4.1.2 from ≥1.5 x  to <3 x upper limit of normal (ULN) to ≥1.5x ULN, and is now in 
line with exclusion criterion 22 and Section 4.6.4. 
− 
Figure 2 depicting the dose modification strategy has been updated for clarification. 
− 
The statement that IMP should not be administered to subjects with moderate to severe renal 
impairment has been corrected to only include severe renal impairment, in line with exclusion 
criterion 23.  
Applicable Sections: 
Section 4.1.2 Guidance for dose modification 
Section 4.1.2 Guidance for dose modification in case of adverse events 
Section 4.4 Potential risks and benefits – special populations 
Subject Eligibility. The clinical diagnostic requirements have been clarified and corrected. 
− 
Inclusion criterion 4: Diagnosis of IPF should be made using the guideline current at the time 
of diagnosis.  
− 
The reference to the ATS/ERS/JRS/ALAT diagnostic criteria 2011 has been corrected, and 
reference to the latest ATS/ERS/JRS/ALAT diagnostic criteria of 2018 has been added (Raghu 
G, Remy-Jardin M, Myers JL, et al. American Thoracic Society, European Respiratory Society, 
Japanese Respiratory Society, and Latin American Thoracic Society. “Diagnosis of Idiopathic 
Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.” Am J 
Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68). 
− 
Subjects with typical and probable usual interstitial pneumonia – idiopathic pulmonary fibrosis 
(UIP-IPF) pattern on high-resolution computed tomography (HRCT) will be eligible unless a 
historical lung biopsy, if available, is not in accordance with this diagnosis. Indeterminate UIP-
IPF pattern on HRCT will need confirmation through review of historical lung biopsy, if 
available.  
− 
The interval of 6 weeks before a patient can be rescreened was replaced by an interval 
determined at the investigator’s discretion, taking into account the inclusion and exclusion 
criteria. Rescreening with the purpose to repeat a HRCT scan, is not allowed.  
− 
The instructions for screening assessments have been clarified.  
Applicable Sections: 
Section 4.2.2 Clinical study design rationale 
Section 4.5.1 Inclusion criteria 
Section 6.1 Timing of assessments 
Section 6.3 Initial subject and disease characteristics 

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Amendment 2 (General) 
Section 4.5.2 Exclusion criteria 
The information on fertility has been updated with the results of nonclinical male and female 
fertility studies in rats.  
The recommendation for males to store sperm before taking part in the study has been removed, and 
replaced with guidance for male subjects to withdraw if they intend to father a child.  
Applicable Sections: 
Section 4.4 Potential risks and benefits 
Section 4.5.3.1.2 Precautions for sexual intercourse: male subjects 
Interactions 
− 
The information on interaction with transporters in nonclinical studies has been updated. 
− 
The clinical safety and clinical pharmacokinetics sections have been updated based on recent 
data from two drug-drug interaction studies, one study with itraconazole and voriconazole, and 
one study with pirfenidone and nintedanib. Increased exposures of nintedanib, one of the 
standard of care treatments for IPF, was observed when coadministered with GLPG1690. 
− 
Additional PK sampling has been introduced to assess nintedanib levels.  
− 
A population PK analysis for nintedanib and pirfenidone has been added in the Statistical 
methods section. 
Applicable Sections: 
Section 2.1.3 Nonclinical pharmacokinetics and product metabolism 
Section 2.2.1 Clinical Safety 
Section 2.2.2 Clinical Pharmacokinetics 
Section 4.4 Potential risks and benefits 
Section 6.1 Timing of assessments 
Section 6.3 Initial subject and disease characteristics 
Section 6.4 Subject diary card 
Section 6.7 Pharmacokinetic assessments 
Section 6.11 Schedule of activities 
Section 7.3.6 Pharmacokinetics 
 
The QTcF thresholds leading to discontinuation have been clarified, and the following has been 
added: 
− 
“If a normal QTcF is reported during the visit, but the central cardiologist reports it as 
abnormal (any of the two criteria above), then the IMP should be discontinued as soon as 
possible”  
Applicable Sections: 
Section 4.5.4 Treatment discontinuation, subject withdrawal, and study termination 

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Amendment 2 (General) 
The list of clinical laboratory tests has been revised  
− 
Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean 
corpuscular hemoglobin concentration (MCHC) have been added to the hematology parameters 
to reflect the standard panel of investigations typically used in the IPF patient population. 
− 
If creatine kinase (CK) is elevated, then CK-muscle/brain (CK-MB) is to be measured, to 
monitor for muscle breakdown indicative of coronary heart disease. 
− 
Amylase and lipase have been added to monitor risk of pancreatitis, a reported risk/ adverse 
drug reaction for nintedanib. 
Applicable Section: 
Section 6.6.2 Clinical laboratory evaluations 
Statistical analysis 
− 
The description of the statistical analysis of efficacy has been updated, to describe the 
determination of sample size multiple testing approach and multiplicity adjustment.  
− 
The proportion of St. George’s Respiratory Questionnaire (SGRQ) responders and the 
proportion of subjects with hospitalization analysis was changed from Fisher exact test to a 
logistic regression model 
− 
The derivation of the IPF-specific version of St. George’s Respiratory Questionnaire (SGRQ-I) 
(using 34 of the 50 test items) has been removed from the protocol (Yorke J, Jones P, and 
Swigris J. Development and validity testing of an IPF specific version of the St. George's 
Respiratory Questionnaire. Thorax, 2010;65(10):921 926). 
Some SGRQ items in SGRQ-I have weaker measurement properties than others when applied 
to patient populations other than the one for which SGRQ was developed. SGRQ-I has some 
missing components when derived from SGRQ.  
− 
 
Applicable Sections: 
Section 6.5.3 Quality of Life 
Section 7.1 Determination of sample size 
Section 7.3.4  Analyses of efficacy parameters 
The non-exhaustive list of strong CYP3A4 inducers and potent P-gp inducers has been modified. 
Phenobarbital was removed because it is already included within the barbiturate group, and 
glucocorticoids (prednisone or equivalent) at > 10mg/day was specified, because high doses of 
glucocorticoids have been reported to be potential CYP3A4 inducers. 
Instructions for subjects to avoid double-strength grapefruit juice, which is potentially a potent 
CYP3A4 inhibitor have been added. 
Applicable Section  
Section 4.5.3.3 Food and beverage restrictions 
Appendix 4 Known strong CYP3A4 inducers and potent P-gp inducers 
Voriconazole, a strong CYP3A4 inhibitor, has been added to the non-exhaustive list of strong 
CYP3A4 inhibitors in Appendix 5. 
Applicable Section  
Appendix 5 Known strong CYP3A4 inhibitors  

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Amendment 1  
The overall reason for this amendment: 
Changes to accommodate requests made under the 
 
Clarification of definition of End of Trial for reporting purposes 
Applicable Sections: 
Section 4.1 Clinical Study Design 
Subheading 4.1.1 added with clarified definition of end of trial 
Additional subheading 4.1.2 added for the subsection on Guidance for dose modification in case of 
adverse events 
The protocol was amended to require discontinuation when the criteria of liver enzymes AST or 
ALT ≥ 1.5 x ULN and / or  total bilirubin ≥ 1.5 x ULN  is met at Visit 3,  
Applicable Sections: 
Section 4.1.2, Section 4.5.4, Appendix 9 
Reference to description of highly effective contraception/preventive exposure measures in Section 
4.5.3.1 Precautions for Sexual Intercourse added to Inclusion criterion 11. 
Applicable Section: 
Section 4.5.1 Inclusion Criteria 
Exclusion Criteria 2 and 21 combined into revised exclusion criterion 2 
Replacement of exclusion criterion 21 with criterion to comply with the 
 
 
Applicable Section: 
Section 4.5.2 Exclusion Criteria 
Discontinuation to be mandatory for specified safety findings. 
Applicable Section: 
Section 4.5.4, Subsection: Discontinuation of IMP 
The wording “should be discontinued” was replaced by “will be discontinued”. 
Specification that statistical testing will be 2-sided. 
Applicable Sections: 
Section 7.1, Section 7.3.4 
Rationale for the sample size was added. 
Applicable Section: 
Section 7.1 
Clarification of the planned pooled data analysis of the two identical studies, GLPG1690-CL-303 
and GLPG1690-CL-304 
Applicable Section: 
Section 7.3.4 
The language related to the Declaration of Helsinki was updated to conform with EU Directives 
2001/20/EC and 2005/28/EC 
Applicable Sections: 
Section 10 

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Amendment 1  
The procedure for collection of informed consent of a patient unable to read and/or write was 
amended to comply with the 
 
Applicable Section: 
Section 10.4.2 
 
Update 1 
Minor edits and edits based on ad hoc IB update – General 
 
 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviations 
%FEV1 
percent predicted forced expiratory volume in 1 second 
%FVC 
percent predicted forced vital capacity 
6MWT 
6-Minute Walk Test 
AE 
adverse event 
ALAT 
Latin American Thoracic Association 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AT1 
angiotensin II receptor type 1  
ATC 
Anatomical Therapeutic Classification 
ATS 
American Thoracic Society 
ATX 
autotaxin  
AUC 
area under the plasma concentration-time curve 
AUC0-∞ 
area under the concentration-time curve from time 0 to infinity 
AUC0-24h 
area under the plasma concentration-time curve from time 0 to 
24 hours 
BLM 
Bleomycin 
BCRP 
breast cancer resistance protein 
b.i.d. 
bis in die, twice daily 
BSEP 
bile salt export pump 
BW 
body weight 
CCr 
estimated creatinine clearance, calculated according to 
Cockcroft-Gault calculation 
CEAC 
clinical endpoint adjudication committee 
CK 
creatine kinase 
Cmax 
maximum observed plasma concentration 
COVID-19 
Coronavirus disease 
CRO 
contract research organization 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTFG 
Clinical Trial Facilitation Group 
CTGF 
connective tissue growth factor 
CYP 
cytochrome P450 
DBP 
diastolic blood pressure 

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DDI 
drug-drug interaction 
DLCO 
diffusing capacity of the lung for carbon monoxide 
DTP 
direct-to-patient 
ECG 
Electrocardiogram 
Emax 
maximum effect (expressed as a percentage reduction from baseline) 
ENPP1/2 
ectonucleotide pyrophosphatase/phosphodiesterase 1 or 2 
eCOA 
electronic clinical outcome assessment  
EoSA 
end of study assessments 
EoST 
end of study treatment 
EQ-5D 
EuroQOL 5-Dimensions Questionnaire 
EQ-5D-3L 
3-level version of EuroQOL 5-Dimensions Questionnaire 
EQ VAS 
EuroQOL visual analogue scale 
ERS 
European Respiratory Society 
ETD 
early treatment discontinuation 
FAS 
full analysis set 
FC 
food consumption 
 
 
FEF25-75 
forced expiratory flow between 25% and 75% of exhaled volume 
FEV1 
forced expiratory volume in 1 second  
FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practices 
GLP 
Good Laboratory Practice 
GGT 
gamma glutamyl transferase 
Hb 
hemoglobin  
HIV 
human immunodeficiency virus 
HMA 
Heads of Medicines Agencies 
HRCT 
high-resolution computed tomography 
IB 
Investigator’s Brochure 
IC50 
50% inhibitory concentration (concentration resulting in 50% 
inhibition) 
IC80 
80% inhibitory concentration (concentration resulting in 80% 
inhibition) 

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ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
IDMC 
independent data monitoring committee 
IEC 
Independent Ethics Committee 
Imax 
predicted maximum concentration in the portal vein 
IMP 
investigational medicinal product 
INR 
International Normalized Ratio 
IPF 
idiopathic pulmonary fibrosis 
IRB 
Institutional Review Board 
IWRS 
interactive web response system 
JRS 
Japanese Respiratory Society 
K-BILD 
King's Brief Interstitial Lung Disease 
LB 
lung biopsy 
LC-MS/MS 
liquid chromatography with tandem mass spectrometry 
LCQ 
Leicester Cough Questionnaire 
LFT 
liver function test 
LPA 
lysophosphatidic acid 
LPC 
lysophosphatidylcholine  
LPD 
lysophospholipase D 
MCID 
Minimal Clinical Important Difference 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
NOAEL 
no observed adverse effects level 
OATP 
organic anion transporting polypeptide 
OCT1 
organic cation transporter 1 
 
 
PDE 
Phosphodiesterase 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic(s) 
PLA 
phospholipase A 
PLC 
phospholipase C 
q.d. 
quaque die, once daily 

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QTc 
corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
QTcV 
QT interval corrected for heart rate using Van de Water’s formula 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
SGRQ 
St. George’s Respiratory Questionnaire 
SpO2 
oxygen saturation 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
TGFβ 
transforming growth factor β 
tmax 
time to maximum observed plasma concentration 
UGT 
uridine 5’-diphospho-glucuronosyltransferase 
UIP-IPF 
usual interstitial pneumonia – idiopathic pulmonary fibrosis 
ULN 
upper limit of the normal range 
VAS 
Visual Analogue Scale 
Vss 
volume of distribution at steady state 
WBC 
white blood cell 
WHO 
World Health Organization 
WOCBP 
women of child bearing potential 
 
Definition of Terms 
BMI 
weight (kg) / (height [m])2 
CCr 
estimated creatinine clearance, calculated according to 
Cockcroft-Gault calculation: 
CCr (in mL/min) = [(140-age) x weight]/[72 x SCr] (x 0.85 for women), 
with SCr = serum creatinine in mg/dL, age in years and weight in kg 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula: 
QTcF = QT/RR⅓, with RR = mean interval duration between 
consecutive RR peaks 
QTcV 
QT interval corrected for heart rate using Van de Water’s formula: 
QTcV = QT − 0.087 (60/HR − 1), with HR = heart rate 
 
 

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1. 
SUMMARY 
Objectives: 
Primary Objective 
− To evaluate the efficacy of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with idiopathic pulmonary fibrosis (IPF) as evaluated 
by the rate of decline of forced vital capacity (FVC) over a period of 52 weeks 
Secondary Objectives 
Key Secondary Objectives 
− To evaluate the impact of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with IPF on: 
• disease progression defined as deterioration of FVC or all-cause mortality at 
52 weeks 
• respiratory-related hospitalization until the end of the study 
• changes in quality of life (measured by St. George’s Respiratory Questionnaire 
[SGRQ] total score) at 52 weeks 
Other Secondary Objectives 
− To evaluate the efficacy of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with IPF as evaluated by the rate of decline of FVC 
until the end of the study 
− To evaluate the impact of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with IPF on: 
• disease progression defined as deterioration of FVC or all-cause mortality until 
the end of the study 
• changes in quality of life (measured by SGRQ total score) until the end of the 
study 
• all-cause non-elective hospitalization until the end of the study 
• respiratory-related mortality until the end of the study 
• lung transplant until the end of the study 
• acute IPF exacerbation until the end of the study 
• all-cause mortality or lung transplant until the end of the study 
• all-cause mortality, or lung transplant, or qualifying for lung transplant until the 
end of the study 
• all-cause mortality, deterioration of FVC, or respiratory-related hospitalization 
until the end of the study 
• all-cause mortality or respiratory-related hospitalizations until the end of the 
study 
− To evaluate the effect of two doses of GLPG1690 in addition to local standard of care 
compared to placebo on the changes from baseline in FVC at 52 weeks and until the 
end of the study 
− To evaluate the safety and tolerability of two doses of GLPG1690 in addition to local 
standard of care compared to placebo until the end of the study 

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generally well tolerated. The current Phase 3 study is the next step in the clinical development 
of GLPG1690, evaluating the efficacy and safety of two doses of orally administered 
GLPG1690 (200 mg q.d. and 600 mg q.d.) compared to placebo in subjects with IPF in 
addition to local standard of care. 
Endpoints: 
Primary Endpoint 
− Rate of decline of FVC (in mL) over a period of 52 weeks 
Secondary Endpoints 
Key Secondary Endpoints 
− Disease progression defined as the composite endpoint of first occurrence of ≥10% 
absolute decline in percent predicted forced vital capacity (%FVC) or all-cause 
mortality at 52 weeks  
− Time to first respiratory-related hospitalization until the end of the study  
− Change from baseline in the SGRQ total score at 52 weeks  
Other Secondary Endpoints 
− Rate of decline of FVC (in mL) until the end of the study 
− Disease progression defined as the composite endpoint of first occurrence of ≥10% 
absolute decline in %FVC or all-cause mortality until the end of the study 
− Change from baseline in the SGRQ total score until the end of the study 
− Time to first all-cause non-elective hospitalization until the end of the study  
− Time to respiratory-related mortality until the end of the study  
− Time to lung transplant until the end of the study  
− Time to first acute IPF exacerbation until the end of the study  
− Time to all-cause mortality or lung transplant until the end of the study  
− Time to all-cause mortality, or lung transplant, or qualifying for lung transplant until the 
end of the study  
− Time to all-cause mortality, ≥10% absolute decline in %FVC, or respiratory-related 
hospitalizations until the end of the study 
− Time to all-cause mortality or respiratory-related hospitalizations until the end of the 
study 
− FVC analyses at 52 weeks and until the end of the study: 
• absolute and relative change from baseline of FVC and %FVC  
• absolute categorical change of %FVC until the end of the study: decrease by >5, 
increase by >5, and change within ≤5  
• absolute categorical change of %FVC until the end of the study: decrease 
by >10, increase by >10, and change within ≤10  
− Safety and tolerability over time until the end of the study  
− Changes from baseline in cough-related quality of life, assessed by the LCQ total score 
and domains over time, and the VAS Cough and Urge to Cough, at 52 weeks and until 
the end of the study 
− Changes from baseline in quality of life, assessed by the EQ-5D, K-BILD total score 
and domains over time, at 52 weeks and until the end of the study 

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2. 
INTRODUCTION 
For details of GLPG1690, refer to the Investigator’s Brochure (IB) (Edition 6, 28-Jun-2019) 
and any relevant updates/addenda/errata. 
This clinical study will be conducted in accordance with the current International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical 
Practice (ICH-GCP) Guideline E6 (see also Section 10). 
Idiopathic Pulmonary Fibrosis 
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating, and 
ultimately lethal lung disease predominantly affecting elderly male smokers or ex-smokers with 
a median age of 65 to 70 years [5]. The disease is characterized by progressive worsening of 
dyspnea and lung function and is associated with a poor prognosis (i.e. median survival of 
2-5 years following diagnosis) [4, 12, 14, 18, 28]. 
The estimated IPF prevalence ranges from 14.0 to 27.9 cases per 100,000 population in the 
United States and from 1.3 to 23.4 cases per 100,000 population in Europe (data from 
1990-2011). The estimated IPF incidence in these studies ranges from 6.8 to 8.8 cases per 
100,000 population in the United States and from 0.2 to 7.4 cases per 100,000 population in 
Europe [8, 22, 31, 38]. 
Over the past decade, extensive research has been conducted to address the unmet medical need 
for effective IPF treatment. Two treatments (pirfenidone and nintedanib), targeting the 
biological processes that drive fibrosis, are currently approved in the European Union, the 
United States, and other regions around the world. Consequently, these treatments are standard 
of care for many patients. Pirfenidone (antifibrotic, anti-inflammatory, and antioxidant 
treatment marketed as e.g. Esbriet®; indicated in adults for the treatment of mild to moderate 
IPF), was the first drug to be licensed specifically for IPF. Phase 3 studies demonstrated that 
the drug improved progression-free survival and slowed the decline in forced vital capacity 
(FVC). Moreover, pirfenidone may have a mortality benefit [13, 23, 34, 37]. The drug was 
approved in the European Union in 2011 and in the United States in 2014. Nintedanib (tyrosine 
kinase inhibitor marketed as e.g. Ofev®; indicated in adults for the treatment of IPF), was 
initially developed as an anticancer agent. In Phase 3 studies, it significantly reduced the decline 
in FVC compared with placebo. A trend towards a reduced death rate was also observed; 
however, the studies were not designed to detect differences in mortality [32]. The drug was 
approved in the United States in 2014 and in the European Union in 2015. Both treatments 
appear to slow disease progression but are frequently associated with side effects potentially 
limiting their use in clinical practice [7, 24, 29]. 
There thus remains a considerable unmet medical need for the investigation and development 
of novel IPF treatments targeting disease-relevant pathways.  
The sponsor is currently pursuing the development of GLPG1690, a small-molecule autotaxin 
(ATX) inhibitor targeting disease-relevant signal transduction pathways, for the treatment of 
IPF. 

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Mode of Action 
GLPG1690 is a novel, potent, and selective small-molecule inhibitor of ATX. 
ATX, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) or 
lysophospholipase D (LPD), is a ~120 kDa protein that belongs to the ENPP family of enzymes. 
ATX is the only ENPP enzyme with LPD activity and is responsible for the hydrolysis of 
lysophosphatidylcholine (LPC) to produce the bioactive lipid lysophosphatidic acid (LPA). The 
term LPA covers several chemical species able to activate LPA receptors depending on the 
nature of the fatty acid side chain on the glycerol backbone. The most abundant LPA species in 
human plasma is LPA C18:2 with a fatty acid side chain of 18 carbon atoms including 
two unsaturated bonds [2]. Literature data have identified the ATX/LPC axis as the main source 
of LPA in blood [36, 39].  
Several publications suggest a role for ATX in the control of disease-affected lung function 
through effects on lung epithelial cells, fibroblasts, and smooth muscle cells [17]. In general, 
inflammatory conditions in the lung are often described as associated with increased ATX and 
LPA levels. Studies related to IPF indicated an increase in LPA levels in the bronchoalveolar 
lavage fluid of patients [35], an increase of ATX levels in human fibrotic lung [25], and an 
elevation of LPA C22:4 in exhaled breath condensate of patients [20]. Further, LPA1 knock-out 
and inhibitor studies revealed a key role for LPA in fibrotic processes in lung and were 
complemented by studies using cell-specific knock-out mice lacking ATX in bronchial 
epithelial cells and macrophages. These mice were shown to be less sensitive to models of lung 
fibrosis [25]. The role of LPA in lung remodeling relates to the effects of LPA on both lung 
fibroblasts (through LPA1) and epithelial cells (through LPA2). It has been demonstrated that 
LPA2 plays a key role in the activation of transforming growth factor β (TGFβ) in epithelial 
cells under fibrotic conditions [40].  
Available literature and preclinical pharmacology data generated by the sponsor, suggest that 
interventions targeting the ATX/LPA pathway could lead to a new class of therapy for IPF. 
2.1. 
BACKGROUND - NONCLINICAL STUDIES 
2.1.1. Physical, Chemical, Pharmaceutical Properties, and Formulations 
The chemical name of GLPG1690 (international nonproprietary name ziritaxestat) is 2-[[2-
ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-
a]pyridin-3-yl](methyl)amino]-4-(4-fluorophenyl)-1,3-thiazole-5-carbonitrile. 
The clinical formulation used in this study is a film-coated tablet. 
2.1.2. Pharmacology 
2.1.2.1. 
Primary and Secondary Pharmacology 
GLPG1690 is an ATX inhibitor (50% inhibitory concentration [IC50] of 131 nM and 224 nM 
in biochemical assays with human enzyme and mouse enzyme, respectively). The 
LPA production after human plasma incubation was inhibited by GLPG1690 with an IC50 of 
242 nM, demonstrating the low impact of plasma protein binding on the activity of the 
compound. The compound was selective over related enzymes like ENPP1, phosphodiesterase 
(PDE)4 and PDE5, and phospholipase A (PLA) and phospholipase C (PLC). Moreover, 

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After oral administration, drug-related material is excreted mainly in feces in rat (about 90% or 
greater). In bile duct-cannulated rats, about 50% of orally administered radioactivity was 
recovered in bile. 
Upon repeated once daily (q.d.) oral dosing of GLPG1690, no significant accumulation was 
observed in plasma, except in male rats (20 mg/kg/day) and dogs (50/65 mg/kg/day at 
Week 39). Gender differences in PK profiles were observed in rats but not in dogs. 
The total plasma clearance of GLPG1690 was low in mice, rats, monkeys, and dogs, ranging 
between 3% and 23% of the hepatic blood flow. Therefore, GLPG1690 is expected to undergo 
a low first-pass effect after oral dosing.  
The primary cytochrome P450 (CYP) enzyme involved in GLPG1690 metabolism was 
CYP3A4. In vitro metabolism studies in hepatocytes revealed 26 potential metabolites. 
Metabolites formed in human hepatocytes were all present to a similar or higher extent in rat 
and/or dog hepatocytes, the animal species selected for toxicity studies. 
An in vitro study with GLPG1690 in human hepatocytes showed no clinically relevant 
induction of human CYP2B6 and CYP2C enzymes. Regarding CYP1A2 and CYP3A4, weak 
induction cannot be excluded at a GLPG1690 dose of 600 mg q.d. in human, with a maximal 
decrease of around 30% in the exposure of a sensitive probe substrate for both CYP enzymes. 
An in vitro study with GLPG1690 in human liver microsomes indicated no clinically relevant 
inhibition of the majority of CYP enzymes. Weak competitive reversible inhibition of CYP2C8 
and CYP3A4/5 cannot be excluded at a GLPG1690 dose of 600 mg q.d. in human, with a 
maximal increase of approximately 1.7- and 1.5-fold, respectively, in the exposure of a sensitive 
probe substrate. 
In addition, GLPG1690 demonstrated a strong time-dependent, irreversible inhibition potential 
against CYP2C8-mediated metabolism. This could likely lead to a pronounced interaction with 
a sensitive CYP2C8 probe substrate (increased exposure) if co-administered with a GLPG1690 
dose of 600 mg q.d. in human. 
No interaction by GLPG1690 is expected for renal uptake transporters organic cation 
transporter (OCT)2, organic anion transporter (OAT)1 and OAT3 and hepatic efflux 
transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). For the hepatic 
uptake transporters organic anion transporter polypeptide OATP) OATP1B1, OATP1B3, and 
OCT1, and efflux transporters MATE1 (hepatic/renal) and MATE2K (renal) a clinical 
interaction with GLPG1690 cannot be ruled out; however substantial interactions are not 
anticipated. For the intestinal efflux P-gp and BCRP transporters and the hepatic efflux bile salt 
export pump (BSEP) transporters an interaction cannot be ruled out. 
2.1.4. Toxicology 
2.1.4.1. 
General Toxicology 
A comprehensive toxicology program has been conducted with GLPG1690. This program 
includes Good Laboratory Practice (GLP) oral repeat-dose toxicity studies of up to 26 weeks in 
rats and 39 weeks in dogs, embryofetal development studies in rats and rabbits, fertility studies 
in male and female rats, non-TgrasH2 mice preliminary studies, preliminary carcinogenicity 

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studies, and in vivo and in vitro genotoxicity studies. Additional toxicology studies conducted 
include phototoxicity studies and dose-range finding studies in rats and dogs. 
In rats, no GLPG1690-related mortality was observed. The dose-limiting adverse effects 
consisted of reduced food consumption (FC) and markedly decreased body weight (BW) gain 
at 1,000 mg/kg/day in the 4-week toxicity study, histopathological changes in the testes with 
reduced sperm parameters at ≥130 mg/kg/day in the 13- and 26-week GLP studies, and the 
presence of vacuolated alveolar macrophages, with alveolar amorphous material and 
perivascular inflammatory cell infiltration in the lungs of females in the 26-week GLP study. 
The no observed adverse effects level (NOAEL) values in rats were set at 40 and 130 mg/kg/day 
in males and females, respectively, in the 26-week GLP study.  
In repeat oral dose toxicity studies in dogs, the dose-limiting effects consisted of decreased 
white blood cell (WBC) count and FC, emesis and BW loss, associated with poor clinical 
conditions at doses ≥100 mg/kg/day in the 13- and 39-week GLP studies, respectively. . 
QT prolongation, which was considered non-adverse, was also observed in repeat oral dose 
toxicity studies in dogs (4-, 13-, and 39-week studies).. Additional findings in dogs consisted 
of adverse altered sperm parameters and inflammatory cell infiltrates in the liver and minimal 
bile duct hyperplasia at 150/100 mg/kg/day (in the 13-week GLP toxicity study). The safety 
margins obtained from the mean (AUC) exposures at the NOAEL for dogs in the 39-week study 
when compared with the highest clinical dose currently being tested in healthy subjects (600 mg 
q.d. Study GLPG1690-CL-116) was 31-fold.  
Male and female fertility studies in rats showed that there were no effects of GLPG1690 on 
mating performance, fertility, or reproduction in either male or female rats at the different 
dose levels tested. As the effects on sperm and testis proved reversible and had no functional 
impact on animal fertility parameters, the risk of an impact on male fertility in adult subjects 
is considered low. In males, the no observed effect level (NOEL) for mating performance and 
fertility was set at 400 mg/kg/day and the NOAEL for sperm changes was determined at 
40 mg/kg/day; the latter is in line with previous studies (i.e., 13 week rat study). In females, 
the NOEL for mating performance and fertility was considered to be 120 mg/kg/day. 
In reproductive embryofetal development studies with GLPG1690 in rats and rabbits, major 
external, visceral, and skeletal abnormalities were seen in fetuses of both species as well as 
increased incidences of postimplantation losses. In rats, the maternal and developmental 
NOAELs were determined at 60 mg/kg/day and 10 mg/kg/day, respectively. In rabbits, the 
maternal and developmental NOAELs were determined at 15 mg/kg/day and 5 mg/kg/day.  
GLPG1690 showed no genotoxic effects in vitro or in vivo. 
GLPG1690 showed a phototoxic potential in vitro. However, this potential has not been 
confirmed in a rat in vivo study, investigating the phototoxic effects on the eyes and the skin in 
female pigmented Long-Evans rats. No evidence of cutaneous or ocular phototoxicity was 
noted at doses of 100 and 300 mg/kg.  

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2.2. 
BACKGROUND - CLINICAL STUDIES 
2.2.1. Clinical Safety 
As of the safety data cut-off date of IB Edition 6, in clinical pharmacology studies, GLPG1690 
had been administered to 85 healthy subjects as single doses (dose range: 20 to 1500 mg), to 96 
healthy subjects in repeated doses (dose range: 100 to 1000 mg for either 7 or 14 days). 
Administration of GLPG1690 was considered safe and well tolerated during these studies. No 
deaths, serious treatment-emergent adverse events (TEAEs), or TEAEs leading to 
investigational medicinal product (IMP) discontinuation were reported after dosing with 
GLPG1690. All GLPG1690 TEAEs were at most moderate in severity. In Study GLPG1690-
CL-109, one SAE (ECG repolarization abnormality) was reported after a single dose of 
nintedanib, but before dosing with GLPG1690 (IMP). 
The safety profile of single doses of nintedanib and pirfenidone in Study GLPG1690-CL-109 
both alone and in combination with GLPG1690 was consistent with the respective nintedanib 
and pirfenidone prescribing information. 
An additional DDI study (GLPG1690-CL-113) evaluated the effect of multiple oral doses of 
GLPG1690 on the safety and tolerability of nintedanib 150 mg twice daily (b.i.d.) under 
different dosing conditions; i.e. the GLPG1690 dose and the timing of GLPG1690 
administration versus the nintedanib morning intake. Subjects received 150 mg nintedanib b.i.d. 
on Days 1 and 7, and GLPG1690 200 mg q.d. 0 (i.e. concomitantly) or 2 hours after nintedanib 
morning intake time, or 600 mg q.d. 0, 2, or 4 hours after the nintedanib morning intake time 
on Days 3 to 9. Cohorts 1 and 2 evaluated the morning and evening PK of nintedanib (150 mg 
b.i.d.) when administered alone and when the morning dose was administered simultaneously 
with GLPG1690 200 mg (in Cohort 1) or 600 mg (in Cohort 2). Cohorts 3 and 4 evaluated the 
morning and evening PK of nintedanib 150 mg b.i.d. when administered alone and in 
combination with GLPG1690 200 mg or 600 mg administered 2 h or 4 h after the nintedanib 
morning dose (i.e., 600 mg 2 h [Cohort 3a]; 600 mg 4 h [Cohort 3b] or 200 mg 2 h [Cohort 4a]).  
There were no serious adverse events and all TEAEs were at most moderate in severity. There 
was one TEAE (herpes zoster) that led to discontinuation of treatment in the cohort that received 
GLPG1690 200 mg at the same time as the nintedanib morning dose. GLPG1690 at doses of 
200 mg and 600 mg q.d. was well-tolerated. 
The frequency of TEAEs was generally similar between cohorts and treatments. The frequency 
of diarrhea adverse events was higher in most cohorts after nintedanib alone than after 
GLPG1690 alone. In contrast to the previous DDI study (GLPG1690-CL-109), the incidence 
of diarrhea events did not increase when nintedanib was administered with GLPG1690. 
Administration of oral doses of GLPG1690 600 mg q.d. for 12 weeks in 17 subjects with IPF 
was well tolerated (Phase 2a study GLPG1690-CL-202). No deaths were reported. Serious 
TEAEs were experienced by one subject in the GLPG1690 600 mg q.d. group 
(cholangiocarcinoma, led to permanent discontinuation) and by two subjects in the placebo 
group (atrioventricular block second degree in one subject, led to permanent discontinuation; 
and lower respiratory tract infection, urinary tract infection, and acute kidney injury in the other 
subject). None of these serious TEAEs were considered related to IMP according to the 
investigator. No notable differences were observed in the incidences of treatment-emergent 

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abnormalities between subjects with IPF treated with GLPG1690 600 mg q.d. or placebo. The 
majority of TEAEs were mild to moderate in severity.  
2.2.2. Clinical Pharmacokinetics 
Single (up to 1,500 mg) and multiple ascending oral doses of GLPG1690 (up to 1,000 mg q.d.) 
for 14 days were assessed in healthy male subjects under fed conditions. GLPG1690 was 
rapidly absorbed with a median time to maximum plasma concentration (tmax) of 0.5-2 h. Steady 
state exposure of GLPG1690 increased approximately in proportion with the dose between 300 
to 1,000 mg total daily. Excretion of unchanged GLPG1690 in human urine was low (<1.8% in 
24 hours [h] based on unchanged GLPG1690) and rapid. There was no impact on the urinary 
6β-OH-cortisol/cortisol ratio after repeated dosing suggesting a lack of CYP3A4 induction by 
GLPG1690.  
The PK of GLG1690 was similar between Caucasian and Japanese healthy male subjects. The 
PK of GLPG1690 in subjects with IPF was not markedly different from those observed in 
healthy subjects at the same dose level. 
Food decreased the rate of absorption of GLPG1690 given as tablet (as expected by delay in 
gastric emptying), but there was no clinically relevant difference in the bioavailability of 
GLPG1690. A higher between-subject variability was observed in fasted state, with 4 subjects 
out of 12 having 5- to 10-fold lower exposure than the other subjects. The rate of elimination 
was not impacted by food. The mean terminal half-life (t1/2) after a single 600 mg dose as tablets 
was approximately 11 h. 
After q.d. dosing with the strong CYP3A4/potent P-gp inducer rifampin for 10 days, 
GLPG1690 (600 mg q.d.) exposure was decreased (by 6.0- and 9.3-fold for maximum observed 
plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 
to 24 h [AUC0-24h], respectively) without any significant change in the apparent rate of 
elimination.  
Exposure of GLPG1690, as measured by area under the concentration-time curve from time 0 
to infinity (AUC0-∞), was 3- and 4-fold greater when administered in combination with 
itraconazole and voriconazole, respectively, than when GLPG1690 was administered alone. 
Maximum exposure (Cmax) of GLPG1690 increased slightly following administration of 
GLPG1690 in combination with itraconazole or voriconazole compared with administration of 
GLPG1690 only (Cmax values were 1.4-fold greater following administration in combination 
with itraconazole or voriconazole). This increase is unlikely to be clinically significant. 
GLPG1690 can therefore be classified as a moderately sensitive substrate of CYP3A4 as it 
demonstrated an increase in AUC of ≥2 to <5-fold with strong index inhibitors. Comparison of 
the plasma profiles showed no impact on the apparent rate of elimination of GLPG1690. 
The potential impact of GLPG1690 600 mg on the PK of single doses of pirfenidone and 
nintedanib was evaluated. Exposure of pirfenidone and its metabolite 5-carboxypirfenidone, as 
measured by Cmax, AUC0-∞, and terminal elimination half-life (t1/2) was not affected when 
administered in combination with GLPG1690, compared to when pirfenidone was administered 
alone. Exposure of nintedanib, as measured by Cmax, AUC0-∞ was approximately 2-fold greater 
when administered in combination with GLPG1690, than when GLPG1690 was administered 
alone. Nintedanib t1/2 was not affected by coadministration of GLPG1690. 

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3. 
CLINICAL STUDY OBJECTIVES 
3.1. 
PRIMARY OBJECTIVE 
− To evaluate the efficacy of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with IPF as evaluated by the rate of decline of FVC over 
a period of 52 weeks 
3.2. 
SECONDARY OBJECTIVES 
3.2.1. Key Secondary Objectives 
− To evaluate the impact of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with IPF on: 
• disease progression defined as deterioration of FVC or all-cause mortality at 
52 weeks 
• respiratory-related hospitalization until the end of the study 
• changes in quality of life (measured by St. George’s Respiratory Questionnaire 
[SGRQ] total score) at 52 weeks 
3.2.2. Other Secondary Objectives 
− To evaluate the efficacy of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with IPF as evaluated by the rate of decline of FVC until 
the end of the study 
− To evaluate the impact of two doses of GLPG1690 in addition to local standard of care 
compared to placebo in subjects with IPF on: 
• disease progression defined as deterioration of FVC or all-cause mortality until the 
end of the study 
• changes in quality of life (measured by SGRQ total score) until the end of the 
study 
• all-cause non-elective hospitalization until the end of the study 
• respiratory-related mortality until the end of the study 
• lung transplant until the end of the study 
• acute IPF exacerbation until the end of the study 
• all-cause mortality or lung transplant until the end of the study 
• all-cause mortality, or lung transplant, or qualifying for lung transplant until the 
end of the study 
• all-cause mortality, deterioration of FVC, or respiratory-related hospitalization 
until the end of the study 
• all-cause mortality or respiratory-related hospitalizations until the end of the study 
− To evaluate the effect of two doses of GLPG1690 in addition to local standard of care 
compared to placebo on the changes from baseline in FVC at 52 weeks and until the end 
of the study 
− To evaluate the safety and tolerability of two doses of GLPG1690 in addition to local 
standard of care compared to placebo until the end of the study 
− To evaluate changes compared to placebo in subjects with IPF in:  

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Figure 1: 
Schematic Study Overview 
D=Day, EoST/EoSA=end of study treatment/end of study assessments, FU=follow-up, V=Visit, W=Week. 
Enrolled subjects will come to the clinical study center at screening (two visits from Day -28 to 
Day -1). Visit 2 of screening can only take place after confirmed IPF diagnosis on HRCT and 
LB (if applicable) (for details, refer to Section 6.3 and Appendix 1). 
For the in- and exclusion criteria, please refer to Section 4.5.1 and Section 4.5.2, respectively. 
At Visit 3, eligible subjects will be randomized in a 1:1:1 ratio to receive 
GLPG1690 600 mg q.d., GLPG1690 200 mg q.d., or matching placebo for at least 52 weeks. 
Randomization will be stratified for background local standard of care for treatment of IPF. 
Subjects will come to the clinical study center on Day 1 (baseline), Weeks 2, 4, 8, 12, 18, 26, 
34, 42, 52, and every 12 weeks thereafter. Additional unscheduled visits are allowed if, in the 
investigator’s opinion, further evaluation (clinical, laboratory, or other) is needed. 
When the last subject reaches 52 weeks (Visit 12), subjects still taking IMP and who had a 
scheduled visit at the clinical study center within 6 weeks before this date will be contacted by 
their investigator (phone call) to discontinue IMP within 7 days after this date. Then the last 
scheduled visit will be documented as the end of study treatment (EoST) visit. These subjects 
will be invited to their follow-up visit scheduled at the clinical study center 4 weeks after their 
last dose of IMP (±7 days). For subjects still taking IMP and who had their last scheduled visit 
more than 6 weeks before the date that the last subject reaches 52 weeks into the study 
(Visit 12), a scheduled visit will be planned within 2 weeks of this date for an EoST visit, 
followed by a follow-up visit 4 weeks later (visit at clinical center or phone call). Note that 
these subjects will continue IMP intake until their EoST visit. 
For subjects who, for any Coronavirus disease (COVID-19)-related reason, cannot perform 
study procedures, extended visit windows, the possibility to conduct phone/televisits and home 
(or other remote location) visits, and alternative assessment procedures are detailed in Section 
6.1.1. 
Subjects who discontinue IMP early (early treatment discontinuation [ETD]), with the 
exception of patients lost to follow-up and patients who withdraw consent, will be encouraged 
to complete all following visits and evaluations as originally planned per protocol.  

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In particular, the subject will be requested if at all possible to attend:  
− 
the first scheduled visit after their Early Treatment Discontinuation (ETD)  
− 
The Week 26 visit (if not done before IMP discontinuation) 
− 
the Week 52 visit (if not done before IMP discontinuation) 
− 
after Week 52, visits every 24 weeks up to End of Study Assessments (EoSA), as 
described in Section 6.11.2 
For procedures in case of ETD, refer to Section 4.5.4. In the exceptional case that a clinical 
study center visit cannot be attended, a phone call by the investigator will be made to evaluate 
safety, in combination with scheduled clinical study center visits. 
Each subject will have a screening period of maximum 28 days. The duration of study treatment 
for individual subjects will vary from 52 weeks for the last enrolled subject to e.g. 132 weeks 
for the first enrolled subject (assuming a recruitment period of 80 weeks, the actual duration 
will depend on the actual time to recruit subjects for the study). A follow-up visit (at the clinical 
study center or by phone call, decided by the investigator) is planned 4 weeks after the 
EoST/end of study assessment (EoSA) visit.  
At the end of this study, treatment with IMP in an optional extension study (under a separate 
study protocol) may be offered to all eligible subjects, provided Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) and Competent Authority approvals for such an 
extension are granted.  
To protect the safety and integrity of the study data, an independent data monitoring committee 
(IDMC) will be implemented, as well as a clinical endpoint adjudication committee (CEAC). 
Charters are in place for all committees. For additional information, refer to Sections 8.1 (for 
IDMC) and 8.2 (for CEAC). 
For detailed information regarding dosage form, packaging, and labeling of the IMP, please 
refer to Sections 5.2 and 5.3. 
4.1.1. Definition of End of Trial 
The global end of trial will be reached when the last subject has completed the last follow-up 
visit (scheduled clinical study center visit or phone call), i.e. four weeks (±7 days) after the end 
of study treatment (EoST) or end of study assessments (EoSA) visit (Section 4.1 and Section 
6.11.2). 
4.1.2. Guidance for dose modification in case of adverse events 
At any stage, the investigator can decide to permanently discontinue IMP for concerns 
regarding safety and tolerability, i.e. an AE, including clinically significant abnormal laboratory 
tests. For abnormal liver function tests (LFTs), specific guidance is described in Appendix 9. 
For the subsequent management of these AEs, the investigator can reduce the dose, interrupt, 
or permanently discontinue the IMP. Down-titration will be a one-step process to the lowest 
reduced dose. Once the AE has stabilized or improved, the dose can be increased again 
(re-escalation). For the re-escalation from the lowest reduced dose, an intermediate reduced 
dose level is required (Figure 2). 
 

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Down-titration to reduced dose level or interruption of IMP:  
− AST or ALT ≥3x to 5xULN without signs of severe liver damage**: 
Down-titrate to low (reduced) dose level or interrupt IMP for at least 2 weeks (to be 
decided by the investigator, based on the subject’s risk assessment). 
− AST or ALT ≥5x to 8xULN without signs of severe liver damage**: 
Interrupt IMP for at least 2 weeks.  
During these periods of at least 2 weeks: Re-test AST, ALT, alkaline phosphatase, total 
bilirubin, and eosinophils within 48 to 72 hours, approximately at 7 days, thereafter 
approximately at 14 days, and also assess signs of severe liver damage**. If local regulations 
allow, home visits can be performed if subjects cannot come to the clinical study center. 
Re-escalation after each period of at least 2 weeks at any dose level: 
− 
Remain on the highest tolerated dose at investigator’s discretion. Monitoring of LFTs can 
return to the planned study assessments once the LFTs have stabilized at the highest 
tolerated dose level for 8 weeks. 
− 
AST and ALT <3xULN: 
Re-escalate to the next dose level for at least 2 weeks, with regular LFT monitoring (weekly 
for the first 2 weeks, biweekly for the following weeks, or more frequently at investigator’s 
discretion) and repeat re-escalation to next higher dose level every 2 weeks (or longer at 
investigator’s discretion) if AST and ALT <3xULN.  
− 
AST or ALT ≥3xULN: 
Discontinue IMP.  
*Close observation is defined as: 
− Monitor two to three times per week all of the following parameters: ALT, AST, alkaline 
phosphatase, total bilirubin, eosinophils, and International Normalized Ratio (INR). If 
local regulations allow, home visits can be performed if subjects cannot come to the 
clinical study center. 
− Frequency of retesting can be reduced to once a week or less if abnormalities stabilize or 
the IMP has been discontinued; however, monitoring might still be needed more 
frequently taking into consideration the standard of care and/or changes to this. 
− Re-query history of symptoms, prior and concurrent diseases, concomitant medication and 
non-prescription medicines, herbal, dietary supplements, alcohol use, recreational drug 
use, special diets. 
− Rule out all of the following: acute viral hepatitis, auto-immune hepatitis, alcoholic 
hepatitis, non-alcoholic fatty hepatitis, hypoxic/ischemic hepatitis, biliary tract disease, 
and cholestasis. 
− Re-query exposure to environmental chemical agents. 
− Consider gastro-enterology or hepatology consultations. 
** Signs of severe liver damage:  
− Increase of liver transaminases is accompanied by appearance of fatigue, nausea, 
vomiting, right upper abdominal quadrant pain or tenderness, fever, rash and/or 
eosinophilia (>5%), and/or 
− Total bilirubin ≥1.5x ULN, or 
− INR >1.5. 

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Each blinded treatment kit will have blisters for the high (original) dose level, intermediate 
(reduced) dose level, and low (reduced) dose level, allowing the clinical study center to 
modulate the IMP dose for a particular subject, even without knowing the original treatment 
allocation (also see Section 5.2).  
The Investigator will be responsible for managing COVID-19 infected subjects and the 
decision to continue or interrupt IMP for subjects with confirmed or suspected cases of 
COVID-19 infection is at the investigator’s discretion. Guidance on continuation of IMP and 
requirements for assessments conducted during the COVID-19 pandemic are provided in 
Section 6.1.1. 
4.2. 
CLINICAL STUDY RATIONALE 
Since 2010, disease-modifying drugs such as pirfenidone and nintedanib are indicated for 
patients with IPF and available in most parts of the world. These drugs have been shown to 
have a beneficial effect on the rate of decline in lung function (as measured by FVC over 1 year) 
and show a trend in favor of a reduction in mortality [32]. Both drugs have received conditional 
recommendation for use in the American Thoracic Society (ATS) / European Respiratory 
Society (ERS) / Japanese Respiratory Society (JRS) / Latin American Thoracic Association 
(ALAT) 2015 guidelines [29].  
However, the residual decline of FVC over 1 year remains substantial, with a further decline of 
FVC over 52 weeks of 125 mL and 114 mL in INPULSIS I and II (nintedanib) [33], 
respectively, and around 200 mL in the ASCEND study (pirfenidone) [13].  
Additional therapies targeting different disease pathways could potentially prove to be more 
effective by further preventing the decline in FVC with an acceptable safety profile [41]. 
In the proof-of-concept Phase 2a study GLPG1690-CL-202, FVC values remained stable in the 
majority of subjects on GLPG1690 600 mg q.d. (+8 mL mean change from baseline). 
Moreover, 12 weeks of treatment with GLPG1690 600 mg q.d. was generally well tolerated 
(refer to Section 2.2.1).  
The current Phase 3 study is a next step in the clinical development of GLPG1690, evaluating 
the efficacy and safety of two doses of orally administered GLPG1690 (200 mg q.d. and 
600 mg q.d.) compared to placebo in subjects with IPF in addition to local standard of care.  
The primary objective of the study is to evaluate the efficacy of GLPG1690 in addition to local 
standard of care on the rate of decline of FVC over a period of 52 weeks. FVC has been accepted 
as a clinically relevant efficacy measure in IPF, as a benefit in terms of FVC decline showed a 
trend toward decreased mortality [11]. 
Key secondary objectives are to evaluate the effect on disease progression defined as 
deterioration of FVC (expressed as categorical decline of ≥10% predicted FVC) or all-cause 
mortality, respiratory-related hospitalizations, and quality of life as measured by SGRQ total 
score. 
All-cause and respiratory-related mortality have been chosen as other secondary objectives to 
provide supportive evidence that the treatment affects the disease. The effect on acute IPF 
exacerbation and patient-related outcomes such as quality of life, cough-related outcomes, and 
hospitalizations will also be evaluated. Safety and tolerability, GLPG1690, pirfenidone, and 

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4.3.1. Primary Endpoint 
− Rate of decline of FVC (in mL) over a period of 52 weeks. 
4.3.2. Secondary Endpoints 
4.3.2.1. 
Key Secondary Endpoints 
− Disease progression defined as the composite endpoint of first occurrence of ≥10% 
absolute decline in percent predicted forced vital capacity (%FVC) or all-cause mortality 
at 52 weeks  
− Time to first respiratory-related hospitalization until the end of the study  
− Change from baseline in the SGRQ total score at 52 weeks  
4.3.2.2. 
Other Secondary Endpoints 
− Rate of decline of FVC (in mL) until the end of the study 
− Disease progression defined as the composite endpoint of first occurrence of 
≥10% absolute decline in %FVC or all-cause mortality until the end of the study 
− Change from baseline in the SGRQ total score until the end of the study 
− Time to first all-cause non-elective hospitalization until the end of the study  
− Time to respiratory-related mortality until the end of the study  
− Time to lung transplant until the end of the study  
− Time to first acute IPF exacerbation until the end of the study  
− Time to all-cause mortality or lung transplant until the end of the study  
− Time to all-cause mortality, or lung transplant, or qualifying for lung transplant until the 
end of the study  
− Time to all-cause mortality, ≥10% absolute decline in %FVC, or respiratory-related 
hospitalizations until the end of the study  
− Time to all-cause mortality or respiratory-related hospitalizations until the end of the 
study 
− FVC analyses at 52 weeks and until the end of the study: 
• absolute and relative change from baseline of FVC and %FVC  
• absolute categorical change of %FVC until the end of the study: decrease by >5, 
increase by >5, and change within ≤5  
• absolute categorical change of %FVC until the end of the study: decrease by >10, 
increase by >10, and change within ≤10  
− Safety and tolerability over time until the end of the study  
− Changes from baseline in cough-related quality of life, assessed by the LCQ total score 
and domains over time, and the VAS Cough and Urge to Cough, at 52 weeks and until the 
end of the study 
− Changes from baseline in quality of life, assessed by the EQ-5D, K-BILD total score and 
domains over time, at 52 weeks and until the end of the study 
− Plasma concentration of GLPG1690, pirfenidone, and nintedanib (as appropriate) at 
52 weeks and until the end of the study 
− Change from baseline in functional exercise capacity, assessed by the 6MWT distance, at 
52 weeks and until the end of the study 

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The interaction (increased exposure of nintedanib) observed when GLPG1690 and nintedanib 
150 mg b.i.d. were administered concomitantly was reduced when GLPG1690 was 
administered 2 or 4 hours after the nintedanib morning dose.  
This clinical study protocol contains specific precautions and exclusions to manage use of 
GLPG1690 on top of standard of care (pirfenidone and nintedanib). The plasma concentrations 
of GLPG1690, pirfenidone and nintedanib will be collected. The potential for increased 
exposure to nintedanib when co-administered with GLPG1690, can be managed by separating 
the intake times of the morning dose of nintedanib and the IMP daily dose. It is therefore 
recommended that all subjects on nintedanib take IMP at or after lunch (approximately 4 hours 
after nintedanib morning intake);  refer to Section 5.2. Additionally all subjects taking 
nintedanib will be evaluated by monitoring adverse events and managing them according to the 
guidance in the nintedanib prescribing information. 
Management of adverse events 
For the management of AEs, guidance for the investigator should be followed, as described in 
Section 4.1.2. As noted above, the investigator needs to evaluate the potential of increased 
exposure to nintedanib when coadministered with IMP by monitoring adverse events and 
managing them according to the guidance in the nintedanib prescribing information and the 
guidance provided in this protocol.  
Details for capture of the suspected and confirmed cases of COVID-19 based on the symptoms 
and the confirmatory test, respectively, have been provided in data entry guidance issued to the 
sites, and will be included in the CRF completion guidelines.  
All these cases, whether suspected or confirmed, should be documented in the CRF. 
Clinical studies 
GLPG1690 has been evaluated in several Phase 1 studies and in the GLPG1690-CL-202 study 
with patients. Administration of GLPG1690 was generally safe and well tolerated. In the 
GLPG1690-CL-202 study, FVC values remained stable in the majority of subjects on 
GLPG1690 600 mg q.d. (+8 mL mean change from baseline) when administered for 12 weeks 
(refer to Section 2.2.1).  
Special populations 
As there is limited clinical experience with GLPG1690 so far, the IMP should not be 
administered to subjects with severe renal impairment or with moderate to severe hepatic 
impairment. 
Refer to the IB (Edition 6, 28-Jun-2019) and any relevant updates/addenda/errata for additional 
information on the safety of the IMP. 

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4.5. 
CLINICAL STUDY POPULATION 
4.5.1. Inclusion Criteria 
Subjects who meet all of the following criteria are eligible for this clinical study: 
1. Able and willing to comply with the protocol requirements and signed the informed 
consent form (ICF) as approved by the Independent Ethics Committee (IEC)/Institutional 
Review Board (IRB), prior to any screening evaluations. 
2. Subject must be able and willing to comply with restrictions on prior and concomitant 
medication as described in Section 4.5.3.2. 
3. Male or female subject aged ≥40 years on the day of signing the ICF.  
4. Criterion modified per amendment. 
4.1 
A diagnosis of IPF within 5 years prior to the screening visit, as per applicable 
ATS/ERS/JRS/ALAT guideline at the time of diagnosis [28, 29]. 
5. Chest HRCT historically performed within 12 months prior to the screening visit and 
according to the minimum requirements for IPF diagnosis by central review based on 
subject’s HRCT only (if no LB available), or based on both HRCT and LB (with 
application of the different criteria in either situation) (see Appendix 1). If an evaluable 
HRCT <12 months prior to screening is not available, an HRCT can be performed at 
screening to determine eligibility, according to the same requirements as the historical 
HRCT.  
6. Criterion modified per amendment. 
6.1 
Subjects receiving local standard of care for the treatment of IPF, defined as either 
pirfenidone or nintedanib at a stable dose for at least two months before screening, 
and during screening; or neither pirfenidone or nintedanib (for any reason). A stable 
dose is defined as the highest dose tolerated by the subject during those two months. 
7. The extent of fibrotic changes is greater than the extent of emphysema on the most recent 
HRCT scan (investigator-determined).  
8. Meeting all of the following criteria during the screening period: 
• FVC ≥45% predicted of normal. 
• Forced expiratory volume in 1 second (FEV1)/FVC ≥0.7. 
• DLCO corrected for Hb ≥30% predicted of normal (see Appendix 2).  
9. Criterion modified per amendment. 
9.1 
In a stable condition and suitable for study participation based on the results of a 
medical history, physical examination, vital signs, 12-lead ECG, and laboratory 
evaluation. Stable condition is based on the clinical judgment of the investigator; 
co-morbidities should be treated according to the local applicable guidelines. 
Concomitant medication for chronic co-morbidities should have been stable from 
4 weeks prior to screening and during the screening period (stable defined as no 
clinically relevant change according to the investigator’s judgment). 
10. Estimated minimum life expectancy of at least 30 months for non-IPF related disease in 
the opinion of the investigator. 
11. Male subjects and female subjects of childbearing potential agree to use highly effective 
contraception/preventive exposure measures (as described in Section 4.5.3.1) from the 
time of first dose of IMP (for the male subject) or the signing of the ICF (for the female 

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subject), during the study, and until 90 days (male) or 30 days (female) after the last dose 
of IMP.  
12. Criterion modified per amendment. 
12.1 Able to walk at least 150 meters during the 6MWT at screening Visit 1; without 
having a contraindication to perform the 6MWT (see Appendix 10) or without a 
condition putting the subject at risk of falling during the test (investigator’s 
discretion). The use of a cane is allowed, the use of a stroller is not allowed at all 
for any condition. At Visit 2, for the oxygen titration test, resting SpO2 should be 
≥88% with maximum 6 L O2/minute; during the walk, SpO2 should be ≥83% with 
6 L O2/minute or ≥88% with 0, 2 or 4 L O2/minute. 
13. Able to read and complete the EQ-5D, SGRQ, LCQ, K-BILD questionnaire, and VAS by 
themselves.  
14. Able to understand the importance of adherence, and willing to comply to study treatment, 
study procedures and requirements as per study protocol, including the concomitant 
medication restrictions (described in Section 4.5.3.2). 
4.5.2. Exclusion Criteria 
Subjects meeting one or more of the following criteria cannot be selected for this clinical study: 
1. Investigator or other study staff or relative thereof who is directly involved in the conduct 
of the study. 
2. Any clinical condition or other condition or circumstance that, in the opinion of the 
investigator, may make a subject unsuitable for inclusion or unlikely or unable to 
complete the study or comply with study procedures and requirements. 
3. Previous participation in a clinical study with GLPG1690 (active or placebo). 
4. Known hypersensitivity to any of the IMP ingredients or a history of a significant allergic 
reaction to any drug as determined by the investigator (e.g. anaphylaxis requiring 
hospitalization). 
5. Criterion modified per amendment. 
5.2 
A current immunosuppressive condition (e.g. human immunodeficiency virus 
[HIV] infection, congenital, acquired, medication-induced). Subjects treated with 
stable doses of immunosuppressive medications for reasons other than IPF are 
allowed to participate in the study on a case-by-case basis based on discussion 
with the sponsor’s medical monitor. 
6. Criterion modified per amendment. 
6.1 
Positive blood testing for hepatitis B surface antigen (HBS Ag) or hepatitis C virus 
(antibody, confirmed by hepatitis C virus (HCV) RNA positivity). Note: Subjects 
with a resolved hepatitis A at least 3 months prior to screening can be screened. 
7. History of malignancy within the past 5 years (except for carcinoma in situ of the uterine 
cervix, basal cell carcinoma of the skin that has been treated with no evidence of 
recurrence, prostate cancer that has been medically managed through active surveillance 
or watchful waiting, squamous cell carcinoma of the skin if fully resected, and Ductal 
Carcinoma In Situ). 
8. Criterion modified per amendment. 
8.1 
Clinically significant abnormalities detected on ECG of either rhythm or 
conduction, a QTcF >450 ms, or a known long QT syndrome. Patients with 

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implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time 
may be enrolled in the study based upon investigator judgment following 
cardiologist consultation if deemed necessary, and only after discussion with the 
medical monitor.  
9. Currently taking medication known to be a substrate mainly metabolized by CYP2C8 
(see Appendix 3). 
10. Currently taking medication known to be strong inducers of CYP3A4 (Appendix 4), and 
also including St-John’s Wort. 
11. Currently taking medication known to be strong inhibitors of CYP3A4 (Appendix 5). 
12. Currently taking medication known to be potent inducers of P-gp (Appendix 4). 
13. Currently taking medication known to be potent inhibitors of P-gp (Appendix 6). 
14. Criterion modified per amendment. 
14.1 Acute IPF exacerbation within 6 months prior to screening and/or during the 
screening period. The definition of an acute IPF exacerbation is as follows:  
Previous or concurrent diagnosis of IPF; Acute worsening or development of 
dyspnea typically < 1 month duration; Computed tomography with new bilateral 
ground-glass opacity and/or consolidation superimposed on a background pattern 
consistent with usual interstitial pneumonia pattern and deterioration not fully 
explained by cardiac failure or fluid overload (see Appendix 11).  
15. Criterion modified per amendment. 
15.1 Lower respiratory tract infection requiring treatment within 4 weeks prior to 
screening and/or during the screening period. 
16. Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis and 
amyloidosis), exposures (e.g. radiation, silica, asbestos, and coal dust), or drugs 
(e.g. amiodarone). 
17. History of lung volume reduction surgery or lung transplant. Note: being on a transplant 
list is allowed.  
18. Diagnosis of severe pulmonary hypertension (investigator-determined). 
19. Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months 
prior to screening or during the screening period (e.g. acute coronary disease, heart 
failure, and stroke).  
20. Criterion modified per amendment. 
20.1 Had gastric perforation within 3 months prior to screening or during screening, 
and/or underwent major surgery within 3 months prior to screening, during 
screening or have major surgery planned during the study period. 
21. Criterion modified per amendment. 
21.1 A history of being admitted to an institution under an administrative or court order, 
if applicable by local legislation, as well as any subjects falling into any of the 
categories of persons listed by applicable law and regulations as protected persons 
for which participation in a study is prohibited or subject to restrictions. 
22. Criterion modified per amendment. 
22.2 History of nintedanib-related increase in ALT and/or AST of >5xULN and 
increased susceptibility to elevated LFT; moderate to severe hepatic impairment 
(Child-Pugh B or C); and/or abnormal LFT at screening, defined as AST, and/or 

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ALT, and/or total bilirubin ≥1.5xULN, and/or GGT ≥3xULN. Retesting is allowed 
once for abnormal LFT. 
23. Abnormal renal function defined as estimated creatinine clearance, calculated according 
to Cockcroft-Gault calculation (CCr) <30 mL/min. Retesting is allowed once. 
24. Hb level <10 g/dL. Retesting is allowed once. 
25. Criterion modified per amendment. 
25.1 Concurrent participation in another interventional drug, device, or biological 
investigational research study, or use of an investigational agent within 5 half-lives 
of the agent (or within 8 weeks when half-life is unknown, or within 6 months if 
the investigational agent is an antibody) prior to screening is not allowed.  
26. Use of any of the following therapies within 4 weeks prior to screening and during the 
screening period, or planned during the study: warfarin, imatinib, ambrisentan, 
azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, sildenafil 
(except for occasional use), prednisone at steady dose >10 mg/day or equivalent. 
27. Current alcohol or substance abuse in the opinion of the investigator. 
28. Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study 
treatment or within 30 days after the last dose of IMP. 
29. Clinical laboratory test suggestive of cholestasis with total serum bile acid levels 
>3xULN. 
4.5.3. Prohibition and Restrictions 
4.5.3.1. 
Precautions for Sexual Intercourse 
Highly effective contraceptive measures for both males and females of childbearing potential 
must be documented in the source documents. 
4.5.3.1.1. 
Female Subjects 
In line with the Heads of Medicines Agencies (HMA)’s Clinical Trial Facilitation Group 
(CTFG) recommendation [3], female subjects are considered of non-childbearing potential if 
they meet one of the following criteria: 
− 
No menses for 12 or more months without an alternative medical cause. A high 
follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to 
confirm a postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient. 
− 
Permanently surgically sterile (bilateral oophorectomy [i.e. surgical removal of ovaries], 
bilateral salpingectomy, or hysterectomy [i.e. surgical removal of uterus]). 

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All other female subjects are considered to be of childbearing potential and are required to have 
a negative serum pregnancy test before treatment. They must use one of the following highly 
effective methods of birth control from the time of signing of the ICF, during the clinical study, 
and for at least 30 days after the last dose of IMP:  
− 
Combined (estrogen- and progesterone-containing) (oral, intravaginal, transdermal) 
hormonal contraception associated with inhibition of ovulation plus a barrier method1. 
− 
Progesterone-only hormonal (oral, injectable, implantable) contraception associated with 
inhibition of ovulation plus a barrier method1.  
− 
Intrauterine device.  
− 
Intrauterine hormone-releasing system. 
− 
Bilateral tubal occlusion. 
− 
Sexual abstinence defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the study treatments. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the clinical study and the preferred and 
usual lifestyle of the subject. 
Periodic abstinence (e.g. calendar, symptothermal, post-ovulation methods), declaration of 
abstinence for the duration of a clinical study, withdrawal, spermicides only, and lactational 
amenorrhea method are not acceptable as methods of contraception.  
In case a woman of childbearing potential has a vasectomized partner, provided that partner is 
the sole sexual partner of the participant and that the vasectomized partner has received medical 
assessment of surgical success, then she is not required to use an additional form of 
contraception. 
Within these limits, the specific forms of contraception employed are left to the discretion of 
the subject, the investigator, and/or the subject’s physician.  
Female subjects of childbearing potential will be requested to do a monthly urine pregnancy 
test during the study. The monthly pregnancy test outcome must be documented on the subject 
diary card and at the next visit in the source and case report form (CRF). In case of a positive 
urine pregnancy test at home, the subject should immediately contact the clinical study center 
and the investigator must report this immediately, and under no circumstances later than 
24 hours after being made aware.  
The safety of GLPG1690 during breastfeeding is unknown. Women who are nursing are not 
allowed to take part in this clinical study. 
Pregnant women or women planning to become pregnant during the study are not allowed to 
take part in this study. 
4.5.3.1.2. 
Male Subjects 
Men should be advised not to father a child while receiving treatment and must use effective 
contraception during and up to 90 days after treatment. Male subjects intending to father a child, 
should discontinue treatment with IMP and wait for at least 90 days before stopping the 
contraceptive measures detailed in this section. 
                                                     
1 As there are no current data available regarding potential interactions between IMP and hormonal contraceptives, 
female subjects who use hormonal contraception should supplement this with a barrier method (preferably male 
condom). 

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Non-vasectomized male subjects with female partners of childbearing potential must be willing 
to use a condom from the time of the first dose of IMP, during the clinical study, and for at least 
90 days after the last dose of IMP in addition to having their female partner use one of the 
following forms of contraception: 
− 
Combined (estrogen- and progesterone-containing) (oral, intravaginal, transdermal) 
hormonal contraception associated with inhibition of ovulation.  
− 
Progesterone-only hormonal (oral, injectable, implantable) contraception associated with 
inhibition of ovulation.  
− 
Intrauterine device.  
− 
Intrauterine hormone-releasing system. 
Sexual abstinence defined as refraining from heterosexual intercourse during the entire period 
of risk associated with the study treatments is considered a highly effective contraceptive 
measure. The reliability of sexual abstinence needs to be evaluated in relation to the duration 
of the clinical study and the preferred and usual lifestyle of the subject. 
Periodic abstinence (e.g. calendar, symptothermal, post-ovulation methods), declaration of 
abstinence for the duration of a clinical study, withdrawal, spermicides only, and lactational 
amenorrhea method are not acceptable methods of contraception.  
In a case where the female partner of a male subject has undergone documented surgical 
sterilization that was performed more than 1 year before screening, then the subject is not 
required to use an additional form of contraception.  
Vasectomized male subjects with female partners of childbearing potential are not required to 
use an additional form of contraception, provided that surgical sterilization has been successful 
(documented azoospermia by semen analysis). 
Male subjects with a pregnant or breastfeeding partner should use a condom to prevent exposure 
through seminal fluid. 
No sperm donation is allowed from the first dose of the IMP until 90 days after the last dose. 
4.5.3.2. 
Prior and Concomitant Medications 
Prior therapy 
Prior therapy taken up to 12 weeks prior to and during the screening period, and pirfenidone 
and nintedanib taken any time prior to and during the screening period will be recorded after 
signing of the ICF, at Visit 1. 
Concomitant therapy 
Should any treatment other than the IMP be used during the course of the study, the name of 
the therapy, the dosage, the route, the reason for therapy, and the start and stop dates of 
administration must be recorded until the last visit. For subjects receiving oxygen, the volume 
administered per minute will also be recorded at each visit. 
Concomitant therapies taken for the long-term treatment of pre-existing conditions can continue 
during the study, provided they are in accordance with the in- and exclusion criteria (see 
Sections 4.5.1 and 4.5.2, respectively). It is required that the use of these medications should 

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have been stable from 4 weeks prior to screening and during the screening period (at the 
investigator’s discretion). For nintedanib and pirfenidone, subjects need to have received a 
stable dose for at least two months prior to screening and during screening; stable being defined 
as the highest dose tolerated by the subject during those two months.  
In case additional concomitant medication needs to be administered or dose adjustments for 
pre-existing conditions need to be performed during the study, the benefit-risk to the subject 
should be carefully assessed and consideration given to the timing of any necessary introduction 
of new medications. 
The following therapies are prohibited during the course of the study and within 4 weeks prior 
to screening, because of lack of benefit or suggestion of harm in IPF: warfarin, imatinib, 
ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, 
sildenafil (except occasional use), prednisone at steady dose >10 mg/day or equivalent. 
If during the study, the subject’s condition necessitates the use of one of the above mentioned 
medications (excluding high-dose steroids), the use of IMP should be interrupted until 
resolution or stabilization of this condition, preferably after consultation with the CRO medical 
monitor (as per study contact list) or sponsor’s study physician (if the former is not available).  
Precautions with concomitant medication known to prolong the QT interval 
The use of medication known to prolong QT interval during the study needs to be based on a 
benefit-risk evaluation by the investigator, e.g. in the case of atrial fibrillation. In certain other 
situations (e.g. the initiation of macrolides or fluoroquinolones in case of a lower respiratory 
tract infection), when the benefit-risk evaluation necessitates the administration of medication 
known to or potentially prolonging QT, IMP can be interrupted as evaluated by the investigator 
after clinical assessment of the subject’s profile, including the baseline QTcF and how this has 
changed over time for this specific subject. If the investigator elects to continue IMP, additional 
monitoring will be performed as per investigator’s judgment. A non-exhaustive list of 
medication known to prolong QT interval is provided in Appendix 7. 
Precautions with other concomitant medications 
At dose levels of 600 mg q.d., GLPG1690 has the potential to influence substantially the 
metabolism of substrates of CYP2C8 and to potentially be influenced by known strong 
CYP3A4/potent P-gp inducers/inhibitors. 
• GLPG1690 demonstrated a strong time-dependent inhibition potential against 
CYP2C8-mediated metabolism. Consequently, GLPG1690 should not be used 
concomitantly with medications primarily or solely metabolized via CYP2C8 (see 
Appendix 3). For other medications involving part of their metabolism pathway via 
CYP2C8, caution should be applied on a case-by-case basis taking into consideration 
the benefit/risk ratio. Statins such as fluvastatin and pitavastatin are metabolized to some 
degree by CYP2C8, and need to be used with caution. Other statins such as simvastatin, 
lovastatin, and atorvastatin are theoretically less metabolized by CYP2C8. Monitoring 
of LFTs and creatine kinase is implemented during the study, and guidance to the 
subject aligned with guidance for statins in clinical practice is therefore strongly 
recommended. Loperamide is also a substrate of CYP2C8, and special caution should 
be applied in alignment with clinical practice. 

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• GLPG1690 is a substrate of CYP3A4 and P-gp, and could therefore be influenced by 
their respective inhibitors and inducers. GLPG1690 exposure is reduced up to 90% by 
the strong CYP3A4/potent P-gp inducer rifampin. As a consequence, strong inducers of 
CYP3A4 and/or P-gp are part of the exclusion criteria and should be avoided during the 
study to ensure proper exposure to GLPG1690 (see Appendix 4). For inhibition, strong 
CYP3A4 and dual strong 3A4 and potent P-gp inhibitors have shown that GLPG1690 
exposure increased by 3 to 4 fold when coadministered therefore use of known strong 
CYP3A4 inhibitors and potent P-gp inhibitors is prohibited during the study (see 
Appendix 5 and Appendix 6). Antibiotics from the macrolide therapeutic class are 
excluded, unless they are used for the short-term treatment of a lower respiratory tract 
infection with interruption of IMP, which is restarted as soon as possible after the 
completion of the treatment with macrolides. 
It is highly recommended that the CRO medical monitor (as per study contact list) or sponsor’s 
study physician (if the former is not available) are consulted before the initiation of medication 
known to prolong QT interval, to be a CYP2C8 substrate, or to inhibit or induce P-gp/CYP3A4. 
In certain situations, when the benefit-risk evaluation necessitates the administration of 
medication excluded from use during the study, IMP should be interrupted and restarted as soon 
as possible.  
As a rule, inclusion of subjects with stable chronic illness on stable medications which are 
metabolized/transported by the abovementioned CYP/transporter enzymes should be decided 
on a case-by-case basis if not excluded or prohibited, taking into account the medical history, 
concomitant medication of the subject, the therapeutic index of the medication, and safety 
profile.  
As indicated in the study contact list, the CRO medical monitor should be contacted, or the 
sponsor’s study physician in case the former is not available (when deemed necessary by the 
investigator), specifically for medication with a narrow therapeutic index and/or a risk of 
(un)predictable AEs.  
Rescue medication  
If the subject shows a worsening of his/her IPF disease condition (e.g. acute IPF exacerbation), 
all treatment options are allowed at the investigator’s discretion. The decision to continue the 
IMP should be taken on a case-by-case basis by the investigator and in case of doubt can be 
discussed with the CRO medical monitor (as per study contact list) or sponsor’s study physician 
(if the former is not available).  
4.5.3.3. 
Food and Beverage Restrictions 
The use of St-John’s Wort, a strong CYP3A4 inducer, is prohibited during the study. 
Double-strength grapefruit juice is potentially a potent CYP3A4 inhibitor and therefore should 
be avoided during the study. 
4.5.3.4. 
Other Prohibitions and Restrictions 
Not applicable. 

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4.5.4. Treatment Discontinuation, Subject Withdrawal, and Study 
Termination 
All subjects will continue on IMP until the last subject reaches 52 weeks into the study 
(Visit 12) (for details, please refer to Section 4.1 and to Section  6.1 “Specific study visits when 
the last subject reaches 52 weeks into the study (Visit 12)”).  
Subjects will be informed prior to clinical study entry that they are allowed to withdraw from 
the clinical study. At any time and for any reason, a subject’s participation in the clinical study 
may terminate at his/her request, without prejudice to his/her future medical care. The subject 
will be encouraged to share the reason(s) for withdrawal so this can be documented in the source 
documents.  
Subjects who choose to withdraw from study participation will be asked if they are prepared to 
complete a last visit. In this case, either the EoST or EoSA visit should be performed. The 
subjects’ vital status information will be collected at the time of the EoST/EoSA visit of the last 
subject who reaches 52 weeks in the study (Visit 12), according to national, ethical, and 
regulatory guidelines, and as per the subjects’ confirmation in the signed main ICF. If the 
subject initially confirmed no vital status information to be collected, but reconsiders at the time 
of actual withdrawal of consent, the subject has to re-consent for this in writing. 
Subjects who withdraw from the clinical study without contacting the clinical study center (lost 
to follow-up) should be contacted by the clinical study center so that their health status can be 
assessed and documented in the source documents. The clinical study center should make every 
effort to understand whether the subject is alive, including checking the medical records, 
contacting general practitioner or relatives, if necessary. All attempts must be documented in 
the source documents.  
Subjects who discontinue IMP early (ETD), with the exception of patients who withdraw 
consent and patients lost to follow-up, will be encouraged to complete all following visits and 
evaluations as originally planned per protocol (see below, “Procedures in case of early treatment 
discontinuation (ETD)”). 
The sponsor has the right to terminate the clinical study at any time in case of safety concerns 
or if special circumstances concerning the IMP or the company itself occur, making further 
treatment of subjects impossible. In this event, the subjects, investigator(s), and relevant 
authorities will be informed of the reason for clinical study termination. 
Discontinuation of IMP 
Treatment with IMP will be discontinued by the investigator (preferably after discussion with 
the CRO medical monitor, who may consult and must inform the sponsor’s study physician) 
for any of the following reasons: 
− 
Life-threatening AE or a serious adverse event (SAE) that places the subject at immediate 
risk. 
− 
Confirmed pregnancy: if a subject becomes pregnant during the study (to be confirmed 
by local serum pregnancy test; central measurement will also be performed), the IMP has 
to be stopped immediately and the subject has to be followed up until birth or otherwise 
termination of pregnancy. The subject needs to be unblinded immediately and repeat 
counseling on birth defect risk must be offered in case she was on active drug. 

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− 
Arrhythmia or conduction abnormality, including but not limited to prolonged QTcF, 
where the severity is categorized as Common Terminology Criteria for Adverse Events 
(CTCAE) Grade 3 or higher. 
− 
An increase for QTcF of >60 ms from baseline (Visit 3) or QTcF >500 ms at any ECG 
recording (any recording of triplicate ECG or single ECG) needs to be confirmed by an 
ECG recording as soon as possible from the original abnormal recording at the same visit.  
If the abnormal recording is discovered after the visit, the recording should be confirmed 
as soon as possible. In case of an abnormal ECG on both of these two recordings is 
confirmed, the investigator needs to send an immediate alert to the central reader for 
confirmation as well as to the CRO medical monitor (as per study contact list) or 
sponsor’s study physician (if the former is not available). If the ECG abnormality is 
before IMP intake, IMP administration will be withheld until the central reader has 
reviewed the ECG registration. In case of confirmation of the ECG abnormality, IMP will 
be discontinued for this subject. Only in case a response of the central reader is not 
available within the timeframe of the visit, the investigator can proceed to discontinue the 
treatment of the subject.  
If a normal QTcF is reported during the visit, but the central cardiologist reports it as 
abnormal (any of the two criteria above), then the IMP should be discontinued as soon as 
possible. 
− 
Increase in LFTs (also see Appendix 9): 
• 
At Visit 3 immediately after randomization: test results will only be available after 
the first IMP intake. If the subject meets the exclusion criteria for AST, ALT, total 
bilirubin, and GGT, then treatment with IMP will be discontinued. 
• 
Any other visit: 
• 
AST or ALT ≥8xULN 
• 
AST or ALT ≥3xULN with signs of severe liver damage (i.e. with the 
appearance of fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash and/or eosinophilia [>5%], and/or total bilirubin 
≥1.5xULN or INR >1.5) 
• 
AST or ALT ≥3xULN for more than 2 weeks 
• 
AST or ALT ≥3xULN during re-escalation 
− 
Clinical laboratory test suggestive of cholestasis with total serum bile acid levels 
>3xULN on a sample taken in fasted state (at least 8 hours fasted). If the routine random 
or postprandial total serum bile acid sample is >3xULN, then the subject should have a 
fasted sample taken within 1 to 5 days. The results of this test will determine whether the 
subject should discontinue IMP or not. 
− 
Chronic (defined as: anticipated to be administered for more than 3 months) use of 
concomitant medication not permitted during the study. 
− 
Closing of the study by the sponsor or regulatory authorities.  
Wish of the subject to stop taking IMP. 
For a subject having: 
• 
AST or ALT ≥8xULN 
• 
AST or ALT ≥3xULN with signs of severe liver damage (i.e. with the appearance of 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or 
eosinophilia [>5%], and/or total bilirubin ≥1.5xULN or INR >1.5) 

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the following steps will need to be performed by the investigator.  
− 
The site should immediately contact the subject and require the subject to discontinue 
IMP immediately. The subject should be asked to return to the site within a 48-hour 
window from awareness of the result.  
− 
An assessment of other concomitant medications and SoC should be made. The 
investigator should consider whether is in the best interest of the subject to interrupt 
concomitant medications and SOC treatment.  
− 
A detailed history including relevant information on alcohol use, recreational drug use, 
supplement consumption, any herbal remedies, family history, sexual history, travel 
history, history of contact with a jaundiced subject, surgery, occupational history, blood 
transfusion, history of liver or allergic disease, and any other potential causes of a liver 
insult should be collected.  
− 
A detailed assessment of the subject’s clinical condition and repeat laboratory tests for 
LFT, including albumin, creatine kinase, total bilirubin (direct and indirect), GGT, INR 
and alkaline phosphatase should be done  
− 
Further testing for Hepatitis A, B, and C, and for autoimmune hepatitis should be done. 
Other causes of viral hepatitis (CMV or EBV etc) should be excluded.  Liver imaging 
should be considered.  
− 
Referral to a hepatologist or gastroenterologist should be considered. 
− 
All these cases should be reported as SAEs.  
 
Every effort should be made to keep subjects in the study and on treatment. However, the 
investigator can consider stopping treatment with IMP, preferably after consultation with the 
CRO medical monitor (as per study contact list) or sponsor’s study physician (if the former is 
not available), in case of concerns about the subject’s safety, major protocol noncompliance, 
serious or severe AEs or worsening of the disease condition, which in the investigator’s opinion 
needs an alternative treatment approach not being covered in the clinical study (e.g. rescue 
medication).  
− 
At Visit 3: as the blood sample is taken before first IMP intake and the results are only 
available after first IMP intake, the investigator needs to justify continuation of IMP in 
writing for abnormal results (based on the exclusion criteria) for: 
• 
Creatinine clearance 
• 
Hb 
The reason(s) for stopping the IMP will be documented in the CRF.  
Procedures in case of early treatment discontinuation (ETD) 
Subjects who discontinue IMP early will complete an ETD visit. They will be encouraged to 
complete all following visits and evaluations as originally planned per protocol (i.e. including 
an EoSA visit when the last subject reaches 52 weeks into the study [Visit 12]). The subject 
will be informed about this at signing of the ICF. 
In particular, the subject will be requested if at all possible to attend:  
− 
the first scheduled visit after their Early Treatment Discontinuation (ETD)  
− 
The Week 26 visit (if not done before IMP discontinuation) 

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− 
the Week 52 visit (if not done before IMP discontinuation) 
− 
after Week 52, visits every 24 weeks up to EoSA, as described in Section 6.11.2 
An ETD visit will be scheduled as soon as possible from the day of early discontinuation of 
IMP. In case the subject discontinues IMP on a scheduled visit, that visit should be completed 
and, in addition, the assessments from the ETD visit that are not part of the scheduled visit 
should be performed. If the subject is not able or not willing to come back for an ETD visit, the 
investigator will contact the subject by phone, and if the subject has agreed to this in the ICF, 
may consult the subject’s medical record and/or contact the subject’s general practitioner or 
relatives, if necessary, to obtain the needed information.  
4.6. 
MEASURES TO MINIMIZE BIAS 
4.6.1. Randomization 
At screening, subjects will be assigned a subject identification number. When a subject is 
confirmed to be eligible for the clinical study, he/she will be randomized.  
A total of approximately 750 subjects will be randomized in a 1:1:1 ratio to receive 
GLPG1690 600 mg q.d., GLPG1690 200 mg q.d., or matching placebo for at least 52 weeks. 
Allocation of each subject to a given treatment will be described in a randomization list prepared 
by a CRO. This randomization list will be stratified in a balanced manner for background local 
standard of care for treatment of IPF (nintedanib, pirfenidone, or neither). Recruitment may 
stop earlier in one or more strata to maintain the balance as indicated, while the other strata(s) 
continue to recruit. Upon qualification for the study, allocation of each subject to a given 
treatment will be done using a centralized electronic system (interactive web response system 
[IWRS]) with permuted blocks. 
For each subject at each visit, the clinical study center will contact the IWRS for the appropriate 
treatment number to be assigned. Each medication kit will contain the relevant IMP for the 
period until the next visit. 
Subjects and study personnel will be blinded to the treatment assignment. Additional details on 
blinding and unblinding are provided in Section 4.6.2. 
4.6.2. Blinding and Unblinding 
This is a randomized, double-blind clinical study. The subject and the entire clinical study team, 
including the investigators, clinical study coordinators, and sponsor personnel are blinded to 
treatment assignment, except for situations described in the last paragraph of this section. 
Blinded and packaged medication will be provided to the clinical study center. All IMP 
formulations will be packaged in the proper proportion to assure desired dosages and 
maintenance of the blinding. In case of down-titration, interruption, or re-escalation, a sham 
dose level is available for the treatment allocation arm of GLPG1690 200 mg in order to ensure 
the same number of steps as the other treatment allocation arms and to ensure blinding (for 
details, refer to Sections 4.1 and 5.2). The different steps are blinded for treatment allocation 
but not for dose level. 
The blind can be broken only if the investigator deems it necessary for the safety of a subject. 
The investigator is encouraged to discuss considerations to break the blind with the CRO 

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medical monitor (as per study contact list) or the sponsor’s study physician (in case the former 
is not available), whenever possible and where the situation allows. However, the responsibility 
to break the treatment code in emergency situations resides solely with the investigator. The 
investigator is not required to discuss unblinding beforehand if he/she feels rapid emergency 
unblinding is necessary, but is required to inform the CRO medical monitor and sponsor in a 
timely fashion after unblinding has occurred. 
The blind can be broken by the investigator via the IWRS. If the blind is broken for any reason 
during the course of the study, the moment on which the subject’s data were unblinded and all 
other relevant information will be documented by the clinical study center, the CRO, and other 
sponsor designees, as appropriate. The reason for breaking the blind will be indicated and 
justified in the source documentation and in the CRF. 
Code-break information (via IWRS vendor/randomization list) will be provided to the 
bioanalytical laboratory responsible for plasma drug determination sample analysis and to the 
sponsor pharmacovigilance lead for SAE reporting purposes. The IDMC will have access to 
unblinded data (for details, refer to Section 8.1). 
5. 
INVESTIGATIONAL MEDICINAL PRODUCT 
5.1. 
IDENTITY OF THE INVESTIGATIONAL MEDICINAL 
PRODUCT 
The IMPs (GLPG1690 and placebo) will be supplied to the clinical study center, by and under 
the responsibility of the sponsor, who will also provide the investigator with European Union 
Qualified Person release documents. 
GLPG1690 will be provided as film-coated tablets for oral use, containing 100 mg or 
200 mg G451990 each (G451990 is the compound code for GLPG1690). The placebo will be 
provided as matching film-coated tablets for oral use. The GLPG1690 100-mg tablets and the 
placebo tablets matching the GLPG1690 100-mg tablets will be smaller than the 
GLPG1690 200-mg tablets and the placebo tablets matching the GLPG1690 200-mg tablets. 
A full list of excipients used in the film-coated tablet formulation is available in the IB (Edition 
6, 28-Jun-2019) and any relevant updates/addenda/errata.  
5.2. 
DOSAGE AND ADMINISTRATION 
The following doses will be tested; three tablets will be provided per dose (high [original] dose 
level): 
− 
GLPG1690 600 mg q.d. (as three GLPG1690 200-mg tablets) 
− 
GLPG1690 200 mg q.d. (as one GLPG1690 200-mg tablet and two placebo tablets, 
matching the GLPG1690 200-mg tablet) 
− 
placebo q.d. (as three placebo tablets, matching the GLPG1690 200-mg tablet) 
The following doses will be provided for down-titration and re-escalation; two tablets will be 
provided per dose: 
Low (reduced) dose level: 

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− 
GLPG1690 200 mg q.d. (as one GLPG1690 200-mg tablet and one placebo tablet, 
matching the GLPG1690 100-mg tablet) 
− 
GLPG1690 100 mg q.d. (as one GLPG1690 100-mg tablet and one placebo tablet, 
matching the GLPG1690 200-mg tablet)  
− 
placebo q.d. (as one placebo tablet, matching the GLPG1690 200-mg tablet and one 
placebo tablet, matching the GLPG1690 100-mg tablet) 
Intermediate (reduced) dose level: 
− 
GLPG1690 400 mg q.d. (as two GLPG1690 200-mg tablets) 
− 
GLPG1690 200 mg q.d. (as one GLPG1690 200-mg tablet and one placebo tablet, 
matching the GLPG1690 200-mg tablet) 
− 
placebo q.d. (as two placebo tablets, matching the GLPG1690 200-mg tablet)  
Refer to Figure 2 in Section 4.1.2 for an overview of number of tablets to be taken per dose 
level. 
Subjects will be instructed to swallow the tablets as a whole with a glass of water and to not 
chew the drug prior to swallowing. On visit days, subjects will be instructed to take their IMP 
at the clinical study center, to allow for predose (i.e. before IMP intake) assessments to be 
completed.  
At Visits 3, 9, and 12, the subject will be asked to take pirfenidone or nintedanib (if applicable) 
at the clinical study center.  
If a subject misses a dose (e.g. because he/she forgot to take the medication), he/she should take 
the missed dose within 12 hours after the planned intake time and within 2 hours of food intake. 
If the IMP is not taken within 12 hours after the planned time, the missed dose should be 
skipped. 
The IMP is to be taken q.d. at the same time every day with food (e.g. breakfast, small meal, or 
a snack) or after food intake, taking into account the timing of the planned visits, with a 
maximum of 2 hours between the food intake and IMP intake.  
For subjects who are taking nintedanib as standard of care medication at screening or 
randomization or who start nintedanib during the study, it is recommended to take the IMP at 
or after lunch (approximately 4 hours after nintedanib morning intake).  
5.3. 
PACKAGING, LABELING, AND DISTRIBUTION 
The film-coated tablet for oral use will be packaged in blisters.  
All manufacturing, packaging, and labeling operations will be performed according to Good 
Manufacturing Practices (GMP) for Medicinal Products and the relevant regulatory 
requirements. 
Each medication kit will be identified with a unique kit number. A multiple of kits will be 
provided to the subject at each visit, providing the subject with sufficient tablets to cover the 
period until the next scheduled visit.  
The distribution to the clinical study center will only occur after all required documentation is 
obtained including clinical study approval by Competent Authorities and the IECs/IRBs, 

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documentation on which the assessment of the investigator’s qualifications was based 
(e.g. curriculum vitae), and the signed and dated study agreement and financial agreement. The 
IMP is to be dispensed according to the protocol. 
In case study subjects cannot attend site visits, due to any COVID-19-related reason, direct-to-
patient (DTP) shipment of IMP has been implemented and can be used to ensure the dosing 
regimen per protocol requirement can be maintained. DTP should only be used in case of 
emergency where on-site IMP dispensing is not possible, and if allowed per local regulations. 
Local guidelines must be followed and regulatory approval or notification of authorities may 
be required. The DTP process used will be reviewed and approved by the sponsor. If the DTP 
shipments originate from the investigational site(s), their coordination will be ensured by the 
investigational site(s) in collaboration with the CRO to ensure clinical integrity without the 
involvement of the sponsor. Detailed guidance on the shipment has been provided to the sites 
in COVID-19 guidance documents. Consent of the subjects to receive IMP at home is required 
prior to the shipment of IMP, and should be documented in the source data. Return shipment of 
unused IMP from the subjects to the site may be implemented if allowed per local regulations. 
5.4. 
STORAGE 
Clinical study centers are to store all drug supplies in a secure, locked area with limited access 
below 30°C, protected from light, until dispensed. Clinical study centers will be required to 
monitor the storage temperature by using at least a calibrated minimum-maximum 
temperature-recording device and to keep a minimum to maximum temperature log, which must 
be completed each working day in order to establish a record of compliance with these storage 
conditions. The investigator will instruct subjects on how the IMP should be stored at home. 
5.5. 
TREATMENT COMPLIANCE AND DRUG ACCOUNTABILITY 
For each dose taken at home, the date and number of tablets taken should be recorded on the 
subject diary card (see Section 6.4 for additional information). A new diary card will be 
provided together with each new medication kit. Any interruption or change in treatment 
(together with the reason for change) should be documented on the subject diary card. 
The investigator or designated clinical study personnel will maintain a log of the total amount 
of IMP received at the clinical study center, amount dispensed to the subject, and the amount 
of IMP returned by the subject to the clinical study center. IMP supplies for each subject will 
be inventoried and accounted for throughout the clinical study. These records will be checked 
against the inventory by the study monitor on a regular basis. All clinical supplies will be stored 
in locked facilities. 
Subjects will return any unused IMP and empty IMP packages at each study visit. Missed doses 
should be discussed to try to ascertain the reason(s). Every effort should be made to ensure 
proper subject dosing. Subjects with poor compliance will be re-trained by the clinical study 
center. 
Treatment compliance will be assessed by the investigator or designee. At each visit, clinical 
study center staff will review treatment compliance by assessing the number of returned IMP.  

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6. 
CLINICAL STUDY ASSESSMENTS 
Every effort should be made to ensure that protocol-required tests and procedures are completed 
as described in the Schedule of Activities (see Section 6.11). To avoid inter-observer variability, 
a reasonable effort should be made to ensure that all safety and efficacy evaluations are 
completed by the same individual who made the initial baseline determinations. 
For subjects who, for any COVID-19-related reason, cannot perform study procedures, 
extended visit windows, the possibility to conduct phone/televisits followed by home (or other 
remote location) visits, and alternative assessment procedures are detailed in Section 6.1.1. 
6.1. 
TIMING OF ASSESSMENTS 
The study assessments will be undertaken at time points as specified in the Schedule of 
Activities in Section 6.11. A window of ±2 days is allowed for Visits 4 and 5, ±4 days for 
Visits 6 to 12, and ±7 days for all visits after Visit 12.  
The ICF needs to be signed before any study procedure, including screening procedure, is 
carried out. The ICF signature is the start of the 28-day screening period and will be used as the 
date of Visit 1. 
Please note that the both Visit 1 and Visit 2 can have a duration of more than one day to 
accommodate all screening assessments. 
Visit 1: The preferred sequence of study assessments will be as follows (urine analysis can be 
done at any stage during the visit): 
1. Only for subjects taking nintedanib: the time of nintedanib intake will be recorded. 
2. In- and exclusion criteria, demographics, medical history, alcohol consumption, and 
smoking habits 
3. EQ-5D, SGRQ, LCQ, K-BILD, VAS Cough and Urge to Cough questionnaires 
4. ECG (triplicate)* 
5. 
 
6. Spirometry** (Spirometry should not be repeated until notification from the central 
reader is received) 
7. DLCO 
8. Assessment of (S)AE(s) and prior and concomitant medication 
9. Physical examination and vital signs (supine heart rate, respiratory rate, systolic and 
diastolic blood pressure [SBP and DBP], and body temperature)  
10. Blood sampling for safety, FSH (if applicable), serum pregnancy test, and clinical 
laboratory tests 
11. Only for subjects taking nintedanib: blood sampling for nintedanib concentration 
assessment 2-4 hours after nintedanib intake 
12. 
 
13. 
 
14. 6MWT 
 
15. Repeat spirometry** if acceptability and repeatability criteria as defined in the 
ATS/ERS/JRS/ALAT guidelines are not met as confirmed by the central spirometry 
reader 

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16. Only for subjects taking nintedanib: blood sampling for nintedanib concentration 
assessment 5-10 hours after nintedanib intake  
*In case an indwelling catheter is used, ECGs may be recorded after blood sampling, 
provided that there is at least 30 minutes between catheter insertion and the ECG recording 
(for details, refer to Section 6.6.5). 
**Subjects using inhaled bronchodilators can do this after the confirmed spirometry 
assessment, unless clinically indicated to administer earlier. 
Note: If needed, an HRCT needs to be planned and performed during the screening period 
before Visit 2. This can be done during an unscheduled visit in the screening period. A repeat 
HRCT is only allowed to be performed once for study eligibility; if the HRCT is >12 months 
old; or if the available historic HRCT cannot be evaluated. 
As soon as possible after signing the ICF, the investigator will transmit the HRCT images and 
the LB specimens (if available) for review (for details, refer to Section 6.3 and Appendix 1). 
 
Subjects can only proceed to Visit 2 if the diagnosis of IPF is confirmed by central reading of 
the chest HRCT and (if available) LB, and if all other test results with the exception of ECG (if 
a retest is needed) allow the subject to proceed. 
Visit 2: 
1. Repeat abnormal ECG if the central reading of the Visit 1 ECG report confirms that 
QTcF does not meet eligibility criterion. 
2. Spirometry* (Spirometry should not be repeated until notification from the central 
reader is received) 
3. 
 
4. Oxygen titration test for the 6MWT 
 
5. Assessment of (S)AE(s) and concomitant medication 
6. Repeat spirometry* if acceptability and repeatability criteria as defined in the 
ATS/ERS/JRS/ALAT guidelines are not met as confirmed by the central spirometry 
reader 
7. Repeat liver function tests, creatinine clearance and Hb if needed 
8. Repeat total serum bile acid if needed on a sample taken in fasted state (at least 8 hours 
fasted) 
*Subjects using inhaled bronchodilators can do this after the confirmed spirometry 
assessment, unless clinically indicated to administer earlier. 
Subsequent visits: the preferred sequence of study assessments during the IMP intake period, 
will be as follows (please take note of assessments that may be only required at certain visits 
and refer to the Schedule of Activities for further details): 
1. Randomization via IWRS (at Visit 3 only) 
2. Urine pregnancy test (if applicable) with urine analysis 
3. EQ-5D, SGRQ, LCQ, K-BILD, VAS Cough and Urge to Cough 
4. ECG (triplicate) at Visits 3 and 4; ECG (single) for any following visit* 
 

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home visit or visit at another remote location, if feasible and available, is strongly 
recommended.  
The visit windows for Visits 5, 6, 7, 8, 10, and 11 may be increased to ±7 days and the visit 
windows for Visit 9 and Visit 12 may be increased to ±28 days.  
At each visit, the subject will continue the intake of IMP (if confirmed by the responsible 
investigator or delegate, as detailed below) and will be supplied with IMP to cover the extended 
visit windows (as described in Section 5.3). Urine pregnancy tests (if applicable) and subject 
diary cards may also be supplied to the subject’s home. 
Assessments and Activities to be performed at remote and on-site visits 
For Visit 4 and all visits thereafter, if a randomized subject is not able to attend a scheduled 
study visit on site and a phone/televisit is conducted instead, then the study assessments 
should be conducted according to the Schedule of Activities (Section 6.11) as much as 
possible, in particular for Visits 9 and 12.  
If possible and available, trained study staff or trained personnel are encouraged to carry out 
study assessments at the subject’s home or another remote location (i.e. conduct phone call 
first, then conduct home/remote location visit).  
Sites should assess risk to subjects’ safety incurred by home (or other remote location) visits 
and ensure that the staff sent to the subject’s home do not pose a risk of infection to the subject 
or vice versa. 
At the phone/televisits or home (or other remote location) visits, the investigator should collect 
information on adverse events (changes of ongoing or new events), changes in concomitant 
medications or standard of care, and enquire about ongoing IMP intake (completion of subject 
diary cards).  
At the home (or other remote location) visits, the following assessments should be performed 
(if appropriate as per Schedule of Activities, Section 6.11). If it is not possible to perform all 
assessments, every effort should be made to complete the assessments indicated with an asterisk 
(*) 
− 
physical examination (including weight) * 
− 
vital signs assessment *  
− 
safety blood sample collection for central laboratory assessment where possible or local 
laboratory assessment (if sampling conditions as per laboratory manual cannot be 
ensured) * 
− 
spirometry (using the study device) * 
− 
12-lead electrocardiogram (ECG) using the study device if possible or local assessment * 
− 
electronic clinical outcome assessment (eCOA) collection using the tablet device 
provided for the study * 
− 
  
− 
urine pregnancy test (if applicable) *  
In addition, all efforts should be made to review and collect the subject diary cards and perform 
drug accountability as well as retrieving the (un)used IMP blisters. 

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The 6MWT and DLCO can be performed if circumstances allow.  
Blood samples for PK, 
 
should not be collected at home visits. 
Additional guidance for on-site visits 
If an on-site visit for randomized subjects is feasible, all assessments for the applicable visit 
should be performed according to the Schedule of Activities (Section 6.11). However, if it is 
not possible to conduct all the assessments, then the following assessments/activities should 
be prioritized: 
− 
adverse events (changes of ongoing or new events) as well as information on 
hospitalization between visits 
− 
changes in concomitant medications or standard of care, enquiring about ongoing IMP 
intake (completion of subject diary cards), as well accountability and return of (un)used 
IMP blisters  
− 
vital signs 
− 
safety blood sample collection (for central laboratory) 
− 
spirometry and ECG (using the study devices) 
− 
eCOA (using the tablet device provided for the study) 
− 
6MWT 
− 
DLCO 
− 
Urine pregnancy test (if applicable) 
 
Guidance on continuation of IMP during the COVID-19 pandemic 
The ultimate decision to continue or interrupt IMP remains with the investigator except when 
three consecutive on-site visits have been missed and could not be replaced by 
phone/televisits, home (or other remote location) visits, and/or local lab assessments, or if the 
safety assessments could not be performed within the indicated time periods. In these cases, 
IMP should be interrupted. 
In general, the decision on IMP continuation shall depend on the investigator’s assessment of 
the subject’s clinical condition, and on the occurrence and severity of adverse events and the 
results of laboratory assessments.  
Timely (in accordance to adjusted visit windows) local safety laboratory assessment and 
home/local ECG (if possible), are strongly recommended to support the decision regarding 
continuation of IMP. If these assessments are not feasible, then the investigator should collect 
minimal assessments, such as physical condition, adverse events, and concomitant medication 
to help decide on the subject’s continuation of IMP. If only phone/televisits are possible, the 
decision to continue IMP may be based on this information.  
The following criteria should be adhered to when making the decision on continuation of IMP 
and every effort should be made to capture safety assessments to ensure IMP can be 
continued. The recommendations are specific to the study phase: 

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First phase: In case of missing visits between Visit 4 to Visit 8 (Week 2 to Week 18), safety 
assessments must be performed within an 8-week timeframe.  
Second phase: In case of missing visits between Visit 9 to Visit 12 (Week 26 to Week 52), 
safety assessments must be performed within a 12-week timeframe.  
Third phase: After Visit 12 (Week 52 to End of Study), safety assessments must be performed 
within a 16-week timeframe.  
If during any of these phases, safety assessments at home or at another remote location are not 
feasible, then at a minimum, local laboratory evaluations are needed to evaluate if the subject 
can continue IMP. ECG alternatives are to be discussed with the medical monitor. 
If IMP was interrupted, once safety assessments as specified above have been performed, the 
investigator may consider the re-start of IMP. 
6.2. 
UNSCHEDULED VISITS 
Additional visits can be performed at other time points for any safety assessment if clinically 
indicated. If local regulations allow, home visits can be performed for safety laboratory 
sampling at the investigator’s discretion. These unscheduled visits and outcomes of additional 
assessments need to be recorded in the source and, if performed before the subject’s last visit 
per protocol, also in the CRF. 
6.3. 
INITIAL SUBJECT AND DISEASE CHARACTERISTICS 
Subjects will be asked to attend the clinical study center for two screening visits, after giving 
written informed consent. 
The subject can only proceed to Visit 2 (screening visit 2) if the diagnosis of IPF is confirmed 
by central reading of the chest HRCT and by central review of the available LB, if required 
(according to the criteria in Appendix 1), and if all other test results of Visit 1 allow the subject 
to proceed.  
Retesting of individual screening assessment(s) that did not meet eligibility criteria is not 
permitted, with the following exceptions AND only in case it is still possible to randomize the 
subject within the per protocol defined screening period of 28 days: 
− 
Laboratory values for LFTs, creatinine clearance, and Hb can be retested once 
− 
Lost or invalid blood or urine samples 
Rescreening: in case of screening failure, subjects are allowed to be rescreened a maximum of 
two times, with an interval taking into account the eligibility criteria at the investigator’s 
discretion. When in doubt, the investigator can discuss rescreening with the CRO medical 
monitor (as per study contact list) or sponsor’s study physician (if the former is not available), 
on a case-by-case basis. Rescreening with the purpose to repeat a HRCT scan, is not allowed. 
If rescreened, the subject must be reconsented. The subject will be assigned a new subject 
number which will be linked to the first screening number. 

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Visit 1 
The subject’s historical HRCT and LB (if available) will only be sent for review if the minimum 
requirement of HRCT slide thickness of <1.5 mm is met. Central reading will be performed by 
two readers for the confirmation of the IPF diagnosis through: 
− 
Central review of chest HRCT, with adjudication by a third reader, if necessary 
− 
Central review of LB (if available) will be performed by one reader 
Note that both the chest HRCT and LB (if available) need to be sent to central review as soon 
as possible after signing the ICF to allow for central reading and confirmation of IPF diagnosis 
before Visit 2. Additional details are provided in Appendix 1. If needed, an HRCT needs to be 
planned and performed during the screening period before Visit 2. If an historical LB is 
available it can be used for the assessment of eligibility, but no new biopsy is required. 
For subjects on nintedanib, the time of last nintedanib intake on the day of Visit 1 will be 
verified by the investigator, and subjects will have blood samples taken for PK at Visit 1 
between 2-4 hours; and 5-10 hours after the intake of nintedanib. 
In addition, at the first screening visit, information on demographics (age, sex, and race) and 
medical history (including the multidisciplinary diagnosis of IPF at the clinical study center if 
present, the duration of disease, disease progression prior to screening [inclusion criterion], 
prior [up to 12 weeks] and concomitant medications [for IPF and other co-morbidities], 
contraception, alcohol consumption, and smoking habits) will be collected. A full physical 
examination will take place (including measurement of height and weight) and vital signs,
 
, triplicate ECG, clinical laboratory assessments (including 
serology, FSH [if applicable]), serum pregnancy test (if applicable), spirometry, DLCO, 6MWT 
, and EQ-5D, SGRQ, LCQ, K-BILD, VAS Cough and Urge to Cough 
questionnaires will be conducted to determine the subject’s eligibility for study participation. 
 
Visit 2 
At Visit 2, a second spirometry will be performed, as well as 
 and the 
oxygen titration test for the 6MWT test 
. For the oxygen titration test, resting 
SpO2 should be ≥88% with maximum 6 L O2/minute. During the walk, SpO2 should be ≥83% 
with maximum 6 L O2/minute or ≥88% with 0, 2, or 4 L O2/minute. 
During the screening period, two spirometry measurements will be performed on different visits 
(Visit 1 and Visit 2). Both measurements need to meet acceptability and repeatability criteria 
as specified by the most recent ATS/ERS/JRS/ALAT guidelines [19]. If repeat values are within 
the acceptability criteria and completed within the screening window for the two screening 
visits, the subject is eligible for the study.  
At the screening visits, central review of the spirometry will be performed as much as possible 
during the visit. In case the acceptability and repeatability criteria as specified by 
ATS/ERS/JRS/ALAT guidelines are not met, a repeat spirometry should be performed during 
the same visit, ideally within 1 hour time. 
The in- and exclusion criteria will be checked to assess eligibility for the study. All screening 
tests will be reviewed to confirm eligibility before randomization and first IMP intake. After 
the subject’s eligibility for the study has been confirmed, the subject will be randomized into 

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the study at Visit 3 before IMP intake to receive treatment with GLPG1690 600 mg q.d., 
GLPG1690 200 mg q.d., or matching placebo.  
A history of progression of disease, as defined by a relative decline in the FVC of at least 10% 
of the predicted value, during the 1 year prior to screening will be recorded, if available.  
6.4. 
SUBJECT DIARY CARD 
Subjects will be given a diary card at Visit 3 to record the following: 
− 
from Day 1 until EoST/EoSA visit, subjects will be asked to record the date of IMP intake 
and the number of tablets taken for each administration 
− 
All subjects taking nintedanib (i.e. subjects taking nintedanib at screening and 
randomization or starting nintedanib during the study) until they stop taking nintedanib, 
will be asked to indicate via tick box whether each IMP administration was approximately 
4 hours after the nintedanib morning dose 
− 
only for subjects taking nintedanib at screening and randomization until they stop taking 
nintedanib, subjects will be asked to record the time they take nintedanib at home in the 
morning on the day of Visits 4, 5, 6, 7, 8, 10, and 11, and after Visit 12 (Week 52), in the 
morning on the day of the Visits every 12 weeks until the EoST/EoSA visit 
− 
from Day 1 until EoST/EoSA visit, subjects will be asked to record changes in concomitant 
medication regimen, including new medicines not captured in medication history, use of 
bronchodilators, monthly urine pregnancy test outcome (only for WOCBP), and any other 
concomitant medication used as well as any emerging AE 
Subjects will be instructed to bring their diary card and used/unused IMP to each visit. At each 
visit, review of compliance with the diary card and subject re-training if needed, will be 
performed.  
If subjects, due to any COVID-19-related reason, cannot attend visits on site, subject diary 
cards may be sent and should be completed as has been done prior to the COVID-19 outbreak. 
All efforts should be made to review and collect the diary cards at home or other remote location 
visits (where feasible), but certainly at the next on-site visit. 
6.5. 
EFFICACY ASSESSMENTS 
6.5.1. Pulmonary Function  
6.5.1.1. 
Spirometry 
Spirometry will be performed at the clinical study center before IMP intake and repeated after 
IMP intake if indicated (see below) to assess pulmonary function at the time points specified in 
the Schedule of Activities (Section 6.11) and according to the sequence of study assessments 
described in Section 6.1.  
Clinical study centers will be provided with spirometers to be used for all study spirometry 
assessments. Spirometry devices will not be used for other purposes than this study. 
The clinical study center-based spirometry must meet the criteria for acceptability and 
repeatability as defined in the ATS/ERS/JRS/ALAT guidelines [19] for screening, and will be 
based on ATS/ERS/JRS/ALAT guidelines after randomization. 

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Pulmonary function will be measured in a standardized manner and results should be 
transmitted electronically during the visit immediately after performing the spirometry and 
evaluated by a central reader. In case the acceptability and repeatability criteria as specified by 
ATS/ERS/JRS/ALAT guidelines are not met, a repeat spirometry should be performed during 
the same visit of the screening period. After randomization, a repeat spirometry should be 
performed during the same visit, based on the ATS/ERS/JRS/ALAT guidelines [19]. 
Timing of spirometry 
The spirometry test is to be performed preferably at approximately the same time every visit. 
All spirometry evaluations should be performed pre-bronchodilator. Pre-bronchodilator 
spirometry is defined as spirometry testing performed for a subject who has: 
− 
withheld their short-acting β-agonist (e.g. albuterol) or anticholinergic (e.g. ipratropium 
bromide) for >6 hours prior to the spirometry assessment AND 
− 
withheld their long-acting bronchodilator (e.g. salmeterol, formoterol) for ≥12 hours and 
other longer-acting agents (e.g. indacaterol, tiotropium) for ≥24 hours prior to the 
spirometry assessment 
In case the subject is on bronchodilators, he/she can use the bronchodilator at the end of the 
visit, after acceptability and repeatability as specified by or based on ATS/ERS/JRS/ALAT 
guidelines [19] has been confirmed by the central reader for the spirometry test. In case the 
subject has taken a bronchodilator before spirometry, the visit should be re-scheduled within 
the foreseen timeframe to allow spirometry assessment without bronchodilator. 
Spirometry parameters and calculation of predicted values 
The following parameters will be measured or calculated as part of the spirometry assessment: 
− 
FVC (mL) and %FVC  
− 
FEV1 (mL) and percent predicted forced expiratory volume in 1 second (%FEV1) 
− 
FEV1/FVC ratio 
− 
Forced expiratory flow between 25% and 75% of exhaled volume (FEF25-75) 
The ‘2012 Global Lung Function Initiative Equations’ will be used to calculate the predicted 
values [27]. 
If subjects, due to any COVID-19-related reason, cannot attend visits on site, see Section 
6.1.1. 
6.5.1.2. 
DLCO 
The DLCO test, corrected for Hb, will be performed according to local practice at the time 
points specified in the Schedule of Activities (Section 6.11). Each DLCO test should be 
performed using the same equipment. 
If subjects, due to any COVID-19-related reason, cannot attend visits on site, see Section 
6.1.1. 
 

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EQ VAS records the subject’s self-rated health on a vertical VAS and can be used as a 
quantitative measure of health outcome that reflects the subject’s own judgment. 
The SGRQ is a 50-item questionnaire split into three domains: symptoms (assessing the 
frequency and severity of respiratory symptoms), activity (assessing the effects of 
breathlessness on mobility and physical activity), and impact (assessing the psychosocial 
impact of the disease). Scores are weighted such that every domain score and the total score 
range from 0 to 100, with higher scores indicating a poorer health-related quality of life.  
The K-BILD health status questionnaire is a 15-item questionnaire split into three domains: 
psychological, breathlessness and activities, and chest symptoms. Scores are weighted such that 
every domain score and the total score range from 0 to 100, with higher scores indicating a 
better health status.  
Subjects with IPF commonly present with a (severe) non-productive cough. Cough will be 
evaluated using the LCQ. The LCQ is a 19-item questionnaire split into three domains: 
physical, psychological, and social. Scores are calculated by domain (range from 1 to 7) and 
then added to obtain the total score (range from 3 to 21, with higher scores indicating a better 
health status). 
VAS Cough and Urge to Cough will use a VAS of 100 mm with extremes “no cough” to “worst 
possible cough”, and “no urge” to “highest urge to cough”. 
These questionnaires will be completed electronically, using a tablet device at the clinical study 
center. Subjects must be able to read and complete the EQ-5D, SGRQ, K-BILD questionnaire, 
LCQ, and VAS Cough and Urge to Cough by themselves. They should not receive any help 
from anyone (such as family and friends or study staff) in interpreting or responding to the 
questions and need to complete the questionnaires in a quiet environment at the clinical study 
center.  
If subjects, due to any COVID-19-related reason, cannot attend visits on site, see Section 
6.1.1. 
6.5.4. Functional Exercise Capacity Testing: 6MWT 
A 6MWT will be performed at the clinical study center to assess pulmonary function at the time 
points specified in the Schedule of Activities (Section 6.11), and according to the manual 
provided.  
The 6MWT measures the distance that a subject can walk at his/her pace on measured, flat hard 
surface in a period of 6 minutes. The 6MWT has been established as the walk test of choice in 
cardiorespiratory diseases. The change in 6-Minute Walk Distance has been found to be highly 
predictive of mortality [6]. Also, the Minimal Clinical Important Difference (MCID) has been 
validated [21]. 
The 6MWT will be performed based on the ATS recommendations [1]
 
. The subject should not have a contraindication to perform the 
6MWT at any visit during screening and during the treatment period. Contraindications for 
performing the 6MWT are provided in Appendix 10. 

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At Visit 1, the 6MWT distance of 150 meters will have to be met to be eligible to proceed to 
Visit 2. The subject should not have a contraindication to perform the 6MWT (Appendix 10) 
or should not have a condition putting the subject at risk of falling during the test (investigator’s 
discretion). The use of a cane is allowed, the use of a stroller is not allowed at all for any 
condition. The test is performed under the usual conditions for the patient, with or without 
oxygen as applicable. 
At Visit 2, an oxygen titration test will be performed, according to the manual description. The 
subject should not have a contraindication to perform the 6MWT. For the oxygen titration test, 
resting SpO2 should be ≥88% with maximum 6 L O2/min. During the walk, SpO2 should be 
≥83% with maximum 6 L O2/minute or ≥88% with 0, 2 or 4 L O2/minute. A subject will not be 
eligible if these criteria are not met. 
For each following visit, the subject should not have a contraindication to perform the 6MWT. 
At Visit 3, 6MWT will be performed before IMP intake. For all visits after Visit 3 (Visits 9 and 
12, and every 24 weeks thereafter), 6MWT will be performed after IMP intake. The 6MWT 
will be done under the same oxygen requirements as the final result in the oxygen titration 
period (Visit 2). 
If subjects, due to any COVID-19-related reason, cannot attend visits on site, see Section 
6.1.1. 
6.5.5. 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
6.6. 
SAFETY ASSESSMENTS 
This section describes methods and timing for all safety assessments and recording. Additional 
assessments (e.g. unscheduled clinical laboratory tests or extra vital signs recordings) are 
allowed to ensure appropriate collection of safety data and to assess any perceived safety 
concerns.  
If subjects, due to any COVID-19-related reason, cannot attend visits on site, see Section 
6.1.1. 
6.6.1. Adverse Events 
The AE reporting period for safety surveillance begins when the subject signs the ICF and ends 
at his/her last follow-up visit.  
Detailed definitions, ratings, and reporting requirements for AEs and SAEs are found in 
Section 9. 

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6.6.2. Clinical Laboratory Evaluations 
Blood samples will be collected before IMP intake by venipuncture (or indwelling catheter) at 
the time points indicated in the Schedule of Activities provided in Section 6.11 (see also 
Section 6.1). In addition, urine samples for the clinical laboratory evaluations will be collected. 
Subjects do not need to be fasted at the time of sampling, unless specifically indicated. Clinical 
laboratory evaluations will be performed by the central laboratory. 
Blood and urine samples will be collected for the following clinical laboratory safety tests: 
- 
Hematology: hematocrit, mean corpuscular volume (MCV), mean corpuscular 
hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Hb, red blood 
cell count, white blood cell (WBC) count, WBC differential count (absolute and relative), 
and platelets. 
- 
Coagulation: activated partial thromboplastin time and prothrombin time, INR. 
- 
Clinical chemistry: random glucose, urea, creatinine, uric acid, sodium, potassium, 
calcium, chloride, phosphorus, AST, ALT, GGT, total bilirubin, alkaline phosphatase, 
lactate dehydrogenase, total serum bile acid, albumin, total proteins, triglycerides, 
cholesterol, high density lipoprotein, low density lipoprotein, amylase, lipase, and creatine 
kinase (CK) (CK- muscle/brain [CK-MB] to be performed if CK is elevated). 
- 
Urinalysis:  
• Dipstick: pH, glucose, proteins, blood, leucocytes; 
• Microscopic examination of the sediment (cylinders, erythrocytes, leucocytes), if 
indicated. 
- 
Serology: hepatitis B surface antigen and hepatitis C antibody, and HIV 1 and HIV 2 
antibodies only at screening. Positive hepatitis and HIV results should be reported by the 
investigator as required by local law. To assess eligibility, a positive hepatitis C antibody 
test should be confirmed by hepatitis C virus (HCV) RNA test. 
- 
FSH test for females at screening to confirm menopause, if applicable. 
- 
Urine pregnancy tests will be performed (only for WOCBP) on a monthly basis at home 
or at the clinical study center, with one additional test at the clinical study center at Visit 
4. At screening, a serum pregnancy test (beta-human chorionic gonadotropin) will be 
performed. A positive urine pregnancy test needs to be confirmed as soon as possible by a 
serum pregnancy test (local sample; central sample to be sent as well). 
Reference ranges will be supplied by the central laboratory. Clinical laboratory values outside 
the normal range will be flagged and clinical relevance will be assessed by the investigator. 
Clinically significant laboratory test abnormalities as judged by the investigator should be 
recorded as AEs. More frequent sampling as well as additional tests may be performed as 
deemed necessary by the investigator to follow up and resolve any safety concerns. In some 
circumstances, local laboratory results are allowed to be used (e.g. positive urine pregnancy 
test, abnormal liver function tests) for diagnosis of decision, but a central sample should also 
be collected and analyzed. 
The details of sample collection, handling, storage, and shipment instructions will be provided 
in a separate laboratory manual. 

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6.6.3. Physical Examination 
Physical examinations (including weight) will be conducted by a physician, trained physician’s 
assistant, or nurse practitioner (as acceptable according to local regulations) before IMP intake 
at visits specified in the Schedule of Activities in Section 6.11 (see also Section 6.1). At 
screening, height will be measured as well. The person conducting the physical examinations 
will document this in the subject’s medical records. Clinically significant abnormal findings 
should be recorded as AEs. 
6.6.4. Vital Signs 
Vital signs (heart rate, respiratory rate, SBP and DBP, and body temperature) will be recorded 
before IMP intake in a standardized manner (i.e. after the subject has rested in a supine position 
for 5 minutes) at visits specified in the Schedule of Activities in Section 6.11 (see also 
Section 6.1). Vital sign parameter normal ranges are presented in Appendix 8. Clinically 
significant abnormal values should be recorded as AEs. 
6.6.5. Electrocardiogram 
At the time points specified in the Schedule of Activities (see Section 6.11 and also Section 6.1), 
an ECG will be recorded. Triplicate ECGs will be performed at Visit 1 and at Visits 3 and 4 
(before and 2-3 hours after IMP intake). At all other time points, a single ECG will be performed 
before IMP intake (or irrespective of IMP intake at the ETD [if applicable] and EoST/EoSA 
visits). In addition, a single ECG will also be performed between 2 to 3 hours after IMP intake 
at Visits 5, 7, and 10. Central reading will be performed for all ECGs at all time points. The 
ECG must be taken after subjects rested for at least 5 minutes in the supine position. Triplicate 
ECGs will be taken within preferably 6 minutes, with an approximate 2-minute interval 
between ECGs. Each ECG will be interpreted by the investigator for clinical significance at the 
moment of the measurement. In case of abnormal findings, even if not clinically significant, a 
repeat ECG will be performed as soon as possible after the original abnormal recording within 
the same visit (if possible) and interpreted by the investigator. If the abnormal recording is 
discovered after the visit, the recording should be confirmed as soon as possible. 
For Visit 3, triplicate abnormal QTcF >450 msec (as described in exclusion criterion 8) predose 
readings (and confirmatory repeat as soon as possible after the abnormal recording within the 
same visit if possible) need to be transmitted immediately to the central reader for review before 
IMP intake by the subject. The result of the review will be transmitted to the investigator and 
preferably the CRO medical monitor (as per study contact list) or sponsor’s study physician (if 
the former is not available). The decision to dose the subject will be taken by the investigator, 
after consultation with the CRO medical monitor (as per study contact list) or sponsor’s study 
physician (if the former is not available). In case a timely response from the central reader is 
not available, the investigator will decide whether to dose the subject or not. If the QTcF at 
Visit 3 predose is reported during the visit as normal, but the overread by the cardiologist reports 
a QTcF >450 ms, then the recording should be confirmed as soon as possible and the 
investigator needs to justify the continuation of IMP documenting this in the source and 
continue to monitor the patient. 
At Visit 3 (after IMP intake) and Visit 4 (before and after IMP intake), abnormal triplicate 
ECGs and their confirmatory repeat reading will be transmitted to the central reader for 
expedited review. Refer to Section 4.5.4 for details on abnormal ECG readings. 

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For other time points with abnormal ECG reading, the investigator should alert the central 
reader. In that case, the ECG will be reviewed as soon as possible on the same day. The 
conclusion/evaluation of the central cardiologist reader will overrule the reading of the ECG 
device. 
At other time points with normal ECG reading, the standard review times will be adhered to. 
In case an indwelling catheter is used, ECGs may be recorded after blood sampling, provided 
that there is at least 30 minutes between catheter insertion and the ECG recording. When 
catheter insertion would fail, the ECG needs to be taken before the venipuncture and at least 
30 minutes after the failed attempt.  
ECG parameters to be recorded include the following: heart rate, PR interval, QRS interval, 
uncorrected QT interval, QTc, morphology, and rhythm. QTcF will be considered as normal if 
≤450 ms. A prolongation of QTcF to >500 ms or an increase from baseline of >60 ms will be 
considered a threshold of concern and the subject should be discontinued (for details, refer to 
Section 4.5.4). Normal ranges for ECG are provided in Appendix 8. 
ECG abnormalities will be interpreted by the investigator for clinical significance. Clinically 
significant abnormal values should be recorded as AEs. 
If subjects, due to any COVID-19-related reason, cannot attend visits on site, see Section 
6.1.1. 
6.7. 
PHARMACOKINETIC ASSESSMENTS 
PK assessments will include concentration analysis of GLPG1690, pirfenidone and 
nintedanib.  
Plasma concentrations of GLPG1690, pirfenidone or nintedanib will be measured using a 
validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method and 
will be performed by the bioanalytical laboratory in charge of these analyses (ARDENA 
Biochemical Laboratory).  
To be able to investigate the potential interactions between GLPG1690 and pirfenidone or 
nintedanib, the following samples will be collected to measure levels of GLPG1690 and 
pirfenidone or nintedanib (also see Table 1, and Schedule of Activities in Section 6.11). For 
subjects taking neither pirfenidone nor nintedanib, the samples need to be collected in relation 
to the specified IMP intake. 
− 
At Visit 1 (screening), for patients on nintedanib, the time of morning nintedanib intake 
will be verified by the investigator. Blood samples will be taken between 2-4 hours; and 
5-10 hours after the morning intake of nintedanib. 
− 
At Visits 3, 9, and 12, samples will be collected before IMP and pirfenidone or 
nintedanib morning intake. At these visits, the subject needs to take pirfenidone or 
nintedanib (as applicable) at the clinical study center. 
− 
For subjects taking nintedanib at screening and randomization, until they stop taking 
nintedanib:  
• 
At Visit 4, 5, 6, 7, 8, 10, and 11, samples will be collected 2-6 hours after the 
morning nintedanib intake and before IMP intake. At these visits, the subject needs 
to take nintedanib (as applicable) as per his or her regular routine, and record the 

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time of intake on the diary card. In addition, at Visits 7 and 10, samples will be 
collected 2-3 hours after IMP intake.  
• 
After Week 52 (Visit 12), samples will be collected 2-6 hours after the morning 
nintedanib intake and before IMP intake with a 12-week interval (until EoST/EoSA). 
At these visits, the subject needs to take nintedanib as per their regular routine, and 
record the time of intake on the diary card. 
− 
For subjects not taking nintedanib at screening and randomization and those stopping 
nintedanib during the study: 
• 
At Visits 7 and 10, samples will be collected after the pirfenidone or nintedanib 
morning intake and before IMP intake. At these visits, the subject needs to take 
pirfenidone or nintedanib (as applicable) as per his or her regular routine.  
In addition, samples will be collected 2 to 3 hours after IMP intake during these two 
visits. 
• 
After Week 52 (Visit 12), samples will be collected after the pirfenidone or 
nintedanib morning intake if applicable, but before IMP intake, with a 24-week 
interval (until EoST/EoSA). At these visits, the subject needs to take pirfenidone or 
nintedanib (as applicable) as per their regular routine.  
− 
At the ETD (if applicable) and EoST/EoSA visits, samples will be collected irrespective 
of IMP, pirfenidone, or nintedanib intake.  
The details on blood sample collection, handling, storage, and shipment instructions will be 
provided in a separate laboratory manual. 
If subjects, due to any COVID-19-related reason, cannot attend visits on site, see Section 
6.1.1. 

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performed in context of the described protocol (e.g. 
) and the data obtained 
may in no case be used for the purpose of identification or re-identification of subjects. 

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6.11. SCHEDULE OF ACTIVITIES 
For detailed instructions on the clinical study procedures, please see referred Sections and Section 6.1. 
6.11.1. Schedule of Activities: Screening and First 52 Weeks of Study Treatment 
For subjects who, for any COVID-19-related reason, cannot perform study procedures, extended visit windows, the possibility to conduct 
phone/televisits and home (or other remote location) visits, and alternative assessment procedures are detailed in Section 6.1.1. 
EVENT 
SCREENIN
G PERIOD 
FIRST 52 WEEKS OF STUDY TREATMENT 
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
ETD 
Study days (D) or weeks 
(W) 
± visit window  
D-28 to D-1 
D1 
W2 
(D15) 
±2 d 
W4 
(D29) 
±2 d 
W8 
(D57) 
±4 d 
W12 
(D85) 
±4 d 
W18 
(D127) 
±4 d 
W26 
(D183) 
±4 d 
W34 
(D237) 
±4 d 
W42 
(D295) 
±4 d 
W52 
(D365) 
±4 d 
 
Informed consent 
(Section 6.3) 
1 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (if applicable) and 
serology (Section 6.6.2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
HRCT sent for central 
review (Section 6.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
LB (if available) sent for 
central review (Section 6.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
(Sections 4.5.1, 4.5.2, 6.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics (Section 6.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
(Section 6.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 

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EVENT 
SCREENIN
G PERIOD 
FIRST 52 WEEKS OF STUDY TREATMENT 
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
ETD 
Study days (D) or weeks 
(W) 
± visit window  
D-28 to D-1 
D1 
W2 
(D15) 
±2 d 
W4 
(D29) 
±2 d 
W8 
(D57) 
±4 d 
W12 
(D85) 
±4 d 
W18 
(D127) 
±4 d 
W26 
(D183) 
±4 d 
W34 
(D237) 
±4 d 
W42 
(D295) 
±4 d 
W52 
(D365) 
±4 d 
 
Alcohol consumption and 
smoking habits 
(Section 6.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
(Section 6.6.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (Section 6.6.4) 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG triplicate recording 
(Section 6.6.5) 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG triplicate recording 
before IMP intake 
(Section 6.6.5) 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG triplicate recording 
2-3 hours after IMP intake 
(Section 6.6.5) 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG single recording 
before IMP intake 
(Section 6.6.5) 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG single recording 
2-3 hours after IMP intake 
(Section 6.6.5) 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG single recording 
(Section 6.6.5) 
 
 
 
 
 
 
 
 
 
 
 
 
 

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EVENT 
SCREENIN
G PERIOD 
FIRST 52 WEEKS OF STUDY TREATMENT 
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
ETD 
Study days (D) or weeks 
(W) 
± visit window  
D-28 to D-1 
D1 
W2 
(D15) 
±2 d 
W4 
(D29) 
±2 d 
W8 
(D57) 
±4 d 
W12 
(D85) 
±4 d 
W18 
(D127) 
±4 d 
W26 
(D183) 
±4 d 
W34 
(D237) 
±4 d 
W42 
(D295) 
±4 d 
W52 
(D365) 
±4 d 
 
Pregnancy test (serum) 
(Sections 6.6.2 
and 4.5.3.1.1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (urine) 
(Sections 6.6.2 
and 4.5.3.1.1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory tests 
(Section 6.6.2) 2  
 
 
 
 
 
 
 
 
 
 
 
 
 
Spirometry 
(Section 6.5.1.1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
DLCO (Section 6.5.1.2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Section 6.5.1.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
6MWT 
 
(Section 6.5.4) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization by IWRS 
(Section 4.6.1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense IMP (Section 5.2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collect IMP/perform drug 
accountability (Section 5.5) 
 
 
 
 
 
 
 
 
 
 
 
 
 

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EVENT 
SCREENIN
G PERIOD 
FIRST 52 WEEKS OF STUDY TREATMENT 
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
ETD 
Study days (D) or weeks 
(W) 
± visit window  
D-28 to D-1 
D1 
W2 
(D15) 
±2 d 
W4 
(D29) 
±2 d 
W8 
(D57) 
±4 d 
W12 
(D85) 
±4 d 
W18 
(D127) 
±4 d 
W26 
(D183) 
±4 d 
W34 
(D237) 
±4 d 
W42 
(D295) 
±4 d 
W52 
(D365) 
±4 d 
 
Diary card dispensing and 
collection (as applicable per 
visit) for drug 
accountability (Sections 5.5 
and 6.4) 
 
 
 
 
 
 
 
 
 
 
 
 
 
EQ-5D and SGRQ (ePRO) 
(Section 6.5.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
LCQ and K-BILD 
questionnaire (ePRO) 
(Section 6.5.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
VAS Cough and Urge to 
Cough (Section 6.5.3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intake P and N at clinical 
study center (Section 5.2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK blood samples 2-4 
hours after N morning 
intake (Section 6.7) 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK blood samples 5-10 
hours after N morning 
intake (Section 6.7) 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK blood samples before 
IMP and P or N intake 
(Section 6.7) 
 
 
 
 
 
 
 
 
 
 
 
 
 

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6.11.2. Schedule of Activities: After 52 Weeks of Study Treatment 
For subjects who, for any COVID-19-related reason, cannot perform study procedures, the possibility to conduct phone/televisits and home (or 
other remote location) visits, and alternative assessment procedures are detailed in Section 6.1.1. 
EVENT 
AFTER 52 WEEKS OF STUDY TREATMENT 
Study visit 
Every 12 weeks up to 
EoST/EoSA 
±7 d 
Every 24 weeks up 
to EoST/EoSA3 
±7 d 
ETD 
EoST/EoSA* 
FU* 
Study weeks  
± visit window  
 
 
(4 weeks after 
EoST/EoSA) 
±7 d 
Alcohol consumption and smoking habits (Section 6.3) 
 
 
 
 
 
Physical examination (Section 6.6.3) 
 
 
 
 
 
Vital signs (Section 6.6.4) 
 
 
 
 
 
ECG single recording (Section 6.6.5) 
 
 
 
 
 
ECG single recording before IMP intake (Section 6.6.5) 
 
 
 
 
 
Pregnancy test (urine) (Sections 6.6.2 and 4.5.3.1.1) 
 
 
 
 
 
Clinical laboratory tests (Section 6.6.2) 
 
 
 
 
 
Spirometry (Section 6.5.1.1) 
 
 
 
 
 
DLCO (Section 6.5.1.2) 
 
 
 
 
 
 (Section 6.5.1.3) 
 
 
 
 
 
6MWT 
 (Section 6.5.4) 
 
 
 
 
 
Dispense IMP (Section 5.2) 
 
 
 
 
 
Collect IMP/perform drug accountability (Section 5.5) 
 
 
 
 
 

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7. 
STATISTICAL METHODS 
All statistical methods shall be detailed in the statistical analysis plan (SAP) that will be 
finalized prior to the database lock and unblinding. Data collected in this clinical study will be 
documented using summary tables, figures, and subject data listings, as appropriate. 
All statistical analyses will be performed by the CRO using the SAS (Version 9.1.3 or higher) 
software for statistical computations and SAS or R Studio for graphical purposes.  
Any deviations from the statistical analyses planned in this protocol will be documented in the 
SAP. 
A protocol deviations plan will include the definition of major and minor protocol deviations 
and the identification of major protocol deviations which will be excluded from the per-protocol 
analysis. The assessments of protocol deviations (major/minor) will be done prior to database 
lock and unblinding. 
7.1. 
DETERMINATION OF SAMPLE SIZE 
To account for multiple testing due to multiple doses, a Bonferroni approach [9] will be applied 
to the alpha level with higher priority given to the high-dose group. The primary endpoint will 
be tested at a 4% level when comparing GLPG1690 600 mg to placebo and a 1% level for 
GLPG1690 200 mg group versus placebo.  
Denoting ∆600 and ∆200, the true treatment differences of the two GLPG1690 treatment groups 
with placebo, and assuming a common standard deviation (SD) on the 52 weeks decline in FVC 
of 275 mL, the probabilities that 0, 1, or 2 treatment comparisons with placebo are statistically 
significant, are presented in Table 2. The family-wise error rate is protected at 5% using the 
Bonferroni procedure. The so-called disjuncture power of the study is the probability that 1 or 
2 hypotheses are rejected and is displayed in the right-most column of Table 2.  
A meta-analysis of the seven placebo-controlled studies that have been conducted on 
nintedanib, pirfenidone, and pamrevlumab has revealed that the treatment effect at 52 weeks is 
estimated to be approximately 119 mL in a treatment-naïve population, the effect observed with 
nintedanib alone is similar (112 mL) [32]. Little information is available on the expected 
treatment effect of GLPG1690 in addition to pirfenidone or nintedanib.  Table 2 gives an 
overview of the power for different scenarios for the overall treatment effect in the population 
of subjects on standard of care (either pirfenidone or nintedanib, or neither pirfenidone nor 
nintedanib).  
Since the linear-slope model on the annual rate of decline in FVC accounts for missing data, 
the number of subjects randomized and the number of subjects included in the model is 
expected to be equal. An equal number of 250 subjects will be randomized to each treatment 
group to have at least 80% power to show a significant effect assuming the 600-mg group has 
a treatment effect of at least 80 mL in the overall population of treatment-naïve and patients on 
standard of care. 

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7.3. 
STATISTICAL ANALYSES 
7.3.1. General Statistical Considerations 
Summary tabulations will be presented and will display the number of observations, mean, SD 
or standard error, as appropriate, median, minimum, and maximum for continuous variables, 
and the number and percentage per category for categorical data. In addition to tabulated 
descriptive statistics, graphical data displays may be used to summarize the data. Unless 
otherwise noted, inferential statistics will be interpreted at the two-sided 5% level. 
7.3.2. Interim Analysis 
An IDMC will review the data of this study and the identically designed GLPG1690-CL-304 
study on a regular basis. An interim analysis to assess futility will be performed when a 
reasonable number of subjects have completed 52 weeks of treatment (e.g. at least 25% subjects 
from the two studies combined). No interim analysis for early termination for efficacy will be 
performed and therefore no adjustment of the alpha level is necessary. Details on the IDMC are 
given in Section 8.1 and in the charter. 
7.3.3. Analyses of Demographics and Baseline Characteristics 
Summary statistics (mean, median, SD, minimum, maximum, number of available 
observations) will be provided by treatment group for continuous demographic variables 
(e.g. age, height, weight). Categorical endpoints will be presented by number and percentage 
of subjects per category. Results will be presented for the full analysis set (FAS). 
Subject disposition (including reasons for early discontinuation), protocol deviations, 
demographics, baseline characteristics, medical history, prior and concomitant therapies, and 
use of IMP will be analyzed descriptively by treatment group and/or listed. No statistical 
inference will be performed.  
Medical history terms will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA) and presented by the number of subjects with at least one event by System Organ 
Class, Preferred Term, and treatment group.  
Prior and concomitant medications will be coded by the sponsor according to the World Health 
Organization (WHO) drug code and the Anatomical Therapeutic Classification (ATC) class 
code and tabulated by the number and percentages of subjects with a medication per ATC code 
and treatment group. 
7.3.4. Analyses of Efficacy Parameters 
Multiplicity Adjustment 
To account for the multiple testing due to two doses being compared to placebo, a Bonferroni 
approach [9] will be used with higher priority given to the high-dose group. The primary 
endpoint will be tested at a 4% level when comparing GLPG1690 600 mg to placebo and a 1% 
level for GLPG1690 200 mg group versus placebo.  

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Figure 4 
Multiplicity adjustment within study approach 
No interim analysis for early termination for efficacy will be performed and therefore, no 
adjustment of the alpha level is needed. 
Efficacy Analyses 
All efficacy parameters (e.g. spirometry, clinical endpoints, quality of life) will be analyzed 
descriptively and FVC and %FVC will also be analyzed for a series of subgroups (such as 
baseline characteristics, background treatment, and stratum). The primary analyses will be 
conducted on the FAS population. 
Spirometry Data 
− 
The primary time point will be Week 52. Analyses at the end of the study are secondary.  
− 
The rate of decline in FVC will be analyzed using a random coefficient regression model 
(linear slope model) including sex, age, height, and stratification factor as covariates and 
a random intercept and slope. The treatment effect is determined by using estimated 
average slopes for each treatment group on the basis of the treatment*time interaction 
term from the above mixed model, with time as a continuous factor and treatment as a 
categorical factor. All available FVC values from baseline to Week 52 will primarily be 
used, including those from the ETD visit for subjects who discontinued early and do not 
complete their study visits up to Week 52. 
− 
As a secondary analysis, the same model will be fit using all data until the end of the 
study. 
− 
The proportion of subjects who have an absolute decline ≥10% in %FVC at least once 
during the study or who die will be analyzed using logistic regression including sex, age, 
height, and stratum as factors using data up to Week 52. 
− 
In addition, the same will be presented using all data up to the end of the study. A 
time-to-event analysis may also be used to analyze the composite endpoint of %FVC 
decline and mortality up to the end of the study. 
− 
The %FVC change from baseline will be analyzed using a similar random coefficient 
regression model (linear slope model) as FVC in mL. 
− 
Other spirometry endpoints will be summarized descriptively, similar to FVC. 

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7.3.5.1. 
Extent of Exposure 
A subject’s extent of exposure to IMP will be generated from the IMP administration page of 
the CRF. Exposure data will be summarized by treatment group. Duration of exposure to IMP 
will be expressed as the number of weeks between the first and last dose of IMP, inclusive, 
regardless of temporary interruptions in IMP administration and summarized by treatment 
group. Results will be presented for the 52-week and for the complete study period, separately. 
7.3.5.2. 
Adverse Events 
Clinical and laboratory AEs will be coded using the latest version of the Medical Dictionary 
for Regulatory Activities. System Organ Class, High-Level Group Term, High-Level Term, 
Preferred Term, and Lower-Level Term will be attached to the clinical database. 
The following AEs will be considered as TEAEs:  
Any AE with an onset date on or after the start of IMP intake and no later than 30 days after 
last dose of IMP, or any worsening of any AE on or after the start of IMP intake.  
Selected tables will also be presented including all AEs which occurred after the start of IMP 
intake up to the end of the study. 
Summaries (number and percentage of subjects) of TEAEs by System Organ Class and 
Preferred Term will be provided by treatment group. TEAEs will also be summarized by causal 
relationship to IMP and severity. In addition, TEAEs leading to premature discontinuation of 
IMP will be summarized and listed. Also, all SAEs, including the non-treatment-emergent 
SAEs, will be listed. 
7.3.5.3. 
Clinical Laboratory Evaluations 
Laboratory assessments will be analyzed descriptively. Changes from baseline (Day 1 before 
IMP intake) and shifts according to normal ranges will be presented as well. Analyses will be 
done per treatment group.  
7.3.5.4. 
Physical Examinations 
Physical examination results will be summarized by body system and treatment group. 
7.3.5.5. 
Vital Signs 
Vital signs will be analyzed descriptively. Changes from baseline (Day 1 before IMP intake) 
and shifts according to normal ranges will be presented as well. Analyses will be done per 
treatment group.  
7.3.5.6. 
Electrocardiogram 
ECG will be analyzed descriptively. Changes from baseline (Day 1 before IMP intake) and 
shifts according to normal ranges will be presented as well. Frequency analyses of subjects with 
a QTc or QTcF prolongation of >500 ms and with a QTc or QTcF increase >60 ms change from 
baseline will be presented as well. Analyses will be done per treatment group. 

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who will then make a recommendation to the sponsor on the progress of the study. Specific 
details on timing of the analyses, futility criteria, and statistical analyses to be performed will 
be detailed in the IDMC charter or SAP, as appropriate. To allow collection of as much safety 
information as possible on a potential down-titration dose, a futile dose will continue if the other 
dose does not show futility. Either the study will continue as planned or both doses (and the 
study) will be terminated. Sponsor personnel will remain blinded and the study will not be 
stopped for a beneficial effect.  
8.2. 
CLINICAL ENDPOINT ADJUDICATION COMMITTEE 
The CEAC will consist of an independent group of experts that reviews and adjudicates clinical 
endpoints (see Section 6.5.2), as defined by the charter, in a blinded manner. This objective 
data adjudication will reduce variation in outcome reporting and observer bias. 
8.3. 
ADDITIONAL OPTIONAL INDEPENDENT REVIEW OF 
SAFETY DATA  
Selected safety data associated with liver function test (with or without symptoms) may be 
subjected to review in blinded manner by an independent expert panel as needed. 
9. 
SAFETY REPORTING 
9.1. 
DEFINITIONS OF ADVERSE EVENTS, SERIOUS ADVERSE 
EVENTS, AND SPECIAL SITUATIONS 
9.1.1. Adverse Events 
An AE is any untoward medical occurrence, new or worsening of any preexisting condition, in 
a clinical study subject administered a medicinal product and which does not necessarily has to 
have a causal relationship with this treatment.  
An AE can therefore be any unfavorable and unintended sign (for example, an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related. AEs may also include pre- or posttreatment 
complications that occur as a result of protocol-specified procedures, worsening of the targeted 
disease, overdose, drug abuse/misuse reports, or occupational exposure. Preexisting conditions 
that increase in severity or change in nature during or as a consequence of participation in the 
clinical study will also be considered AEs. 
9.1.2. Serious Adverse Events 
An SAE is defined as an AE that results in the following: 
- 
Death. 
- 
Life-threatening (Note: the term ‘life-threatening’ in the definition of ‘serious’ refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to 
an event that hypothetically might have caused death if it were more severe). 
- 
In-subject hospitalization or prolongation of existing hospitalization. 
- 
Persistent or significant disability/incapacity. 
- 
A congenital anomaly/birth defect. 

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- 
Medically significant (medical and scientific judgment should be exercised in deciding 
whether other situations should be considered serious such as important medical events 
that might not be immediately life-threatening or result in death or hospitalization but 
might jeopardize the subject or might require intervention to prevent one of the other 
outcomes listed in the definition above).  
9.1.3. Unlisted (Unexpected) Adverse Event/Reference Safety Information 
An AE is considered unlisted if the nature or intensity is not consistent with the applicable 
product reference safety information. For an IMP, the expectedness of an AE will be determined 
by whether or not it is listed in the reference safety information part of the IB (Edition 6, 28-
Jun-2019) and any relevant updates/addenda. 
9.1.4. Adverse Events of Special Interest 
Not applicable. 
9.1.5. Clinical Laboratory Abnormalities and Other Abnormal 
Assessments as Adverse Events or Serious Adverse Events 
Laboratory abnormalities without clinical significance based on the investigator’s judgment, 
are not considered AEs or SAEs. However, laboratory abnormalities (e.g. clinical chemistry, 
hematology, and urinalysis) or other abnormal (clinical study-specific) assessments (e.g. ECG, 
radiography, vital signs) that require medical or surgical intervention, are associated with signs 
and/or symptoms, or lead to IMP interruption, modification, or discontinuation must be 
recorded as an AE or SAE if they meet the definition as described in Sections 9.1.1 and 9.1.2, 
respectively. If the laboratory abnormality is part of a syndrome, the syndrome or diagnosis is 
to be reported (e.g. anemia instead of decreased Hb). 
The following liver enzyme elevations should be reported as SAEs: 
− 
AST or ALT ≥8xULN 
− 
AST or ALT ≥3xULN with signs of severe liver damage (i.e. with the appearance of 
fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or 
eosinophilia [>5%], and/or total bilirubin ≥1.5xULN or INR >1.5) 
9.1.6. Special Situations 
Special situations are situations that have a possible impact on the safe use of IMP. These 
situations might be or might not be associated with AEs. 
The investigator must report the following special situations within 24 hours of becoming 
aware, as indicated on Page 2 under “Emergency Contact Information”: 
− Pregnancy 
− Abuse or misuse of study drug 
• Abuse of study drug is defined as the persistent or sporadic, intentional excessive 
use of the study drug, which is accompanied by harmful physical or psychological 
effects. 
• Misuse of study drug is defined as a situation where the study drug is intentionally 
and inappropriately used not in accordance with the product information. 

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− Drug interaction or food interaction with study drug 
• A drug interaction with study drug is defined as a situation in which there is evidence 
or a suspicion that the study drug interacts with another drug when both are 
administered together. 
• 
A food interaction with study drug is defined as a situation in which there is evidence 
or a suspicion that the study drug interacts with a food when taken together. 
− Medication error with study drug 
• A medication error with study drug is defined as an unintended failure in the drug 
treatment process that leads to, or has the potential to lead to, harm to the patient. 
− Occupational exposure to study drug 
• Occupational exposure with study drug is defined as an exposure to the study drug 
as a result of one’s professional or non-professional occupation. 
− Overdose with study drug 
• An overdose of study drug is defined as the administration of a quantity of the study 
drug given per administration or cumulatively, which is the intake of more than 
three tablets/day. 
− Product complaint or quality defect of study drug 
• Product complaint or quality defect of study drug is defined as complaints or defects 
of the study drug arising from potential deviations in the manufacture, packaging, 
or distribution of the study drug. 
9.2. 
ASSESSMENT OF ADVERSE EVENTS AND SERIOUS 
ADVERSE EVENTS 
The investigator is responsible for assessing AEs and SAEs for causality and severity. This is 
the basis for the sponsor’s final review and confirmation of accuracy and completeness of event 
information and causality assessments. 
9.2.1. Assessment of Causality 
The investigator is responsible for assessing the causal relationship to IMP administration or 
study procedures (e.g. invasive procedures such as venipuncture) based on her/his clinical 
judgment. The following decision choice will be used by the investigator to describe the 
causality assessment between the reported event or laboratory test abnormality and the IMP. 
- 
Unrelated: 
− 
Relationship in time to IMP intake is improbable. Related to other etiologies such as 
concomitant medications or subject's clinical state.  
- 
Unlikely: 
− 
Relationship in time to IMP intake is improbable (but not impossible). Concomitant 
disease or other drugs provide plausible explanations. 
- 
Possible: 
− 
Relationship in time to IMP intake is reasonable. Event or laboratory test abnormality, 
could also be explained by disease or other drugs. Information on IMP withdrawal may 
be lacking or unclear. 

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- 
Probable: 
− 
Relationship in time to IMP intake is reasonable. Unlikely to be attributed to concurrent 
disease or other drugs. Response to withdrawal is clinically reasonable and rechallenge 
not required. 
- 
Certain: 
− 
Relationship in time to IMP intake is plausible. Cannot be explained by concomitant 
disease or other drugs. Response to withdrawal is plausible (pharmacologically, 
pathologically). Event definitive pharmacologically or phenomenologically (i.e. an 
objective and specific medical disorder or a recognized pharmacological phenomenon). 
Rechallenge satisfactory, if ethical and necessary. 
It should be emphasized that ineffective treatment (worsening of the disease) should not be 
considered as causally related in the context of AE reporting. 
9.2.2. Assessment of Severity 
The severity of AEs should be graded using the CTCAE version 5.0. If a CTCAE criterion does 
not exist, the investigator should use the grade or adjectives: Grade 1 (mild), Grade 2 
(moderate), Grade 3 (severe), Grade 4 (life-threatening) or Grade 5 (fatal) to describe the 
maximum intensity of the AE. For purposes of consistency with the CTCAE, these intensity 
grades are defined in Table 3. 
Table 3: 
Grading of AE Severity 
Grade  
Adjective  
Description  
Grade 1  
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated  
Grade 2  
Moderate 
Local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL*  
Grade 3  
Severe 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL**  
Grade 4  
Life-threatening 
Urgent intervention indicated  
Grade 5  
Death 
Death-related AE  
* Activities of Daily Living (ADL) Instrumental ADL refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc. 
** Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
For AEs associated with laboratory abnormalities, the event should be graded on the basis of 
the clinical severity in the context of the underlying conditions; this may or may not be in 
agreement with the grading of the laboratory abnormality. This is upon the investigator’s 
assessment. 
If there is a change in intensity (worsening or improvement) of an AE, it must be recorded. 
9.2.3. Outcome 
Each AE must be rated by choosing among: 
− Recovered/resolved; 
− Recovered/resolved with sequelae; 
− Recovering/resolving; 
− Not recovered/not resolved; 

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− Fatal; 
− Unknown. 
9.3. 
INVESTIGATOR REQUIREMENTS AND INSTRUCTIONS FOR 
REPORTING ADVERSE EVENTS / SERIOUS ADVERSE 
EVENTS /PREGNANCIES AND OTHER SPECIAL SITUATIONS 
TO THE SPONSOR 
9.3.1. Adverse Events 
The AE reporting period for safety surveillance begins when the subject signs the ICF and ends 
at the subject’s last follow-up visit (the last follow-up visit after the last dose of IMP). In this 
period, all new AEs, regardless of cause or relationship, derived by spontaneous, unsolicited 
reports of subjects, by observation, and by routine open questioning (such as “How do you 
feel?”) need to be recorded in the source and in the CRF.  
In case an AE is ongoing at the time of the last follow-up visit, the investigator needs to follow 
the subject until AE resolution or reasonable stabilization and to document in the subject’s 
source documentation. No related updates or additional data on the AE should be reported in 
the CRF.  
If a subject is documented as lost-to-follow-up, ongoing or unknown outcome AEs will not be 
followed up. 
If the AE meets the criteria for seriousness, the SAE form must be completed and sent to the 
sponsor within 24 hours (see Section 9.3.2). 
9.3.2. Serious Adverse Events 
Subjects experiencing an SAE or an emergency situation will be examined by a physician as 
soon as possible. The subject will remain under observation as long as medically indicated. 
Appropriate laboratory tests will be performed until all parameters return to normal or are 
otherwise explained or stable.  
All SAEs, whether or not deemed IMP-related, must be recorded in the CRF and on the 
SAE form. The investigator must report each SAE immediately, and under no circumstances 
should this exceed 24 hours following the knowledge of the SAE, as is indicated on page 2 
under “Emergency Contact Information”. 
The SAE form should at least contain identifiers of the subject and the reporter, SAE term, and 
statement of relatedness to the IMP, and at a later stage if not yet available within 24 hours, the 
form needs to be completed with a clearly written narrative describing signs, symptoms, and 
treatment of the event, diagnostic procedures, as well as any relevant laboratory data and any 
sequelae. 
Follow-up and outcomes should be reported and documented in the source documents for all 
subjects that experience an SAE. It is important that the information provided on the SAE form 
matches the information recorded on the CRF for the same event. 
Copies of additional laboratory tests, consultation reports, post-mortem reports, hospital case 
reports, autopsy reports, and other documents should be sent when requested and available. 

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Only subject identifiers (subject number) should appear on the copies, and all names and initials 
should be blackened and rendered illegible. Follow-up reports relative to the subject’s 
subsequent course must be submitted until the event has subsided or, in case of permanent 
impairment, until the condition stabilizes. 
Any SAEs that occur after the posttreatment follow-up visit but within 30 days of the last dose 
of IMP, regardless of causality, should also be reported (Emergency Contact Information on 
page 2). Investigators are not obligated to actively seek SAEs after the protocol-defined 
follow-up period. However, if the investigator is informed about an SAE that occurs at any time 
after the subject’s posttreatment follow-up visit and the event is deemed relevant to the use of 
IMP(s), he/she should promptly document and report the event to the sponsor by using the SAE 
form. 
9.3.3. Pregnancy 
All initial reports of pregnancy in female subjects and pregnancies in partners of male subjects 
included in the clinical study must be recorded and documented in the source documents and 
on the pregnancy form. The investigator must report each pregnancy immediately, and under 
no circumstances should this exceed 24 hours following the knowledge of the pregnancy, as is 
indicated on Page 2 under “Emergency Contact Information”. 
All pregnancies should be followed up until delivery or pregnancy interruption. The 
investigator will contact the subject/partner of the subject at the expected time of delivery for 
follow-up and for information regarding the outcome of the newborn. Abnormal pregnancy 
and/or abnormal newborn outcomes are considered SAEs and must be reported using the SAE 
form. 
9.3.4. Reporting of Special Situations (Other Than Pregnancy) and 
Associated Adverse Events 
In case a special situation is not associated with an AE, the special situation should be reported 
within 24 hours by using the Special Situations form. 
In case a special situation is associated with an AE, the special situation should be reported 
within 24 hours by using the Special Situations form and the associated AE should be reported 
as specified in Section 9.3.1. 
In case a special situation is associated with an SAE, the special situation should be reported 
within 24 hours by using the SAE form (and not the Special Situations form) and the associated 
SAE should be reported as specified in Section 9.3.2. 
9.4. 
SPONSOR REPORTING REQUIREMENTS 
Depending on relevant local legislation or regulations, including the applicable United States 
Federal Drug Administration Code of Federal Regulations, the European Union Clinical Trials 
Directive (2001/20/EC) and relevant updates, and other country-specific legislation or 
regulations, the sponsor may be required to expedite to worldwide regulatory agencies reports 
of SAEs, serious adverse drug reactions, or suspected unexpected serious adverse reactions 
(SUSARs). The sponsor or a specified designee will notify worldwide regulatory agencies and 
the relevant IEC/IRB in concerned Member States of applicable SUSARs as outlined in current 
regulations. 

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Assessment of expectedness for SAEs will be determined using reference safety information 
section in the IB (Edition 6, 28-Jun-2019) and any relevant updates/addenda or relevant local 
label, as applicable.  
All concerned investigators will receive a safety letter notifying them of relevant 
SUSAR reports associated with any IMP. The investigator should notify the IEC/IRB of 
SUSAR reports as soon as is practical, where this is required by local regulatory agencies, and 
in accordance with the local institutional policy. 
10. 
SPONSOR’S AND INVESTIGATOR’S RESPONSIBILITIES 
This clinical study is conducted in accordance with the current applicable regulations, 
ICH-GCP Guideline E6, EU Directive 2001/20/EC and its updates, and local ethical and legal 
requirements. 
GCP is an international ethical and scientific quality standard for designing, conducting, 
recording, and reporting studies that involve the participation of human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of clinical 
study subjects are protected, consistent with the principles that have their origin in the 
Declaration of Helsinki (1996 and successive amendments), and that the clinical study data are 
credible. 
The name and address of each third-party vendor (e.g. CRO) used in this study and the sponsor’s 
study team members will be maintained in the investigator’s and sponsor’s files as appropriate. 
10.1. SPONSOR’S RESPONSIBILITIES 
10.1.1. Regulatory Approval / Notification 
Prior to clinical study start, this protocol together with all relevant documentation will be 
submitted to the local Regulatory Authorities for review and approval and/or notification in 
compliance with local requirements.  
10.1.2. Clinical Study Closure Considerations 
The sponsor reserves the right to close the clinical study center or end the clinical study at any 
time for any reason. In case of an early termination of the clinical study or temporary halt by 
the sponsor, the IEC/IRB should be notified within 15 calendar days unless otherwise specified 
by the IEC/IRB, including a detailed written explanation of the reasons for the termination/halt. 
The end of clinical study declaration will be submitted to the regulatory authorities and IEC/IRB 
after the complete clinical study has ended in all participating clinical study centers, in all 
countries. This notification will also be submitted within 90 days of the end of the clinical study 
in a given country/member state or within the timelines required by the local regulations. 
Reasons for the closure of a clinical study center include, but are not limited to: 
- 
Successful completion of the clinical study at the clinical study center. 
- 
The overall required number of subjects for the clinical study has been recruited.  
- 
Failure of the investigator to comply with the protocol, ICH-GCP guidelines or local 
requirements. 

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- 
Inadequate recruitment of subjects by the investigator. 
Reasons for early termination of a clinical study by the sponsor may include but are not limited 
to: 
- 
Safety concerns. 
- 
Sufficient data suggesting lack of efficacy. 
10.1.3. Indemnification 
Under the conditions of a contract concluded between investigator, clinical study center, and 
sponsor or designee, which shall prevail, sponsor shall, except in case of gross negligence or 
willful misconduct, indemnify and hold harmless the investigator and his/her medical staff from 
any claim arising from the clinical study activities carried out in compliance with the protocol, 
sponsor’s instructions and applicable local regulations. 
The investigator must notify the sponsor immediately upon notice of any claims or lawsuits. 
10.1.4. Insurance 
Sponsor shall maintain insurance coverage that is sufficient to cover its obligations and that is 
consistent with human clinical study local regulations. Save in case of gross negligence or 
willful misconduct of the investigator, and provided that the subject has been treated according 
to the protocol and sponsor’s instructions, any injury caused to a subject which is the direct 
result of his/her participation to the clinical study shall be covered by sponsor’s insurance. 
10.1.5. Reporting 
Where required by IEC/IRB per local requirements, at least once a year the investigator will 
provide the IEC/IRB with a progress report to allow review of the clinical study (see 
Section 10.4.1). At the end of the clinical study, the results of the clinical study will be reported 
in a single clinical study report. A summary or full report, depending on the requirements, will 
be provided to the investigators, to the applicable regulatory authorities and IECs/IRBs if 
required by the applicable regulatory requirements within 1 year, or 6 months for pediatric 
studies, after the end of the clinical study. 
10.1.6. Publication 
It is understood by the investigator that the sponsor shall be free to use the compound-related 
information which is generated during the clinical study and may disclose it to other clinical 
investigators and to regulatory agencies. As a consequence, the investigator agrees to provide 
all clinical study results and data generated during this clinical study to the sponsor. 
The investigator shall not be authorized to submit the results of this clinical study and any data 
for publication or presentation without the prior written approval of the sponsor which shall not 
be unreasonably withheld.  
However, it is understood and agreed by the investigators that their results and/or findings shall 
not be authorized for publication prior to sponsor’s publication of the overall clinical study 
results. The investigator agrees that prior to the publication of any results, he/she shall provide 
sponsor with a draft copy of the intended publication. Sponsor shall have the right to review it 
and to make any comments. In accordance with generally accepted scientific collaboration 

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principles, co-authorship with any staff member sponsor involved in the clinical study, will be 
discussed and mutually agreed upon before submission of any manuscript to a publisher. 
10.2. INVESTIGATOR’S RESPONSIBILITIES 
10.2.1. Financial Disclosure 
The disclosed financial interest of the investigators must be collected before screening of the 
first subject, following clinical study completion at the clinical study center, and 1 year 
following overall clinical study completion. The investigators should promptly update this 
information if any relevant changes occur during this period. Disclosable financial interests will 
be recorded on the Investigator Financial Disclosure Form. 
Any investigator(s) added as investigational staff must complete the Investigator Financial 
Disclosure Form at the beginning of their participation in the clinical study. For any 
investigator(s) leaving the clinical study center prior to clinical study completion, an 
Investigator Financial Disclosure Form should be obtained at the end of their contribution to 
the clinical study. 
10.2.2. Source Data and Data Capture 
The nature and location of all source documents need to be identified and documented to ensure 
that all sources of original data required to complete the CRF are known and are accessible for 
verification by the monitor.  
Source data may be directly captured from devices transferred from third partners 
(e.g. laboratory data) or entered manually into the CRF. The CRF completion guidelines will 
be provided to each investigational site. 
It is recommended that the author of an entry in the source documents should be identifiable. 
Following ICH-GCP Guidelines, direct access to source documents must be granted for the 
purpose of verifying that the data recorded in the CRF are consistent with the original source 
data. 
10.2.3. Archiving 
The investigator shall maintain the clinical study specific documents as specified in Section 8 
“Essential Documents for the Conduct of a Clinical Study” of the ICH-GCP Guidelines and as 
required by the applicable regulatory requirement(s). The investigator should take measures to 
prevent accidental or premature destruction of these documents. 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IMP. These documents should be retained for a 
longer period however if required by the applicable regulatory requirements or by an agreement 
with the sponsor. 
Under no circumstance shall the investigator relocate or dispose of any clinical study documents 
before having obtained a written approval of the sponsor. 

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If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this clinical study, the investigator must permit access to such reports. 
The subject is granting access to his/her source data by signing the ICF. 
Any difficulty in storing original documents must be discussed with the monitor prior to the 
initiation of the clinical study.  
10.2.4. Participation Cards 
If the subjects are not under 24-hour supervision of the investigator or his/her staff 
(out-subjects), they must be provided with a subject participation card indicating the name of 
the IMP, the clinical study number, the investigator's name and a 24-hour emergency contact 
number. The subject should be advised to keep the participation card in his/her wallet at all 
times. 
10.3. CONFIDENTIALITY 
All information concerning the product and the sponsor’s operations (such as patent 
applications, formulae, manufacturing processes, basic scientific data, or formulation 
information supplied to the investigator by the sponsor and not previously published) is 
considered confidential by the sponsor and should not be disclosed by the investigator to any 
third party without the sponsor’s prior written approval. The investigator agrees to use this 
information only in accomplishing the clinical study and will not use it for other purposes. 
In order to permit easy identification of the individual subject during and after the clinical study, 
the investigator is responsible for keeping an updated Subject Identification Code List. The 
monitor will review this document for completeness. However, the investigator must guarantee 
the subject’s anonymity will be maintained. Therefore, in order to ensure subject 
confidentiality, the Subject Identification Code List will remain at the clinical study center and 
no copy will be made. 
The subject will receive all information as required by the EU General Data Protection 
Regulation, including the identity of the controller, the clinical research purposes, the fair 
processing of his/her data, and all his/her data subject rights. All details are listed in the ICF. 
10.4. ETHICAL CONSIDERATIONS 
10.4.1. Independent Ethics Committee / Institutional Review Board 
This clinical study can only be undertaken after full approval of the protocol, ICF, any other 
written information given to subjects, and subject recruitment materials has been obtained from 
the IEC/IRB. This approval document must be dated and clearly identify the clinical study and 
the related clinical study documents being approved, including the subject compensation 
programs, if applicable. 
During the course of the clinical study, at least the following documents will be provided to the 
IEC/IRB per local requirements: 
- 
Changes to the IB 
- 
Reports of AEs that are serious, unlisted, and associated with the investigational drug (in 
compliance with IEC/IRB, per local requirements) 

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- 
Protocol amendments 
- 
Informed consent revision(s) 
Protocol amendments and applicable ICF revisions must promptly be submitted to the IEC/IRB 
for review and approval prior to implementation of the change(s), except when necessary to 
eliminate an immediate hazard to the clinical study subjects, or according to local requirements. 
The IEC/IRB is responsible for continuous review of the clinical study. Where required by 
IEC/IRB per local requirements, at least once a year the investigator will provide the IEC/IRB 
with a progress report to allow review of the clinical study. Additional progress reports should 
be provided according to local legal requirements. These requests and (re) approvals, if 
applicable, should be documented in writing. 
10.4.2. Informed Consent 
The investigator or designated personnel must explain the clinical study and the implications 
of participation (e.g. objectives, methods, anticipated benefits, and possible risks) to potential 
subjects according to applicable regulations prior to any clinical study-related activity. Subjects 
will be informed that their participation is voluntary and that they may withdraw from the 
clinical study at any time. They will be informed that choosing not to participate or to withdraw 
from the clinical study will not have an impact on the care the subject will receive for the 
treatment of his/her disease. In case the subject is unable to read and/or write, oral consent in 
the presence of at least one impartial witness who was also included when the affected person 
was being informed may be given. The witness may not be anyone working at the trial site nor 
a member of the investigating team. The orally given consent shall be documented in writing, 
dated and signed by the witness.  
The subject will be given sufficient time to read the ICF and to ask additional questions. After 
this explanation and before entry in the clinical study, consent should be appropriately recorded 
by means of the subject's personally dated signature (or, if applicable, by the signature of an 
independent witness who certifies the subject's consent in writing) and by the investigator’s 
signature. After having obtained the consent, a copy of the signed and dated ICF must be given 
to the subject. 
If new information becomes available that may be relevant to the subject’s willingness to 
participate in the clinical study, the subject will be informed in a timely manner by means of an 
updated ICF. This amended ICF will be signed and dated by the subject (or, if applicable, by 
an independent witness) and the investigator to document the willingness of the subject to 
continue with the clinical study. 
This signed and dated amended version will be filed together with the initial signed and dated 
ICF. 
Additional consent needs to be obtained from the subjects to allow collection of the 
 
 evaluation if approved by the local IEC/IRB (see also Section 6.9.2).  
A pregnant partner, who agrees that information will be gathered about her pregnancy, will sign 
a specific ICF to participate in the data collection.  
Data about the health of the baby will be collected if the parents agree with the data collection 
and sign the specific ICF. 

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10.5. DATA QUALITY CONTROL / ASSURANCE 
10.5.1. Monitoring 
This clinical study will be monitored by sponsor representatives according to their current 
Standard Operating Procedures for the monitoring of clinical studies as described in the 
monitoring plan. 
To guarantee adequate protection of the subjects and to guarantee the quality of the data, the 
sponsor will ensure oversight of any clinical study-related duties and functions carried out on 
its behalf, including clinical study-related duties and functions that are subcontracted to another 
party by the sponsor’s contracted CRO(s). 
To ensure subjects’ safety, protocol compliance, and the quality of the data at all times, remote 
data monitoring may be utilized for this study. If allowed by local regulations, study monitors 
may perform remote source data verification, as per monitoring plan, to confirm that source 
data entered into the eCRFs by authorized site personnel are accurate and complete. 
10.5.2. Audit and Inspection 
To ensure compliance with relevant regulations, an independent quality assurance 
representative, regulatory authorities and/or IECs/IRBs may review this clinical study. This 
implies that auditors/inspectors will have the right to inspect the clinical study center(s) at any 
time during and/or after completion of the clinical study and will have access to the data 
generated during the clinical study, source documents, and subject's files. By participating in 
this clinical study, investigators agree to this requirement.  
 

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13. King T., Bradford W., Castro-Bernardini S., et al., "A phase 3 trial of pirfenidone in 
patients with idiopathic pulmonary fibrosis," N Eng J Med, vol. 370, pp. 2083-2092, 
2014.  
14. Ley B., Collard H. and King T. J., "Clinical course and prediction of survival in 
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15. Lynch D., Sverzellati N., Travis W., et al., "Diagnostic criteria for idiopathic pulmonary 
fibrosis: a Fleischner Society White Paper," Lancet Respir Med, vol. 6(2), pp.138-153, 
2017. 
16. Macintyre N., Crapo R., Johnson D., et al., "Standardisation of the single-breath 
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17. Magkrioti C. and Aidinis V., "Autotaxin and lysophosphatidic acid signalling in lung 
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19. Miller M., Hankinson J., Brusasco V., et al., "Standardisation of spirometry," Eur Respir 
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20. Montesi S., Mathai S., Brenner L., et al., "Docosatetraenoyl LPA is elevated in exhaled 
breath condensate in IPF," BMD Pulm Med, vol. 14(5), pp.1-7, 2014.  
21. Nathan S.D., du Bois R.M., Albera C., et al., "Validation of test performance 
characteristics and minimal clinically important difference of the 6-minute walk test in 
patients with idiopathic pulmonary fibrosis," Respir Med, vol. 109(7), pp. 914-922, 2015. 
22. Navaratnam V., Fleming K., West J., et al., "The rising incidence of idiopathic 
pulmonary fibrosis in the UK," Thorax, vol. 66(6), pp. 462-467, 2011.  
23. Noble P., Albera C., Bradford W., et al., "Pirfenidone in patients with idiopathic 
pulmonary fibrosis," Lancet, vol. 377, pp. 1760-1769, 2011.  
24. Ofev. Summary of Product Characteristics.  
25. Oikonomou N., Mouratis M., Tzouvelekis A., et al., "Pulmonary autotaxin expression 
contributes to the pathogenesis of pulmonary fibrosis," Am J Respir Cell Mol Biol, 
vol. 47(5), pp. 566-574, 2012.  
26. Paterniti M.O., Bi Y., Rekic D., et al., "Acute exacerbation and decline in forced vital 
capacity are associated with increased mortality in idiopathic pulmonary fibrosis," Ann 
Am Thorac Soc., vol. 14(9), pp. 1395-1402, 2017. 
27. Quanjer P., Stanojevic S., Cole T., et al., "Multi-ethnic reference values for spirometry 
for the 3-95 year age range: the global lung function 2012 equations: Report of the Global 
Lung Function Initiative (GLI), ERS Task Force to establish improved Lung Function 
Reference Values.," Eur Respir J, vol. 40(6), pp. 1324-1343, 2012.  
28. Raghu G., Collard H., Egan J., et al., "An official ATS/ERS/JRS/ALAT statement: 
idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and 
management," Am J Respir Crit Care Med vol. 183, pp. 788-824, 2011.  
29. Raghu G, Remy-Jardin M, Myers JL, et al. American Thoracic Society, European 
Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. 
“Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical 
Practice Guideline.” Am J Respir Crit Care Med. Vol. 198(5), e44-e68, 2018. 
30. Raghu G., Rochwerg B., Zhang Y., et al., "An official ATS/ERS/JRS/ALAT clinical 
practice guideline: treatment of idiopathic pulmonary fibrosis," Am J Respir Crit Care 
Med, vol. 192, pp. e3-e19, 2015.  
31. Raghu G., Weycker D., Edelsberg J., et al., "Incidence and prevalence of idiopathic 
pulmonary fibrosis," Am J Respir Crit Care Med, vol. 174, pp. 810-816, 2006.  
32. Richeldi L., Cottin V., du Bois RM., et al., "Nintedanib in patients with idiopathic 
pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS® trials," 
Resp Med, vol 113, pp. 74-79, 2016. 
33. Richeldi L., du Bois R., Raghu G., et al., "Efficacy and safety of nintedanib in idiopathic 
pulmonary fibrosis," N Engl J Med, vol. 370, pp. 2071-2082, 2014.  
34. Spagnolo P., Del Giovane C., Luppi F., et al., "Non-steroid agents for idiopathic 
pulmonary fibrosis (review)," Cochrance Database Syst Rev, (9):CD003134, 2010.  
35. Tager A., LaCamera P., Shea B., et al., "The lysophophatidic acid receptor LPA1 links 
pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak," 
Nat Med, vol. 14(1), pp. 45-54, 2008.  
36. Tanaka M., Okudaira S., Kishi Y., et al., "Autotaxin stabilizes blood vessels and is 
required for embryonic vasculature by producing lysophosphatidic acid," J Biol Chem, 
vol. 281(35), pp. 25822-25830, 2006.  
37. Taniguchi H., Ebina M., Kondoh Y., et al., "Pirfenidone in idiopathic pulmonary 
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38. Thomeer M., Costabe U., Rizzato G., et al., "Comparison of registries of interstitial lung 
diseases in three European countries," Eur Respir J Suppl, vol. 32, pp. 114s-118s, 2001.  
39. Tsuda S., Okudaira S., Moriya-Ito K., et al., "Cyclic phosphatidic acid is produced by 
autotaxin in blood," J Biol Chem, vol. 281(36), pp. 26081-26088, 2006. 
40. Xu M., Porte J., Knox A., et al., "Lysophosphatidic acid induces αvβ6 integrin-mediated 
TGF-β activation via the LPA2 receptor and the small G protein Gαq," Am J Pathol, vol. 
174(4), pp. 1264-1279, 2009.  
41. Wuyts W., Antoniou K., Borensztajn K., et al., "Combination therapy: the future of 
management for idiopathic pulmonary fibrosis?," Lancet Respiratory Medicine, vol. 2, 
pp. 933-942, 2014. 
 
 

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APPENDICES 
APPENDIX 1: 
HRCT/BIOPSY CENTRAL REVIEW CRITERIA 
All chest HRCTs and histopathology slides of LBs (if available) will be centrally reviewed by 
two radiologists with adjudication by a third radiologist if indicated and one histopathologist to 
confirm the diagnosis of IPF (if required) and therefore eligibility of the subject for the study. 
The diagnostic criteria for idiopathic pulmonary fibrosis, published as the Fleischner Society 
White Paper [15], will be used to determine eligibility of the subject for the trial. 
In case a historical LB is available, this will be used as complementary information and will 
allow confirmation of UIP-IPF in certain cases. An algorithm to be used by the radiologists and 
the histopathologist to determine eligibility is available in the relevant manual. 
After central review of the HRCT, subjects will be considered eligible if:  
− 
The majority of the central readers evaluate the HRCT as showing a typical and/or 
probable IPF pattern, unless a historical LB, if available, is not in accordance with this 
diagnosis (i.e. is most consistent with an alternative diagnosis) 
− 
The majority of the central readers evaluate the HRCT as showing a pattern indetermined 
for IPF and/or a pattern most consistent with non-IPF diagnosis, but an available 
historical LB, shows a definite UIP-IPF pattern. 
The LB will not be evaluated if both 2 initial central reviewers evaluate the HRCT as showing 
the following pattern: 
− 
Typical UIP-IPF pattern + Typical UIP-IPF pattern 
− 
IPF pattern most consistent with Non-IPF diagnosis + IPF pattern most consistent with 
Non-IPF diagnosis 
 
 

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APPENDIX 2: 
DLCO 
At Visit 1 (screening visit 1), DLCO must meet the following criteria [16]:  
− 
DLCO corrected for Hb ≥30% predicted of normal 
For predicted normal values, different clinical study centers may use different prediction 
formulas, based on the method used to measure DLCO. In any case, the method used must be 
in compliance with the ATS/ERS task force guideline on DLCO measurements [16] and the 
prediction formula appropriate for that method.  
Raw data (gas mixture, equation used for prediction of normal) must be captured.  
DLCO corrected for Hb:  
− 
Males: DLCO corrected for Hb = DLCO measured x (10.22+Hb) /1.7Hb  
− 
Females: DLCO corrected for Hb = DLCO measured x (9.38+Hb)/1.7Hb  
Hb is expressed in g/dL.  

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APPENDIX 3: 
KNOWN CYP2C8 SUBSTRATES 
Excluded and prohibited medication: 
Amiodarone 
Buprenorphine 
Amodiaquine; Chloroquine 
Repaglinide 
Rosiglitazone, pioglitazone 
Verapamil 
Zopiclone 
This list is intended as a guidance for the investigator. 

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APPENDIX 4: 
KNOWN STRONG CYP3A4 INDUCERS AND POTENT 
P-GP INDUCERS 
Excluded and prohibited medication: 
Barbiturates  
Carbamazepine 
Glucocorticoids: prednisone or equivalent > 10 mg/day 
Modafinil 
Oxcarbazepine 
Phenytoin 
Pioglitazone 
Rifabutin 
Rifamp(ic)in 
St. John’s Wort 
This list is intended as a guidance for the investigator. 

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APPENDIX 5: 
KNOWN STRONG CYP3A4 INHIBITORS 
Excluded and prohibited medication: 
Clarithromycin 
Itraconazole 
Ketoconazole 
Nefazodone 
Telithromycin 
Voriconazole 
This list is intended as a guidance for the investigator. 

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APPENDIX 6: 
KNOWN POTENT P-GP INHIBITORS  
Excluded and prohibited medication: 
Amiodarone 
 
Azithromycin – Clarithromycin – Erythromycin – Roxithromycin – Telithromycin 
(unless used under the condition described in Section 4.5.3.2) 
Cyclosporine 
Itraconazole - Ketoconazole 
Tamoxifen 
Verapamil 
This list is intended as a guidance for the investigator. 

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APPENDIX 7: 
MEDICATION KNOWN TO PROLONG QT 
INTERVAL  
Medication to be used with caution: 
Disopyramide 
Dofetilide 
Flecainide 
Ibutilide 
Quinidine 
Sotalol 
This list is intended as a guidance for the investigator. 

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APPENDIX 8: 
NORMAL RANGES FOR VITAL SIGNS, 
 
 AND ECG PARAMETERS 
NORMAL RANGES FOR VITAL SIGNS 
Normal ranges applicable in supine position (after at least 5 minutes): 
SBP (mmHg) 
DBP (mmHg) 
Heart 
rate 
(bpm) 
Body 
temperature 
(°C) 
Respiratory rate 
(RR) 
(breaths/minute) 
90≤ SBP ≤150 
45≤ DBP ≤90 
50≤ HR 
≤100 
35.5≤ t ≤37.5 
12≤ RR ≤18 
bpm = beats per minute 
 
 
NORMAL RANGES FOR ECG PARAMETERS 
Normal ranges applicable in supine position (after 5 minutes): 
PR (ms) 
QRS (ms) 
QTcF (ms) 
Heart rate (bpm) 
120 PR 220 
QRS 120 
QTcF ≤450  
50≤ HR ≤100 

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APPENDIX 9: 
ALGORITHM FOR ELEVATED LIVER FUNCTION 
TESTS 
 
 
AST or ALT increase to 
 
≥1.5x to 
3xULN 
≥3x to 5xULN 
≥5x to 8xULN 
≥3xULN with signs 
of severe liver 
damage1 
≥8xULN 
Visit 1 
(screening) 
Not eligible 
Not eligible 
Not eligible 
Not eligible 
Not eligible 
Visit 3 
(randomization) 
Discontinue 
IMP2 
Discontinue 
IMP2 
Discontinue 
IMP2 
Discontinue IMP2 
Discontinue 
IMP2 
From Visit 4 
onwards 
Continue as 
planned 
Down-
titration: 
reduce or 
interrupt IMP 
for at least 
2 weeks 
Close 
observation2  
Down-
titration: 
interrupt IMP 
for at least 
2 weeks 
Close 
observation2 
Discontinue IMP2 
Discontinue 
IMP2 
 
 
 
 
↙ ↘ 
 
After at least 
2 weeks 
AST and ALT <3xULN 
 
AST or ALT ≥3xULN 
  
Re-escalate to next dose level for 
at least 2 weeks 
Weekly LFTs for the first 2 weeks 
(biweekly for the following 
weeks, or more frequently at 
investigator’s discretion) 
Repeat re-escalation to next 
higher dose level every 2 weeks 
(or longer at investigator’s 
discretion) if AST and ALT 
<3xULN 
Discontinue IMP 
Report SAE and complete liver event page for any of 
abnormalities listed below3: 
- 
AST/ALT increase ≥8xULN 
- 
AST/ALT increase ≥3xULN with signs of severe 
liver damage1  
 
1 Signs of severe liver damage: 
 
total bilirubin ≥1.5xULN OR international normalized ratio >1.5, and/or 
 
symptoms: appearance of fatigue, nausea, vomiting, right upper abdominal quadrant pain or tenderness, fever, rash and/or eosinophilia 
(>5%)  
2 Close observation recommendations:  
 
Monitor two to three times per week all of the following parameters: ALT, AST, alkaline phosphatase, total bilirubin, eosinophils, INR. 
If local regulations allow, home visits can be performed if subjects cannot come to the clinical study center. 
 
Frequency of retesting can be reduced to once a week or less if abnormalities stabilize or the IMP has been discontinued; however, 
monitoring might still be needed more frequently taking into consideration the standard of care and/or changes to this. 
 
Based upon Investigator’s discretion  gastroenterology or hepatology consultations, additional serology testing, imaging and pathology 
assessments may be required 
 
Re-query history of symptoms, prior and concurrent diseases, concomitant medication and non-prescription medicines, herbal, dietary 
supplements, alcohol use, recreational drug use, special diets. 
 
Rule out all of the following: acute viral hepatitis, auto-immune hepatitis, alcoholic hepatitis, non-alcoholic fatty hepatitis, 
hypoxic/ischemic hepatitis, biliary tract disease, and cholestasis. 
Re-query exposure to environmental chemical agents  

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3 The following steps (as defined in Section 4.5.4 should be followed: 
− 
The site should immediately contact the subject and require the subject to discontinue IMP immediately. The subject should be asked to 
return to the site within a 48-hour window from awareness of the result.  
− 
An assessment of other concomitant medications and SoC should be made. The investigator should consider whether it is in the best 
interest of the subject to interrupt concomitant medications and SOC treatment.  
− 
A detailed history including relevant information on (alcohol use, recreational drug use, supplement consumption, any herbal remedies, 
family history, sexual history, travel history, history of contact with a jaundiced subject, surgery, occupational history, blood 
transfusion, history of liver or allergic disease, and any other potential causes of a liver insult should be collected.  
− 
A detailed assessment of the subject’s clinical condition and repeat laboratory tests for LFT, including albumin, creatine kinase, total 
bilirubin (direct and indirect), GGT, INR and alkaline phosphatase should be done  
− 
Further testing for Hepatitis A, B, and C, and for autoimmune hepatitis should be done. Other causes of viral hepatitis (CMV or EBV 
etc) should be excluded.  Liver imaging should be considered.  
− 
Referral to a hepatologist or gastroenterologist should be considered. 
− 
All these cases should be reported as SAEs 
 

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APPENDIX 10: CONTRAINDICATIONS FOR 6MWT 
Absolute contraindications: 
- 
Unstable angina during the previous month [1] 
- 
Myocardial infarction during the previous month [1] 
- 
SpO2 measured by 
 <88% after 10 minutes of rest of breathing room air 
or at baseline oxygen flow rate [6] 
Relative contraindications [1]: 
- 
Resting heart rate >120 beats per minute 
- 
SBP >180 mmHg 
- 
DBP >100 mmHg 

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APPENDIX 11: DEFINITION OF ACUTE IPF EXACERBATION 
Definition and diagnostic criteria are defined as follows [4]: 
Definition: 
An acute, clinically significant respiratory deterioration characterized by evidence of new 
widespread alveolar abnormality. 
Diagnostic criteria: 
- 
Previous or concurrent diagnosis of IPF 
- 
Acute worsening or development of dyspnea typically < 1 month duration 
- 
Computed tomography with new bilateral ground-glass opacity and/or consolidation 
superimposed on a background pattern consistent with usual interstitial pneumonia 
pattern 
- 
Deterioration not fully explained by cardiac failure or fluid overload 
 
 
 

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Confidential Information 
 
SIGNATURE PAGE – SPONSOR 
 
Study Title: 
A Phase 3, randomized, double-blind, parallel-group, placebo-controlled 
multicenter study to evaluate the efficacy and safety of two doses of 
GLPG1690 in addition to local standard of care for minimum 52 weeks in 
subjects with idiopathic pulmonary fibrosis. 
 
This clinical study protocol has been reviewed and approved by the sponsor to ensure 
compliance with International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) guidelines for Good Clinical Practices (GCP) and 
applicable regulatory requirements. 
 
An electronic signature for the sponsor is provided at the end of the document.  
 
 MD 
  
  
Study Physician 
 Signature 
 Date 
 
 
 

Clinical Study Protocol (CSP) GLPG1690-CL-303 
Page 132/132 
 
 
 
Version 7.00, Final, 8-Jun-2020 
Confidential Information 
 
SIGNATURE PAGE – INVESTIGATOR 
 
Study Title: 
A Phase 3, randomized, double-blind, parallel-group, placebo-controlled 
multicenter study to evaluate the efficacy and safety of two doses of 
GLPG1690 in addition to local standard of care for minimum 52 weeks in 
subjects with idiopathic pulmonary fibrosis. 
 
I, the undersigned, have read this clinical study protocol and will conduct the study as 
described in compliance with the clinical study protocol, in accordance with International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 
(ICH) guidelines for Good Clinical Practices (GCP) and applicable regulatory requirements. 
 
 
 
  
  
Investigator Name 
 Signature 
 Date 
 

Signature Page for glpg1690-cl-303-protocol 11171
Signature Page for glpg1690-cl-303-protocol 11171
Approval
09-Jun-2020 10:10:44 GMT+0000