A Participant- and Investigator-blinded, Randomized, Placebo-controlled, Multicenter, Platform Study to Investigate Efficacy, Safety, and Tolerability of Various Single Treatments in Participants With Idiopathic Pulmonary Fibrosis
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
ADPT09 
Clinical Trial Protocol CADPT09A12201 / NCT05497284
A participant- and investigator-blinded, randomized, 
placebo-controlled, multicenter, platform study to 
investigate efficacy, safety, and tolerability of various 
single treatments in participants with idiopathic pulmonary 
fibrosis 
Document type: 
Amended Protocol Version 
EUDRACT number: 
2021-005066-17 
Version number: 
Name and address of the 
Sponsor: 
v05 (Clean) 
Novartis Pharma AG, Lichtstrasse 35, 4056 
Basel town, Switzerland 
Clinical Trial Phase: 
II 
Release date: 
09-Oct-2023
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 4.0 dated 15-Feb-2021 

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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 6 
List of figures ...................................................................................................................... 6 
List of abbreviations ............................................................................................................ 7 
Glossary of terms ............................................................................................................... 10 
Amendment 05 (09-Oct-2023) .......................................................................................... 13 
Amendment 04 (23-Aug-2023) ......................................................................................... 14 
Amendment 03 (24-Feb-2023) .......................................................................................... 15 
Amendment 02 (18-Jan-2023) ........................................................................................... 16 
Amendment 01 (04-Aug-2022) ......................................................................................... 17 
Protocol summary .............................................................................................................. 18 
1 
Introduction ....................................................................................................................... 21 
1.1 
Background ............................................................................................................ 21 
1.2 
Purpose .................................................................................................................. 22 
2 
Objectives, endpoints and estimands ................................................................................. 22 
2.1 
Primary estimands ................................................................................................. 23 
2.2 
Secondary estimands ............................................................................................. 23 
3 
Study design ...................................................................................................................... 24 
3.1 
End of Study Definition ......................................................................................... 25 
4 
Rationale ............................................................................................................................ 25 
4.1 
Rationale for study design ..................................................................................... 25 
4.1.1 
Rationale for choice of background therapy ......................................... 26 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 26 
4.3 
Rationale for choice of control drugs (comparator/placebo) ................................. 27 
4.4 
Purpose and timing of interim analyses ................................................................. 27 
4.5 
Risks and benefits .................................................................................................. 27 
4.5.1 
Blood sample volume ............................................................................ 29 
4.6 
Rationale for Public Health Emergency mitigation procedures ............................ 29 
5 
Study Population ............................................................................................................... 29 
5.1 
Inclusion criteria .................................................................................................... 30 
5.2 
Exclusion criteria ................................................................................................... 31 
6 
Treatment ........................................................................................................................... 33 
6.1 
Study treatment ...................................................................................................... 33 
6.1.1 
Investigational and control drugs .......................................................... 33 
6.1.2 
Additional study treatments .................................................................. 33 

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6.1.3 
Treatment arms/group ........................................................................... 33 
6.2 
Other treatment(s) .................................................................................................. 33 
6.2.1 
Concomitant therapy ............................................................................. 33 
6.2.2 
Prohibited medication ........................................................................... 34 
6.2.3 
Rescue medication ................................................................................ 34 
6.2.4 
Restriction for study participants .......................................................... 34 
6.3 
Preparation and dispensation ................................................................................. 34 
6.3.1 
Handling of study treatment and other treatment .................................. 35 
6.3.2 
Instruction for prescribing and taking study treatment ......................... 35 
6.4 
Participant numbering, treatment assignment, randomization .............................. 35 
6.4.1 
Participant numbering ........................................................................... 35 
6.4.2 
Treatment assignment, randomization .................................................. 36 
6.5 
Treatment blinding ................................................................................................. 37 
6.6 
Dose escalation and dose modification .................................................................. 38 
6.7 
Additional treatment guidance ............................................................................... 38 
6.7.1 
Treatment compliance ........................................................................... 38 
6.7.2 
Recommended treatment of adverse events .......................................... 39 
6.7.3 
Emergency breaking of assigned treatment code .................................. 40 
7 
Informed consent procedures ............................................................................................ 41 
8 
Visit schedule and assessments ......................................................................................... 42 
8.1 
Screening ............................................................................................................... 47 
8.1.1 
Eligibility screening .............................................................................. 47 
8.1.2 
Information to be collected on screening failures ................................. 47 
8.2 
Participant demographics/other baseline characteristics ....................................... 48 
8.3 
Efficacy .................................................................................................................. 48 
8.3.1 
Appropriateness of efficacy assessments .............................................. 48 
8.3.2 
6-Minute Walk Test .............................................................................. 48 
8.3.3 
Diffusing Capacity (DLCO) .................................................................. 49 
8.3.4 
High Resolution CT of Chest ................................................................ 49 
8.3.5 
Spirometry ............................................................................................. 49 
8.4 
Safety ..................................................................................................................... 49 
8.4.1 
Laboratory evaluations .......................................................................... 50 
8.4.2 
Electrocardiogram (ECG) ..................................................................... 52 
8.4.3 
Pregnancy and assessments of fertility ................................................. 52 
8.4.4 
Appropriateness of safety measurements .............................................. 53 
8.5 
Additional assessments .......................................................................................... 53 

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8.5.1 
Clinical Outcome Assessments (COAs) ............................................... 53 
8.5.2 
Pharmacokinetics .................................................................................. 54 
8.5.3 
Biomarkers ............................................................................................ 54 
8.5.4 
Immunogenicity .................................................................................... 56 
9 
Discontinuation and completion ........................................................................................ 57 
9.1 
Discontinuation from study treatment and from study .......................................... 57 
9.1.1 
Discontinuation from study treatment ................................................... 57 
9.1.2 
Discontinuation from study ................................................................... 58 
9.1.3 
Lost to follow-up ................................................................................... 58 
9.2 
Withdrawal of informed consent/Opposition to use data/biological samples ....... 58 
9.3 
Study stopping rules .............................................................................................. 59 
9.4 
Study completion and post-study treatment .......................................................... 60 
9.5 
Early study termination by the sponsor ................................................................. 60 
10 Safety monitoring, reporting and committees ................................................................... 60 
10.1 
Definition of adverse events and reporting requirements ...................................... 60 
10.1.1 
Adverse events ...................................................................................... 60 
10.1.2 
Serious adverse events .......................................................................... 62 
10.1.3 
SAE reporting........................................................................................ 63 
10.1.4 
Pregnancy reporting .............................................................................. 64 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 65 
10.2 
Additional Safety Monitoring ................................................................................ 65 
10.2.1 
Liver safety monitoring ......................................................................... 65 
10.2.2 
Renal safety monitoring ........................................................................ 66 
10.3 
Committees ............................................................................................................ 66 
10.3.1 
Data Monitoring Committee ................................................................. 66 
11 Data Collection and Database management ...................................................................... 67 
11.1 
Data collection ....................................................................................................... 67 
11.2 
Database management and quality control ............................................................ 67 
11.3 
Site monitoring ...................................................................................................... 68 
12 Data analysis and statistical methods ................................................................................ 68 
12.1 
Analysis sets .......................................................................................................... 69 
12.2 
Participant demographics and other baseline characteristics ................................. 69 
12.3 
Treatments ............................................................................................................. 69 
12.4 
Analysis supporting primary objectives ................................................................ 69 
12.4.1 
Definition of primary endpoint(s) ......................................................... 69 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 69 

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12.4.3 
Handling of intercurrent events of primary estimand ........................... 70 
12.4.4 
Handling of missing values not related to intercurrent event ............... 70 
12.4.5 
Sensitivity analyses ............................................................................... 70 
12.4.6 
Supplementary analysis ......................................................................... 71 
12.5 
Analysis supporting secondary objectives ............................................................. 71 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) .................................... 71 
12.5.2 
Safety endpoints .................................................................................... 72 
12.5.3 
Patient reported outcomes ..................................................................... 73 
12.6 
Analysis of exploratory endpoints ......................................................................... 73 
12.6.1 
Efficacy and/or Pharmacodynamic endpoint(s) .................................... 73 
12.6.2 
Pharmacokinetics .................................................................................. 74 
12.6.3 
PK/PD relationships .............................................................................. 74 
12.6.4 
Biomarkers ............................................................................................ 74 
12.6.5 
DNA ...................................................................................................... 75 
12.7 
Interim analyses ..................................................................................................... 75 
12.7.1 
Cohort Completion Analyses ................................................................ 75 
12.7.2 
Within each cohort ................................................................................ 75 
12.8 
Sample size calculation .......................................................................................... 76 
12.8.1 
Primary endpoint(s) ............................................................................... 76 
12.8.2 
Secondary endpoint(s) ........................................................................... 76 
13 Ethical considerations and administrative procedures ...................................................... 77 
13.1 
Regulatory and ethical compliance ........................................................................ 77 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 77 
13.3 
Publication of study protocol and results............................................................... 77 
13.4 
Quality Control and Quality Assurance ................................................................. 77 
13.5 
Participant Engagement ......................................................................................... 78 
14 Protocol adherence ............................................................................................................ 78 
14.1 
Protocol amendments ............................................................................................. 78 
15 References ......................................................................................................................... 79 
16 Appendices ........................................................................................................................ 81 
16.1 
Appendix 1: Liver event and laboratory trigger definitions & follow-up 
requirements .......................................................................................................... 81 
16.2 
Appendix 2: Specific Renal Alert Criteria and Actions and Event Follow-up ...... 84 
17 Cohort Specific Information .............................................................................................. 85 
17.1 
Cohort 1 LTP001 ................................................................................................... 85 
17.1.1 
Introduction ........................................................................................... 85 

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17.1.2 
Background ........................................................................................... 86 
17.1.3 
Study Treatment .................................................................................... 88 
17.1.4 
Specific Exclusion Criteria ................................................................... 89 
17.1.5 
Specific Restrictions for Study Participants .......................................... 90 
17.1.6 
Permitted concomitant therapy requiring caution and/or action ........... 90 
17.1.7 
 91 
17.1.8 
Pharmacokinetics .................................................................................. 93 
17.1.9 
Exploratory Biomarkers ........................................................................ 93 
17.1.10 
Specific Study Design Considerations .................................................. 94 
17.1.11 
Statistical considerations ....................................................................... 94 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 22 
Table 5-1 
 
 ....................... 30 
Table 6-1 
Blinding and unblinding plan ................................................................ 38 
Table 8-1 
Assessment Schedule ............................................................................ 44 
Table 8-2 
Safety Assessments ............................................................................... 50 
Table 8-3 
Laboratory Evaluations ......................................................................... 51 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 65 
Table 12-1 
Composition of the robust weakly informative prior for the placebo 
tie slope ................................................................................................. 70 
Table 16-1 
Liver event and laboratory trigger definitions ...................................... 81 
Table 16-2 
Follow up requirements for liver laboratory triggers - ALT, AST, 
TBL ....................................................................................................... 82 
Table 16-3 
Isolated total bilirubin elevation ............................................................ 83 
Table 16-4 
Specific Renal Alert Criteria and Actions ............................................. 84 
Table 17-1 
 88 
Table 17-2 
 90 
Table 17-3 
. 92 
Table 17-4 
LTP001 Specific Safety Assessments ................................................... 94 
Table 17-5 
Sensitivity of power to changes in assumptions for N=47 per group ... 94 
List of figures 
Figure 3-1 
Study design .......................................................................................... 24 
Figure 8-1 
Timing of study procedures .................................................................. 52 
Figure 17-1 
Cohort 1 Study Design .......................................................................... 85 
CCI
CCI
CCI
CCI
CCI

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List of abbreviations 
6MWT 
6 Minute Walk Test 
AE 
Adverse Event 
ALAT 
Latin American Thoracic Association 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ANOVA 
Analysis of variance 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
ATS 
American Thoracic Society 
BMI 
Body Mass Index 
CMO&PS 
Chief Medical Office and Patient Safety 
CO 
Country Organization 
COA 
Clinical Outcome Assessment 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CSR 
Clinical study report 
CTT 
Clinical Trial Team 
CV 
coefficient of variation 
DBP 
Diastolic Blood Pressure 
DIN 
Drug Inducted Nephrotoxicity 
DLCO 
Diffusing capacity for carbon monoxide 
DLT 
Dose Limiting Toxicity 
DMC 
Data Monitoring Committee 
DQF 
Data Query Form 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCOA 
Electronic Clinical Outcome Assessment 
EDC 
Electronic Data Capture 
EFS 
Event Free Survival 
ELISA 
Enzyme-linked immunosorbent assay 
ERS 
European Respiratory Society 
FDA 
Food and Drug Administration 
FEV1 
Forced expiratory volume in 1 second 
 
 
FSH 
Follicle Stimulating Hormone 
FVC 
Forced Vital Capacity 
FVC%p 
Forced Vital Capacity expressed in percent predicted 
GCP 
Good Clinical Practice 
GCS 
Global Clinical Supply 
GGT 
Gamma-glutamyl transferase 
GLDH 
Glutamate Dehydrogenase 
CCI

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h 
Hour 
HA 
Health authority 
HBcAb 
Hepatitis B core anti-body 
HBsAb 
Hepatitis B surface anti-body 
HBsAg 
Hepatitis B virus surface antigen 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human immunodeficiency virus 
HRCT 
High-resolution computed tomography 
HRQoL 
Health-Related Quality of Life 
IB 
Investigator's Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IMP 
Investigational Medicinal Product 
IN 
Investigator Notification 
INR 
International Normalized Ratio 
IP 
investigational product 
IPF 
Idiopathic Pulmonary Fibrosis 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IUD 
intrauterine device 
IUS 
intrauterine system 
JRS 
Japanese Respiratory Society 
K-BILD 
King’s Brief Interstitial Lung Disease 
L-IPF 
Living with IPF 
LCQ 
Leicester Cough Questionnaire 
LDH 
lactate dehydrogenase 
LFT 
Liver function test 
LLOQ 
lower limit of quantification 
LPLV 
Last Participant Last Visit 
MAD 
Multiple ascending dose 
MedDRA 
Medical dictionary for regulatory activities 
mg 
milligram(s) 
mL 
milliliter(s) 
 
 
PAH 
Pulmonary arterial hypertension 
PCR 
protein-creatinine ratio 
PD 
Pharmacodynamic(s) 
PFT 
Pulmonary function test 
PK 
Pharmacokinetic(s) 
CCI

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PoC 
Proof of Concept 
PRO 
Patient Reported Outcomes 
PT 
prothrombin time 
 
 
QMS 
Quality Management System 
QTcF 
QT interval corrected by Fridericia’s formula 
R-Scale for PF 
Raghu-Scale for Pulmonary Fibrosis 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SD 
standard deviation 
SpO2 
Oxygen saturation 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TBL 
Total Bilirubin 
UIP 
Usual interstitial pneumonia 
ULN 
upper limit of normal 
UTI 
Urinary Tract Infection 
WHO 
World Health Organization  
WoC 
Withdrawal of Consent 
WOCBP 
Women of child-bearing potential 
CCI

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Glossary of terms 
Additional treatment 
Medicinal products that may be used during the clinical trial as 
described in the protocol, but not as an investigational medicinal 
product (e.g. any background therapy) 
Assessment 
A procedure used to generate data required by the study 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), 
saliva, tissue, urine, stool, etc. taken from a study participant 
Clinical Outcome 
Assessment (COA) 
A measure that describes or reflects how a participant feels, functions, 
or survives 
Clinical Trial Team 
A group of people responsible for the planning, execution and reporting 
of all clinical trial activities. Examples of team members include the 
Study Lead, Medical Monitor, Trial Statistician etc. 
Coded Data 
Personal Data which has been de-identified by the investigative center 
team by replacing personal identifiers with a code. 
Cohort 
A group of individuals who share a common exposure, experience or 
characteristic, or a group of individuals followed-up or traced over time 
Control drug 
A study drug (active or placebo) used as a comparator to reduce 
assessment bias, preserve blinding of investigational drug, assess 
internal study validity, and/or evaluate comparative effects of the 
investigational drug 
Discontinuation from 
study 
Point/time when the participant permanently stops receiving the study 
treatment and further protocol required assessments or follow-up, for 
any reason. No specific request is made to stop the use of their 
samples or data. 
Discontinuation from 
study treatment 
Point/time when the participant permanently stops receiving the study 
treatment for any reason (prior to the planned completion of study drug 
administration, if any). Participant agrees to the other protocol required 
assessments including follow-up. No specific request is made to stop 
the use of their samples or data. 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g. 
100 mg once a day, 75 mg twice a day) 
Electronic Data Capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical 
study data using data collection systems, such as Web-based 
applications, interactive voice response systems and clinical laboratory 
interfaces. EDC includes the use of Electronic Case Report Forms 
(eCRFs) which are used to capture data transcribed from source 
data/documents used at the point of care 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last 
participant 
Enrollment 
Point/time of participant entry into the study at which informed consent 
must be obtained. The action of enrolling one or more participants 
Estimand  
As defined in the ICH E9(R1) addendum, estimand is a precise 
description of the treatment effect reflecting the clinical question posed 
by the trial objective. It summarizes at a population-level what the 
outcomes would be in the same participants under different treatment 
conditions being compared. Attributes of an estimand include the 
population, variable (or endpoint) and treatment of interest, as well as 
the specification of how the remaining intercurrent events are 
addressed and a population-level summary for the variable. 

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Intercurrent events 
Events occurring after treatment initiation that affect either the 
interpretation or the existence of the measurements associated with the 
clinical question of interest. 
Investigational drug/ 
treatment 
The drug whose properties are being tested in the study 
Investigational Product/ 
Investigational Medicinal 
Product 
A pharmaceutical form of an active ingredient or placebo being tested 
or used as a reference (such as an active comparator) in a clinical trial 
including a product with a marketing authorization when used or 
assembled (formulated or packaged) in a way difference from the 
approved form, or when used for an unapproved indication, or when 
used to gain further information about an approved used. 
Medication number 
A unique identifier on the label of medication kits 
Mis-randomized 
participants 
Mis-randomized participants are those who were not qualified for 
randomization and who did not take study treatment, but have been 
inadvertently randomized into the study or the participant allocated to 
an invalid stratification factor 
Other treatment 
Treatment that may be needed/allowed during the conduct of the study 
(i.e. concomitant or rescue therapy) 
Part  
A sub-division of a study used to evaluate specific objectives or contain 
different populations. For example, one study could contain a single 
dose part and a multiple dose part, or a part in participants with 
established disease and in those with newly diagnosed disease 
Participant 
A trial participant (can be a healthy volunteer or a patient). "Participant" 
terminology is used in the protocol whereas term "Subject" is used in 
data collection 
Participant number 
A unique number assigned to each participant upon signing the 
informed consent. This number is the definitive, unique identifier for the 
participant and should be used to identify the participant throughout the 
study for all data collected, sample labels, etc. 
Patient-Reported 
Outcome (PRO) 
A measurement based on a report that comes directly from the patient 
about the status of a participant's health condition without amendment 
or interpretation of the patient's report by a clinician or anyone else 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, 
Follow-up) which are described in the Protocol. Periods define the 
study phases and will be used in clinical trial database setup and 
eventually in analysis 
Personal data 
Participant information collected by the Investigator that is coded and 
transferred to Novartis for the purpose of the clinical trial. This data 
includes participant identifier information, study information and 
biological samples. 
Randomization 
The process of assigning trial participants to investigational drug or 
control/comparator drug using an element of chance to determine the 
assignments in order to reduce bias. 
Randomization number 
A unique identifier assigned to each randomized participant 
Re-screening 
If a participant fails the initial screening and is considered as a Screen 
Failure, he/she can be invited once for a new Screening visit after 
medical judgment and as specified by the protocol 
Remote 
Describes any trial activities performed at a location that is not the 
investigative site where the investigator will conduct the trial, but is for 
example a home or another appropriate location 

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Screen Failure 
A participant who did not meet one or more criteria that were required 
for participation in the study 
Source Data/Document 
Source data refers to the initial record, document, or primary location 
from where data comes. The data source can be a database, a 
dataset, a spreadsheet, or even hard-coded data, such as paper or 
eSource 
Start of the clinical trial 
The start of the clinical trial is defined as the signature of the informed 
consent by the first participant 
Study treatment 
Any drug or combination of drugs or intervention administered to the 
study participants as part of the required study procedures; includes 
investigational drug(s), control(s) or background therapy 
Treatment arm/group  
A treatment arm/group defines the dose and regimen or the 
combination and may consist of 1 or more cohorts. 
Treatment of interest 
The treatment of interest and, as appropriate, the alternative treatment 
to which comparison will be made. These might be individual 
interventions, combinations of interventions administered concurrently, 
e.g. as add-on to standard of care, or might consist of an overall 
regimen involving a complex sequence of interventions. This is the 
treatment of interest used in describing the related clinical question of 
interest, which might or might not be the same as the study treatment. 
Variable (or endpoint) 
The variable (or endpoint) to be obtained for each participant that is 
required to address the clinical question. The specification of the 
variable might include whether the participant experiences an 
intercurrent event. 
Withdrawal of study 
consent (WoC) / 
Opposition to use of data 
/biological samples 
Withdrawal of consent from the study occurs when the participant 
explicitly requests to stop use of their data and biological samples 
(opposition to use data and biological samples) AND no longer wishes 
to receive study treatment AND does not agree to further protocol 
required assessments. This request should be in writing (depending on 
local regulations) and recorded in the source documentation. 
Opposition to use data/biological samples occurs in the countries 
where collection and processing of personal data is justified by a 
different legal reason than consent. 

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Amendment 05 (09-Oct-2023) 
Amendment rationale 
The primary purpose of this amendment serves to remove a protocol allowed contraception 
method introduced inadvertently via Amendment 04 that is not considered highly effective as 
per CTFG guidelines. 
Changes to the protocol 
• Section 17.1.4 Specific Exclusion Criteria: Removed barrier methods of contraception 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation. 
 
 

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Amendment 04 (23-Aug-2023) 
Amendment rationale 
The primary purpose of this amendment serves to update for EU CTR submission and to add 
additional exclusionary considerations. 
Changes to the protocol 
• Section 4.6 Rationale for Public Health Emergency mitigation procedures: Updated to 
current Novartis language 
• Section 5.2 Exclusion Criteria: Additional considerations to Exclusion criterion 19 
• Section 6.3 Preparation and dispensation: Clarify drug accountability and reconciliation is 
recorded in IRT system 
• Section 10.1.1 Adverse Events: Updated to current Novartis language 
• Section 10.1.3 SAE reporting: Include European Clinical Trial Regulation 536/2014 
• Section 13.1 Regulatory and ethical compliance: Include European Clinical Trial 
Regulation 536/2014 
• Section 13.3 Publication of study protocol and results: Updated to current Novartis 
language and include CTIS public website 
• Section 17.1.4 Specific Exclusion Criteria: Updated to current Novartis language 
Other Changes 
• To correct inconsistencies, errors and typos 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation. 
 
 

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Amendment 03 (24-Feb-2023) 
Amendment rationale 
The primary purpose of this amendment serves to address German Health Authority feedback 
received by Novartis for the study protocol: 
• Justification for the treatment period of 26 weeks on LTP001 or placebo in Cohort 1. 
Changes to the protocol 
• Section 4.2 Rationale for dose/regimen and duration of treatment: Justification added for 
26 weeks of treatment 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation. 

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Amendment 02 (18-Jan-2023) 
Amendment rationale 
The primary purpose of this amendment serves to address feedback received by Novartis for 
the study protocol: 
• Participants with an ALT increase with bilirubin increase should discontinue study drug 
• Participants with a Grade 4 (>10 x ULN) isolated total bilirubin elevation should 
discontinue study drug 
• Sponsor should notify health authorities (HAs) and IRBs/ECs if the DMC 
recommendation to halt or terminate the study is not followed. 
Changes to the protocol 
• Table 8-1 (Assessment Schedule): Smoking History was added to Screening and Baseline. 
Footnote added to clarify ECG and DLCO will be performed on local site equipment. 
• Section 8.2 Participant demographics/other baseline characteristics: Smoking history 
added. 
• Section 10.3.1 Data Monitoring Committee: Clarify HAs and IRBs/ECs will be notified if 
recommendations are not followed. 
• Table 16-2 Follow-up requirements for liver laboratory triggers – ALT, AST, TBL: 
Participants with an ALT increase with bilirubin increase should discontinue study drug. 
• Table 16-3 Isolated total bilirubin elevation: Participants with a Grade 4 (>10 x ULN) 
isolated total bilirubin elevation should discontinue study drug. 
Other Changes 
• To correct inconsistencies, errors and typos 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation. 

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Amendment 01 (04-Aug-2022) 
Amendment rationale 
The purpose of this CADPT09A12201 protocol amendment is to address: 
i. The stratification of randomized participants by use of background therapy was outlined. 
ii. The Diffusing Capacity (DLCO) at Baseline was missed in the Assessment Schedule. 
The timing of this assessment was however included at all other parts of the initial 
protocol. 
iii. Clarification that additional participants may be enrolled if more than 15% of the planned, 
randomized participants have not completed the 26 weeks of treatment, following a DMC 
review for safety/ tolerability. 
Changes to the protocol 
• The Protocol summary was updated to reflect the modifications of the main document 
• Section 3 (Study Design) and Section 6.4.2 (Treatment assignment, randomization) 
See rationale i. Stratification 
• Section 8 (Assessment Schedule) 
See rationale ii. An X was added for the Diffusing Capacity (DLCO) Assessment at 
Baseline 
• Section 12.8 (Sample size calculation) 
See rationale iii. Additional patient enrollment 
Other changes 
• Section 5.2 Criteria 26 was shortened as already included in Criteria 25 
• Section 6.5 (Treatment Blinding) Clarification that unblinded interim reports are provided 
by an analysis team. 
• Section 12.4 (Analysis supporting primary objectives) 
• Standard of care was replaced by background therapy for better consistency and clarity. 
• To correct inconsistencies, errors, or typos 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation. 

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Protocol summary 
Protocol 
number 
CADPT09A12201 
Full Title 
A participant- and investigator-blinded, randomized, placebo-controlled, 
multicenter, platform study to investigate efficacy, safety, and tolerability of 
various single treatments in participants with idiopathic pulmonary fibrosis 
Brief title 
Study of efficacy and safety of various investigational products in participants 
with idiopathic pulmonary fibrosis 
Sponsor and 
Clinical Phase 
Novartis 
Phase II 
Investigation 
type 
Drug 
Study type 
Interventional 
Purpose 
The purpose of this proof-of-concept platform study is to determine whether 
selected systemic investigational products have an adequate clinical profile to 
support further clinical development in mild to moderate IPF. This platform 
design allows several investigational drugs to be tested in an adaptive way 
under the same conditions in one study. 
Primary 
Objective(s)  
The primary objective of this study is to assess the efficacy of the investigational 
products compared to placebo in participants with IPF measured by FVC 
expressed in percent predicted. 
Secondary 
Objectives 
• 
To assess the efficacy of the investigational products, compared to placebo 
in participants with IPF measured by FVC expressed in mL. 
• 
To assess the impact of the investigational products on “progression-free 
survival (PFS)” 
• 
To assess the incidence of absolute decline in FVC ≥10% predicted 
• 
To assess the impact of the investigational products on pulmonary 
physiology 
• 
To assess the impact of the investigational products on exercise capacity 
• 
To assess the impact of the investigational products on patient reported 
outcome 
• 
To assess the safety and tolerability of the investigational products in 
participants with mild to moderate IPF 
Study design 
This is a randomized, placebo-controlled, participant- and investigator-blinded 
platform study in participants with IPF. 
This study uses a platform type design to investigate multiple investigational 
products. Each investigational product and matching placebo entered into the 
trial at a given time will be considered a unique cohort. The decision to include 
future cohorts is not dependent on performance of prior products or cohorts. 
If multiple cohorts are open, participants will be allocated based on the cohort 
specific eligibility criteria. Should a participant be eligible for more than 
one cohort, they will be randomized to any suitable cohort. 
For each completed cohort, the data analysis will be performed upon final 
database lock for the cohort, and the results will be reported upon completion of 
each cohort in an end of cohort report. Each cohort in the study will undergo the 
same study evaluations and assessments. Each cohort will include a screening 

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period (Day -42 to Day -1), a treatment period of 26 weeks (Day 1 to Day 183), 
and a post treatment safety follow-up that is cohort specific. 
Within each cohort, randomization will be stratified by background therapy with 2 
levels: with background therapy (nintedanib or pirfenidone), or without 
background therapy.  
Rationale 
This study is designed to safely allow rapid and efficient screening of potentially 
efficacious investigational products in participants with IPF. 
Study 
population 
This study will be conducted in male and female participants with IPF who may 
or may not be receiving background therapy (either nintedanib or pirfenidone) 
and are at least 40 years of age. 
Key Inclusion 
criteria 
• 
Male and female participants at least 40 years of age 
• 
IPF diagnosed based on ATS/ERS/JRS/ALAT IPF 2018 modified guideline 
for diagnosis and management, within 5 years of screening 
• 
FVC ≥45% predicted at screening with no clinically significant deterioration 
between the screening visit and randomization, as determined by the 
investigator. 
• 
DLCO, corrected for hemoglobin, ≥25% predicted (inclusive) at screening 
with no clinically significant deterioration between the screening visit and 
randomization, as determined by the investigator. 
• 
Unlikely to die from cause other than IPF within the next 2 years, in the 
opinion of the investigator 
• 
Unlikely to undergo lung transplantation during this trial in the opinion of the 
investigator 
• 
If a participant is taking nintedanib or pirfenidone, they must be on a stable 
regimen for at least 8 weeks prior to randomization 
Key Exclusion 
criteria 
• 
Unable to perform PFTs, 6MWT or undergo HRCT procedure at time of 
screening 
• 
Peripheral capillary oxygen saturation (SpO2) <90% at rest (if on 
supplemental oxygen, must be ≤2 L/min at rest) 
• 
Airway obstruction (i.e., prebronchodilator FEV1/ FVC < 0.7) or evidence of 
a bronchodilator response at screening as defined by an absolute increase 
of ≥12% and an increase of ≥200ml in FEV1 or FVC, or both, after 
bronchodilator use, compared with the values before bronchodilator use at 
screening. 
• 
Emphysema >20% on screening HRCT as assessed visually by central 
reader. 
• 
Fibrosis <10% on screening HRCT as assessed visually by central reader. 
• 
Clinical diagnosis of any connective tissue disease (including but not limited 
to scleroderma, polymyositis/ dermatomyositis, systemic lupus 
erythematosus, and rheumatoid arthritis) or a diagnosis of interstitial 
pneumonia with autoimmune features as determined by the investigator 
applying the recent ERS/ ATS research statement 
• 
Other known causes of interstitial lung disease (e.g. domestic or 
occupational environmental exposures, drug toxicity) or another identifiable 
interstitial lung disease 
Study 
treatment 
A range of investigational products will be added to each cohort (placebo and 
active) that can enter the platform trial in a perpetual manner and at various 
unspecified time points. 

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Treatment of 
interest 
The randomized treatment (the investigational product or the control treatment) 
with or without the allowed concomitant medication for IPF. The dose of the 
allowed concomitant medication for IPF must remain stable during the trial. 
Efficacy 
assessments 
• 
Spirometry 
• 
Diffusion capacity for carbon monoxide (DLCO) 
• 
Six-Minute Walk Test (6MWT) 
• 
High resolution computed tomography (HRCT) 
• 
Investigator determined IPF Exacerbation 
Key safety 
assessments 
• 
Adverse event monitoring 
• 
Physical examinations 
• 
Monitoring of laboratory markers in blood and urine 
• 
ECGs 
• 
Vital signs 
Other 
assessments 
• 
Exploratory biomarkers 
• 
Pharmacokinetics 
• 
Pharmacogenetics 
• 
PROs 
• 
 
Data analysis 
For each completed cohort, the data analysis will be performed upon final 
database lock for the cohort, and the results will be reported upon completion of 
each cohort in an end of cohort report. Unless otherwise specified, placebo data 
from each previously completed cohort will be pooled with the current cohort 
placebo data. 
The treatment effect of the primary endpoint will be analyzed using a Bayesian 
random slope model to assess the difference in reduction rate (slope) between 
the treatment group and placebo group. The statistical model will include the 
intercept, time (as continuous variable), the interaction between treatment and 
time, the interaction of baseline FVC%p and time, and background therapy as 
fixed effect, and the intercept and slope of time for each participant as random 
effects. A robust weakly informative prior for the placebo time slope (based on 9 
phase II and III studies after 2012 with total of 492 participants) will be used in 
the Bayesian analysis. The Robustified informative prior for the change from 
baseline in FVC%p is comprised of 3 components of normal distributed random 
variables specified in Table 12-1. 
Key words 
Idiopathic pulmonary fibrosis, FVC, DLCO, 6-minute walk test, patient reported 
outcome, HRCT 
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1 
Introduction 
1.1 
Background 
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease, 
associated with a median survival of 2-5 years from initial diagnosis (Raghu et al 2011). 
IPF affects approximately 1.5 million patients worldwide. IPF is a disease of aging typically 
affecting patients older than 60 and not affecting patients younger than 40. Recently, nintedanib 
and pirfenidone were shown to slow the rate of IPF progression by targeting fibroblasts 
(King et al 2014, Richeldi et al 2014). However, it was shown that nintedanib and pirfenidone 
cannot halt the progression of IPF disease. Furthermore, neither nintedanib nor pirfenidone was 
able to demonstrate a significant impact on IPF mortality. Therefore, a considerable unmet 
medical need remains. 
Globally, North America and Europe have the highest incidence and prevalence of IPF 
(Hutchinson et al 2015). The incidence has been increasing steadily worldwide, in part due to 
an aging population. The annual incidence of IPF is currently between 3 and 9 per 
100,000 persons in Europe and North America. In a review of studies published between 1990 
and 2011, the prevalence of IPF ranged from 14.0 to 27.9 per 100,000 persons in the 
United States and from 1.25 to 23.4 per 100,000 persons in Europe (Nalysnyk et al 2012). 
Recent estimates from South Korea suggest the incidence and prevalence of IPF in Asia may 
be comparable to that of North America and Europe (Lee et al 2016). 
Clinical features of IPF include progressive cough, dyspnea, restrictive ventilatory defect, and 
progressive fibrosis and destruction of the lung parenchyma (Lynch et al 2016). The diagnosis 
is made in patients with the appropriate clinical features and the histologic pattern of usual 
interstitial pneumonia (UIP) (based on lung biopsy or high-resolution computed tomography 
(HRCT)).  Challenging factors for clinical management include older age, comorbid conditions, 
and acute unpredictable exacerbations.  Acute exacerbations of IPF are defined as sudden 
(typically less than 30 days onset) unexplained worsening of underlying disease, including new 
radiological infiltrates (based on HRCT) or UIP pattern.  The progressive deterioration of lung 
function results in respiratory failure. The prognosis following acute exacerbation and 
deterioration of lung function is poor, with 1-year and 5-year survival rates of 56.2% and 18.4% 
following acute exacerbation, which is considerably shorter than in IPF patients without acute 
exacerbation (Song et al 2011). 
The underlying pathophysiology of IPF remains unknown and likely involves a complex 
interplay of several key factors including environmental exposures, cellular susceptibilities and 
aberrant repair process. It is believed that recurrent micro injuries to the alveolar epithelium 
over time leads to a maladaptive repair process, which is characterized by epithelial cell death, 
senescence and inappropriate re-epithelization. In this setting, epithelial signaling leads to 
recruitment and activation of fibroblasts into myofibroblasts and recruitment of inflammatory 
cells. Additionally, failure of re-endothelization may lead to a dysfunctional alveolar-capillary 
barrier, inducing an additional pro-fibrotic response (du Bois 2010, Sgalla et al 2018). 
The ultimate proliferation and activation of fibroblasts and myofibroblasts and profibrotic 
immune cells leads to secretion of connective tissue matrix molecules, such as collagen, to 
replace the damaged tissue but also displaces healthy tissue leading to scarring and ultimately 
organ failure (du Bois 2010). 

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1.2 
Purpose 
The purpose of this proof-of-concept platform study is to determine whether selected systemic 
investigational products have an adequate clinical profile to support further clinical 
development in mild to moderate IPF. This proof-of-concept study is designed as a platform 
study. This platform design allows several investigational drugs to be tested in an adaptive way 
under the same conditions in one study. 
2 
Objectives, endpoints and estimands 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
• 
To assess the efficacy of the 
investigational products compared to 
placebo in participants with IPF 
• 
Change from baseline to end of 
treatment epoch (26 weeks of treatment) in Forced 
Vital Capacity (FVC) expressed in percent predicted 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
• 
To assess the efficacy of the 
investigational products, compared to 
placebo in participants with IPF 
• 
Change from baseline to end of 
treatment epoch (26 weeks of treatment) in Forced 
Vital Capacity (FVC) expressed in mL 
• 
To assess the impact of the 
investigational products on 
“progression-free survival (PFS)” 
• 
Time to progression as defined by a composite 
endpoint including any of the following events: 
• 
Absolute reduction from baseline of ≥10% 
predicted in FVC 
• 
Nonelective hospitalization for respiratory 
events 
• 
Lung Transplant 
• 
Death 
• 
To assess the incidence of absolute 
decline in FVC ≥10% predicted 
• 
Number of participants with absolute decline of 
≥10% predicted in FVC 
• 
To assess the impact of the 
investigational products 
on pulmonary physiology 
• 
Change from baseline to the end of treatment 
epoch (26 weeks of treatment) in DLCO absolute 
and percent predicted 
• 
To assess the impact of the 
investigational products on exercise 
capacity 
• 
Change from baseline to the end of treatment 
epoch (26 weeks of treatment) in 6-minute walk 
distance 
• 
To assess the impact of the 
investigational products on patient 
reported outcome 
• 
Change from baseline to the end of treatment 
epoch (26 weeks of treatment) in scores from the L-
IPF (Impacts and Symptoms Modules), K-BILD, 
Leicester cough, and R-Scale for PF questionnaires 
• 
To assess the safety and tolerability 
of the investigational products in 
participants with mild to moderate 
IPF 
• 
Adverse Events, physical examinations, labs, 
ECGs, vital signs 

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Objective(s) 
Endpoint(s) 
Exploratory objective(s) 
Endpoint(s) for exploratory objective(s) 
• 
To assess the impact of the 
investigational products on disease 
exacerbation. 
• 
IPF exacerbations or suspected exacerbations as 
determined by investigator and by using modified 
diagnostic criteria derived from Collard et al 2016 
and exacerbations as determined by the 
investigator as AEs/SAEs 
• 
To assess the impact of the 
investigational products on additional 
“progression-free survival (PFS)” 
analysis 
• 
Time to progression as defined by a composite 
endpoint including any of the following events: 
• 
Absolute reduction from baseline of ≥5% 
predicted in FVC 
• 
Non-elective hospitalization for respiratory 
events 
• 
Lung Transplant  
• 
Death 
• 
To evaluate change in extent of 
pulmonary fibrosis quantified by 
HRCT scan 
• 
Change in fibrosis from baseline to the end of 
treatment epoch (26 weeks of treatment) in 
quantitative high-resolution computed tomography 
(qHRCT) 
• 
To explore the impact of the 
investigational products on peripheral 
blood biomarkers 
• 
Change from baseline in soluble pharmacodynamic, 
target engagement and disease markers (may 
include but are not limited to: 
 
, and 
additional protein profiling) in the peripheral blood. 
• 
The pharmacokinetics of the 
investigational products after multiple 
doses will be assessed. 
• 
Appropriate PK parameters will be calculated where 
possible using non-compartmental analysis. 
These may include Tmax, Cmax, 
AUCs.  Population PK modelling may also be used 
for parameter estimation. 
• 
To explore the pharmacogenetics for 
the potential disease association or 
participant stratification 
• 
DNA analysis at baseline 
• 
 
 
 
 
 
 
2.1 
Primary estimands 
Not applicable 
2.2 
Secondary estimands 
Not applicable 
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3 
Study design 
This is a randomized, placebo-controlled, participant- and investigator-blinded platform study 
in participants with IPF. 
This study uses a platform type design to investigate “multiple targeted therapies in the context 
of a single disease in a perpetual manner” (Woodcock and LaVange 2017). Each investigational 
product and matching placebo entered the trial at a given time will be considered a unique 
cohort. The decision to include future cohorts is not dependent on performance of prior 
investigational products or cohorts. Each time a new cohort is introduced, investigational 
product specific information will be added to the protocol (Section 17) as a substantial 
amendment and submitted to Health Authorities and Ethical Committees, as required by local 
regulations. 
If multiple cohorts are open, participants will be allocated based on the cohort-specific 
eligibility criteria. Should a participant be eligible for more than one cohort, they will be 
randomized to any suitable cohort. 
Within each cohort, randomization will be stratified by background therapy with 2 levels: with 
background therapy (nintedanib or pirfenidone), or without background therapy. 
For each completed cohort, the data analysis will be performed upon final database lock for the 
cohort, and the results will be reported upon completion of each cohort in an end of cohort 
report. Each cohort in the study will undergo the same study evaluations and assessments. 
Each cohort will include a screening period (Day -42 to Day -1), a treatment period of 26 weeks 
(Day 1 to Day 183), and a post treatment safety follow-up that is cohort specific per Section 17. 
Figure 3-1 
Study design 
 

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3.1 
End of Study Definition 
Participant Completion 
A participant will be considered to have completed an intervention cohort if he or she has 
completed assessments through the final follow-up visit for that intervention cohort or 
discontinued earlier. 
Intervention Cohort Completion 
The end of the intervention cohort is defined as the date of the last visit for the last participant 
in that intervention cohort. 
Platform Study Completion 
The end of the platform study is defined as the date of the last visit of the last participant in the 
last cohort. 
4 
Rationale 
This study is designed to safely allow rapid and efficient screening of potentially efficacious 
investigational products in participants with IPF. The rationale for key aspects of the design is 
provided below. 
4.1 
Rationale for study design 
Novartis has several investigational products in its portfolio that are well situated to be studied 
in IPF. By applying a platform study protocol, Novartis can potentially assess multiple 
investigational products in a single trial. This is considered an efficient way to screen for 
investigational products that suggest high efficacy (Woodcock and LaVange 2017). 
Platform designs allow for the removal of investigational products based on emerging data and 
facilitates introduction of new investigational products by protocol amendment. Moreover, 
platform designs may allow for a reduced number of placebo participants as well as the potential 
to compare between cohorts and/or investigational products tested. Master protocol designs also 
offer potential advantages to participants in that they have the ability to use fewer participant 
resources, provide greater opportunity to be on active investigational product, and reach 
conclusions more quickly than traditional clinical trials. In this study, continuity of sites, 
including sites performing spirometry, a central imaging reader, and central labs across all 
cohorts and investigational products will specifically contribute to this master protocol 
advantage. In oncology, where master protocols are more frequently utilized, a review article 
suggested that master protocols also decrease heterogeneity of the study population, allowing 
for a more targeted approach to disease subtypes (Bitterman et al 2020). All these aspects of 
master protocol design, as well as an enriched ability to learn from parallel or prior cohorts 
within these trials, provide a strong rationale to apply this novel trial design to an area of high 
unmet need, such as IPF. 
Addition of new cohorts to the platform study occurs through protocol amendments. The core 
part of this platform protocol (Section 1 through Section 16) is not expected to significantly 

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change over time. New investigational product-specific information is added to Section 17 
using self-contained, cohort-specific modules in the form of amendments. This modular 
approach is expected to provide a consistent, reliable approach to adding new treatment cohorts. 
The cohort-specific modules (Section 17) will contain the mechanism of action, non-clinical 
information, proposed dose and dosing regimen, and rationale for each investigational product 
including anticipated safety, potential investigational product-investigational product 
interactions, unique inclusion or exclusion criteria, unique stopping rules or dose reduction 
criteria and other treatment specific information. 
4.1.1 
Rationale for choice of background therapy 
A current dose of ≤5 mg/day of prednisone or its equivalent is acceptable prior to 
randomization, and it is anticipated that the dose will remain stable throughout the participant’s 
enrollment. 
During a participant’s enrollment, pirfenidone or nintedanib may be taken as background 
therapy for IPF. The participant must be on a stable dose of either drug for at least 8 weeks prior 
to randomization. Both drugs are not to be used simultaneously. Participants should not 
initiate background therapy during the study. In cases where the investigator feels that 
background therapy is clinically indicated, this therapy can be started, but the initiation of 
background therapy will be considered a protocol deviation and possibly an outcome, such as 
an IPF exacerbation. Note, that a participant may continue in the study on their assigned 
treatment if background therapy is initiated, adjusted, or discontinued. 
While participating in the study, every effort should be made to maintain the participant on a 
stable dose of background therapy. However, background therapy dosing may be adjusted or 
discontinued by the physician responsible for the participant’s pulmonary care, with no dose to 
exceed the labeled maximum doses. 
In the event of an IPF exacerbation as determined by the investigator, if the investigator feels 
that additional therapy (other than pirfenidone or nintedanib) is clinically indicated, this therapy 
may be started and the medications, doses, and duration of treatment must be documented as 
concomitant medications. The participant may continue in the study. 
Participants should be instructed to continue the medications that they were receiving at 
enrollment and to avoid starting any new medications or herbal preparations during the study, 
since these may confound the results of the study. However, medically indicated medication or 
treatment should not be withheld. Participants should inform the investigator of any changes in 
the medications they are taking. 
4.2 
Rationale for dose/regimen and duration of treatment 
 
 
 
 
 
 
 
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Please refer to Section 17 (cohort-specific information) for a detailed rationale of each 
investigational product. 
In general, the dose of the investigational product to be studied will be chosen based on an 
evaluation of all available preclinical and/or clinical data to ensure target or pathway 
modulation and acceptable safety and tolerability and will be detailed in the corresponding 
Section 17. 
4.3 
Rationale for choice of control drugs (comparator/placebo) 
Matching placebo will be used in a blinded fashion within each cohort. The use of a placebo 
control is considered essential to ensure study validity and allow for appropriate assessments of 
safety and tolerability data as well as efficacy data (see Section 17 for investigational product 
specific treatment vs placebo randomization allocation). No active comparator is used in this 
study but use of background therapy is allowed (as noted above). 
4.4 
Purpose and timing of interim analyses 
For each investigational product, one or more interim analyses may be conducted, as 
appropriate, to support decision making concerning the sponsor's clinical development projects 
in general, or in case of any safety concerns. The first interim analysis will ideally occur when 
approximately half of the participants complete dosing per cohort. Additional modifications 
may be made per Section 17. Additional information is presented in Section 12.7. 
4.5 
Risks and benefits 
The risk to participants in this trial may be minimized by compliance with the eligibility criteria 
and study procedures, as well as close clinical monitoring. Refer to the Investigator's Brochure 
of each respective investigational product as identified per cohort. 
Women of child-bearing potential and sexually active males must be informed that taking the 
study treatment may involve unknown risks to the fetus if pregnancy were to occur during the 
study and agree that in order to participate in the study they must adhere to the contraception 
requirements outlined in the exclusion criteria. 
Detailed descriptions of the expected safety and tolerability characteristics of each IP can be 
found in Section 17. 
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The key risks associated with participation in CADPT09A12201, and their mitigation include: 
1. Two HRCTs will be performed in this study. Published dosimetry for HRCT shows a total 
maximal amount of radiation exposure per participant in the study will be approximately 
10 mSv (1000 mrem), less than the annual limits allowed in the EU and US, 20 and 
50 mSv, respectively. This amount of radiation is equivalent to approximately 3-5 years of 
exposure to background radiation (9 to 15 mSv, average yearly background dose is 
approximately 3 mSv in the US). For effective radiation doses between 3 mSv (300 mrem) 
and 50 mSv (5000 mrem), the risk is considered to be minimal. The radiation exposure in 
this study is aligned with other IRB approved respiratory trials, involves minimal risk, and 
is necessary to obtain the desired research information. 
2. Although this study excludes participants who are <40 years of age, there is a potential for 
enrolling women of childbearing potential and the treatments may involve unknown risks 
to the fetus if pregnancy were to occur during the study. This risk is mitigated by requiring 
proof the participant is not pregnant prior to start of treatment and requiring appropriate 
contraception during and for a suitable interval after treatment, as defined for each IP. 
See Section 17 for further details on each IP. 
Based on the above risk considerations, additional safety measures employed in 
CADPT09A12201 include, but are not limited to: 
• The study employs safety management measures, which are considered relevant and 
appropriate for this participant population and protocol to facilitate safe conduct of the 
study. 
• The study will only be conducted by investigators who have broad experience with 
participants who have IPF and concomitant medications. 
• Participants with severe IPF and high-expected mortality will not be enrolled. 
• Specific exclusion criteria prohibited medications and dietary restrictions will be put in 
place that are pertinent to each IP being tested. 
• This protocol pre-specifies both liver and renal events requiring intervention (Section 16.1 
and Section 16.2, respectively). 
• The study will also be monitored by an unblinded Data Monitoring Committee (DMC), 
which will provide an additional layer of oversight for safety events. For further details, 
please refer to Section 10.3.1. 
The key potential benefits expected to be associated with participation in the CADPT09A12201 
protocol include: 
1. Study participants may receive a potentially efficacious treatment; where currently, 
limited treatment options are available. 
2. Study participants will contribute to the potential identification of efficacious therapies for 
treatment of IPF, which has a high unmet medical need and increasing prevalence. 

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4.5.1 
Blood sample volume 
A volume smaller than a typical blood donation is planned to be collected over a period of 
32 weeks including screening and treatment periods and an additional variable safety follow-
up period defined in Section 17, from each participant as part of the study. The approximate 
volumes are mentioned in the ICF. Additional samples may be required for safety monitoring. 
Timings of blood sample collection are outlined in the assessment schedule (Table 8-1) and 
Section 17. 
A summary blood log is provided in the laboratory manual. Instructions for sample collection, 
processing, storage and shipment information are also available in the laboratory manual. 
See the Section 8.5.3.2 on the potential use of residual samples. 
4.6 
Rationale for Public Health Emergency mitigation procedures 
During a Public Health Emergency as declared by Local or Regional authorities e.g., pandemic, 
epidemic or natural disaster, mitigation procedures to ensure participant safety and trial integrity 
may be implemented. Notification of the public health emergency as declared by local or 
regional authorities should be discussed among investigators and Novartis. All procedures 
adapted to the situation must be submitted, if required as per local regulations, through a 
protocol amendment for approval by local or regional Health Authorities and Ethics 
Committees prior to implementation of mitigation procedures.. 
5 
Study Population 
This study will be conducted in participants with IPF who may or may not be receiving 
background therapy (either nintedanib or pirfenidone). 
The diagnostic criteria for IPF used in this protocol are derived from evidence-based guidelines 
developed by the American Thoracic Society/European Respiratory Society/Japanese 
Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) joint task 
force for the diagnosis and management of IPF (Raghu et al 2018a). 
The diagnosis of IPF requires radiographic and/or histopathologic evidence of UIP and 
exclusion of other causes of idiopathic interstitial pneumonia and interstitial lung diseases 
(e.g. occupational, or environmental exposures, drug toxicities, collagen vascular diseases). 
The ATS/ERS/JRS/ALAT joint task force concludes that, in the appropriate clinical setting, the 
diagnosis of IPF may be ascertained by HRCT alone if the HRCT image fulfills the criteria for 
“UIP pattern” or, in participants > 60 years old, a “probable UIP pattern” (i.e., surgical lung 
biopsy/cryobiopsy is not required). However, if the HRCT does not show a definitive UIP 
pattern or a probable UIP pattern in participants > 60 years old, then a surgical lung 
biopsy/cryobiopsy is necessary and specific combinations of the HRCT and histopathological 
criteria are used to determine the diagnosis of IPF (see Table 5-1). 

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Table 5-1 
 
 
5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all the following criteria: 
1. Written informed consent must be obtained before any assessment is performed. 
2. Male and female participants at least 40 years of age 
3. IPF diagnosed based on ATS/ERS/JRS/ALAT IPF 2018 modified guideline for diagnosis 
and management, within 5 years of screening (Modified Raghu et al 2018a, Table 5-1) 
(HRCT and surgical lung biopsy or cryobiopsy (if available) will be read by a central reader) 
(see text and Table 5-1 for more information on how such diagnoses will be made) 
4. FVC ≥45% predicted at screening with no clinically significant deterioration, as determined 
by investigator between the screening visit and randomization, as determined by the 
investigator. 
5. DLCO, corrected for hemoglobin, ≥25% predicted (inclusive) at screening with no 
clinically significant deterioration, as determined by investigator between the screening visit 
and randomization, as determined by the investigator. 
6. Unlikely to die from cause other than IPF within the next 2 years, in the opinion of 
the investigator 
7. Unlikely to undergo lung transplantation during this trial in the opinion of the investigator 
8. If a participant is taking nintedanib or pirfenidone, they must be on a stable regimen for at 
least 8 weeks prior to randomization  
9. Able to communicate well with the investigator, to understand and comply with 
the requirements of the study 
CCI
CCI

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5.2 
Exclusion criteria 
Participants meeting any of the following criteria are not eligible for inclusion in this study. 
1. Unable to perform PFTs, 6MWT or undergo HRCT procedure at time of screening 
2. Inability to comply with study requirements. 
3. Peripheral capillary oxygen saturation (SpO2) <90% at rest (if on supplemental oxygen, 
must be ≤2 L/min at rest) 
4. Airway obstruction (i.e., prebronchodilator FEV1/ FVC < 0.7) or evidence of a 
bronchodilator response at screening as defined by an absolute increase of ≥12% and an 
increase of ≥ 200ml in FEV1 or FVC, or both, after bronchodilator use, compared with the 
values before bronchodilator use at screening. 
5. Emphysema >20% on screening HRCT as assessed visually by central reader. 
6. Fibrosis <10% on screening HRCT as assessed visually by central reader. 
7. Clinical diagnosis of any connective tissue disease (including but not limited to 
scleroderma, polymyositis/ dermatomyositis, systemic lupus erythematosus, and 
rheumatoid arthritis) or a diagnosis of interstitial pneumonia with autoimmune features as 
determined by the investigator applying the recent ERS/ ATS research statement 
(Fischer et al 2015). Note: serological testing is not needed if not clinically indicated. 
8. Other known causes of interstitial lung disease (e.g. domestic or occupational environmental 
exposures, drug toxicity) or another identifiable interstitial lung disease 
9. Clinically diagnosed acute exacerbation of IPF (AE-IPF) or other significant clinical 
worsening within 3 months of randomization 
10. History of major organ, hematopoietic stem cell or bone marrow transplant 
11. History of hypersensitivity to the study drug or to drugs of similar chemical classes in the 
cohort the participant is to be randomized 
12. Serious local infection (e.g. cellulitis, abscess) or systemic infection that required 
hospitalization or was clinically significant in the opinion of the investigator, within 
3 months prior to screening. 
13. Fever (body temperature >38 degrees Celsius) or symptomatic viral or bacterial infection 
within 2 weeks prior to screening or randomization  
• A known or suspected symptomatic Covid diagnosis within 3 months of screening visit 
or prior to randomization 
14. History of primary or secondary immunodeficiency, including a positive human 
immunodeficiency virus (HIV) (enzyme-linked immunosorbent assay [ELISA] and western 
blot) test result 
15. Current hepatitis C infection (defined as positive HCV antibody and detectable HCV 
ribonucleic acid [RNA]). Participants with positive HCV antibody and undetectable HCV 
RNA are eligible to participate in the study. Current hepatitis B infection (defined as 
positive for hepatitis B surface antigen [HBsAg] or positive anti-HBc with a negative 
anti-HBs). Participants with immunity to hepatitis B from previous natural infection 
(defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination 
(defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to 
participate in the study. 

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16. History of malignancy of any organ system (other than completely excised, localized 
carcinoma of the skin such as basal cell or squamous cell carcinoma or in situ cervical 
cancer), treated or untreated, within the past 5 years of screening, regardless of whether 
there is evidence of local recurrence or metastases 
17. Significant cardiac disease (e.g. New York Heart Association Class 3 or 4; myocardial 
infarction within the past 6 months of screening; unstable angina; coronary angioplasty or 
coronary artery bypass graft within the past 6 months of screening; uncontrolled atrial or 
ventricular cardiac arrhythmias). 
18. Pulmonary hypertension requiring pharmacologic treatment. 
19. Any surgical, medical (e.g. uncontrolled hypertension, diabetes), psychiatric or additional 
physical condition that the investigator feels may jeopardize the participant in case of 
participation in this study.  The investigator should make this determination in consideration 
of the patient’s medical history and/or clinical or laboratory evidence of any of the 
following: 
• Moderate or severe hepatic failure (Child-Pugh classification stage B or C) 
• Significant renal impairment with an estimated glomerular filtration rate (eGFR) 
< 30 mL/min as calculated by the CKD-EPI formula 
21. Other unspecified reason that in the opinion of the investigator in consultation with the 
sponsor makes the participant unsuitable for enrollment 
22. Active drug or alcohol abuse (as defined by the investigator) within 3 months prior to 
screening. 
23. Use of any inhaled substance, including but not limited to tobacco or marijuana products 
and/ or the use of any electronic cigarette or vaping device, within 12 weeks prior to 
screening (note that respiratory inhalers or nebulizers for delivery of prescribed medication 
for pulmonary disease are allowed). 
24. Any one of the following screening values of complete blood count laboratory values: 
• Hemoglobin levels < 10.0 g/dL 
• Total leukocyte count < 3,000/μL 
• Neutrophils <1.5 x 103 /μL 
• Platelets <100.0 x 103 /μL 
• Total Bilirubin > 1.5 mg/dL (in the absence of known Gilbert's syndrome) 
• Aspartate transaminase (AST) or alanine transaminase (ALT) > 2X upper limit of 
normal 
25. Currently receiving high-dose corticosteroid, cytotoxic therapy (e.g. chlorambucil, 
azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for pulmonary 
hypertension (e.g. bosentan), unapproved (e.g. IFN-γ, penicillamine, cyclosporine, 
mycophenolate, N-acetylcysteine [may vary by country]) and/or investigational therapy or 
device for IPF or administration of such therapeutics within 5 half-lives of the IP prior to 
initial screening in this study. A current dose of ≤5 mg/day of prednisone or its equivalent 
is acceptable if the dose is expected to remain stable during the study. (Note: 
N-Acetylcysteine used to treat cough is permissible).  
26. Plan to enroll in another interventional trial while in this study 

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27. Blood donation of 1 unit (approximately 473mL) or more within 1 month prior to screening. 
28. Male or female planning a pregnancy during the duration of this study. A serum pregnancy 
test will be performed on all female participants of childbearing potential. 
29. Pregnant or nursing (lactating) women 
30. Elective surgery planned to take place during this trial (excluding diagnostic procedures 
such as colonoscopy, etc.) 
31. Women of child-bearing potential (WOCBP), defined as all women physiologically capable 
of becoming pregnant, unless they are using appropriate methods of contraception for 3 
months prior to screening, during dosing, and for a period after stopping of investigational 
medication (any treatment specific contraception requirements and changes to duration or 
if WOCBP cannot be enrolled at all are outlined in Section 17). 
6 
Treatment 
6.1 
Study treatment 
Details on the requirements for storage and management of study treatment, and instructions to 
be followed for participant numbering, prescribing/dispensing, and taking study treatment are 
outlined in Section 17. 
Refer to Section 17 for details of dosing and food intake, if relevant. 
6.1.1 
Investigational and control drugs 
Refer to cohort-specific information in Section 17. 
6.1.2 
Additional study treatments 
No other treatment beyond investigational drug and control drug are included in this trial. 
6.1.3 
Treatment arms/group 
Refer to cohort-specific information in Section 17 
6.2 
Other treatment(s) 
Refer to Section 17 for guidance for other treatments based on the specific IP/cohort. 
6.2.1 
Concomitant therapy 
All medications, procedures, and significant non-drug therapies (including physical therapy, 
blood transfusions, oxygen) administered after the participant was enrolled into the study must 
be recorded on the appropriate Case Report Forms. 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt, the investigator should contact the Novartis medical monitor before 
randomizing a participant or allowing a new medication to be started. If the participant is 
already enrolled, contact Novartis to determine if the participant should continue participation 
in the study. 

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6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
IP-specific permitted concomitant therapy is listed in Section 17 where applicable for each IP. 
6.2.2 
Prohibited medication 
Treatment-specific prohibited medications are provided in Section 17 for the individual 
IPs/cohorts. Any medications prohibited in the core protocol are listed in the core inclusion 
(Section 5.1) and exclusion (Section 5.2) criteria. Simultaneous use of pirfenidone and 
nintedanib is prohibited. 
Please refer to the respective cohort-specific information in Section 17 for additional 
restrictions, as applicable. 
6.2.3 
Rescue medication 
Treatment for an acute exacerbation is at the discretion of the investigator and medications 
(such as prednisone) can be freely initiated or increased at the investigator’s discretion. 
6.2.4 
Restriction for study participants 
For the duration of the study, participants should be informed and reminded of the restrictions 
outlined in the IP-specific Section 17 and within Section 6. 
6.2.4.1 
Dietary restrictions and smoking 
Participants must abstain from smoking or vaping any substances. 
Refer to cohort-specific information in Section 17 for any IP specific dietary restrictions. 
6.2.4.2 
Other restrictions 
No other restrictions apply. 
6.3 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under investigational 
and control drugs Section 6.1.1. 
A unique medication number is printed on the study medication label. 
Investigator staff will identify the study medication kits to dispense to the participant by 
contacting the IRT system and obtaining the medication number(s). Drug accountability and 
reconciliation data is recorded in the IRT system. 
As per Section 4.6, during a Public Health Emergency as declared by Local or Regional 
authorities (i.e. pandemic, epidemic or natural disaster), that limits or prevents on-site study 
visits, delivery of IMP directly to a participant's home may be permitted (if allowed by Local 
or Regional Health Authorities and Ethics Committees as appropriate) in the event the 
investigator has decided that an on-site visit by the participant is no longer appropriate or 
possible, and that it is in the interest of the participant's health to administer the study treatment 
even without performing an on-site visit. The dispatch of IMP from the site to the participant’s 
home remains under the accountability of the investigator. Refer to Section 17 for details. 

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6.3.1 
Handling of study treatment and other treatment 
6.3.1.1 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis CO Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number. 
The investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
field monitors during site or remote monitoring visits, and at the completion of the trial. 
The site may destroy and document destruction of unused study treatment, drug labels and 
packaging as appropriate in compliance with site processes, monitoring processes, and per local 
regulation/guidelines. Otherwise, the investigator will return all unused study treatment, 
packaging, drug labels, and a copy of the completed drug accountability log to the Novartis 
monitor or to the Novartis address provided in the investigator folder at each site. 
6.3.1.2 
Handling of other treatment 
It should be checked at each visit that other concomitant IPF specific therapy has been kept 
stable as specified in the study eligibility criteria (Section 5) and in Section 6.2.1. 
6.3.2 
Instruction for prescribing and taking study treatment 
Refer to cohort-specific information in Section 17. 
6.4 
Participant numbering, treatment assignment, randomization 
6.4.1 
Participant numbering 
Each participant is identified in the study by a Participant Number, that is assigned when the 
participant is enrolled for screening and is retained for the participant throughout his/her 
participation in the trial. A new Participant No. will be assigned if the participant is re-screened. 
The Participant No. consists of the Center Number (Center No.) (as assigned by Novartis to the 
investigative site) with a sequential participant number suffixed to it, so that each participant’s 
participation is numbered uniquely across the entire database. Upon signing the informed 
consent form, the participant is assigned to the next sequential Participant No. available. 
A new informed consent form will need to be signed if the investigator chooses to re-screen the 
participant after a participant has screen failed, and the participant will be assigned a new 
Participant No. The original Participant No must be added in the respective eCRF to link the 
two subjects for reporting and validation purposes. 

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Participants may join subsequent cohorts. Participants will sign a new informed consent form 
and will screen per protocol. Participants will be assigned to the next sequential Participant No. 
available. The original Participant No must be added in the respective eCRF to link the 
two subjects for reporting and validation purposes. 
6.4.2 
Treatment assignment, randomization 
The following methods have been used to minimize bias in the assignment. 
Participants will be randomized in two-stages. Participants will be randomized to a cohort first 
and then randomized to a treatment arm (i.e. investigational drug or placebo) within a cohort. 
Participants eligible for only one cohort will be assigned directly to that cohort. 
Randomization to any cohort will follow dynamic allocation ratio which allows flexibility to 
allocate participants based on weighted probabilities assigned to the cohorts. Allocation to 
treatment arms within a cohort will initiate with a pre-specified ratio for that particular cohort 
(e.g. 1:1, 2:1, 3:1) that could vary at any time during the study. Any changes in randomization 
ratio will be updated in the ICF. This randomization scheme allows the Sponsor to maintain at 
least 1:1 ratio for placebo vs. treatment for any given cohort after sharing placebo subjects 
across cohorts. 
Randomization will be stratified by background therapy with 2 levels: with background therapy 
(nintedanib or pirfenidone), or without background therapy. Note that nintedanib and 
pirfenidone are the only IPF treatments permitted outside of study treatment assignment. 
The investigator or his/her delegate will contact the IRT after confirming that the participant 
fulfills all the inclusion/exclusion criteria. The IRT will assign a randomization number to the 
participant, which will be used to link the participant to a treatment arm and will specify a 
unique medication number for the first package of study treatment to be dispensed to the 
participant. 
For any prematurely terminated cohort not due to safety, all ongoing participants in the 
treatment arms in this cohort may be discontinued and not replaced. For any prematurely 
terminated cohort due to safety, all ongoing participants in the treatment arms in this cohort will 
be discontinued and not be replaced. Enrollment into any prematurely terminated cohort will be 
stopped. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from participants and investigator staff. 
A participant randomization list will be produced by the IRT provider using a validated system 
that automates the random assignment of participant numbers to randomization numbers. 
These randomization numbers are linked to the different treatment arms, which in turn are 
linked to medication numbers. A separate medication list will be produced by or under the 
responsibility of Novartis Global Clinical Supply (GCS) using a validated system that 
automates the random assignment of medication numbers to packs containing the study 
treatment. 
Details of the randomization requirements will be documented in randomization requirement 
specification document. The randomization scheme for participants will be reviewed and 
approved by a member of the Randomization Office. 

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6.5 
Treatment blinding 
Participants and the investigator staff (except as outlined below) will remain blind to the identity 
of the treatment from the time of randomization until cohort database lock. However, both 
participant and investigator will know to which cohort the participant has been assigned. 
Unblinding a single participant at site for safety reasons (necessary for participant management) 
will occur via an emergency system in place at the site. As a result, the participant should be 
discontinued from the study treatment. 
The randomization codes associated with participants from whom PK samples are taken will be 
disclosed to PK analysts who will keep PK results confidential until database lock. 
The following methods will be used to maintain the blind: 
(1) Randomization data will be kept strictly confidential until the time of cohort database lock 
and will not be accessible by anyone else involved in the study with the following exceptions: 
• an independent analysis team who needs to prepare the safety interim analysis reports for 
the DMC 
• the bioanalyst for PK analysis (to avoid the unnecessary analysis of placebo samples) 
(2) data with unblinding potential, (such as applicable PK concentrations and biomarkers) 
collected after the randomization visit, will be kept blind until the time of cohort database lock. 
At the time of safety review/interim analysis, the DMC will review unblinded interim reports 
created by an analysis team. More details will be provided in the DMC charter. 
At the time of interim analysis for efficacy, the Novartis Clinical Trial Team will create and 
review unblinded interim reports. 
The study statistician will be able to access the randomization list for interim analyses and is 
allowed to share unblinded information with the rest of the clinical team as appropriate for 
internal decision purposes, as outlined in Table 6-1. For example, unblinded summaries and 
unblinded individual data can be shared with the team for interim analyses. 
Study programmers and other personnel involved in study data analysis (e.g. biomarker expert) 
are allowed to access treatment assignment information for the purpose of conducting interim 
analyses. 
The clinical trial team is allowed to share unblinded results with other sponsor staff 
(e.g. decision boards) as required for internal decision making on the study or the project at the 
time of interim analyses while the study is ongoing. 
All unblinded personnel will otherwise keep randomization lists and data or information that 
could unblind other study team members confidential and secure except as described above. 
Following cohort database lock for each investigational product, all sponsor roles may be 
considered unblinded. 

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Table 6-1 
Blinding and unblinding plan 
Role 
Time or Event 
Randomization 
list generated 
Treatment 
allocation & 
dosing 
Safety event 
(single 
subject 
unblinded) 
Interim 
Analysis/ dose 
escalation/ 
safety review 
Subjects/Patients 
B 
B 
UI 
B 
Site Staff 
B 
B 
UI 
B 
Unblinded site staff, e.g. 
pharmacy staff 
B 
UI 
UI 
UI 
Randomization Office 
UI 
UI 
UI 
UI 
Unblinded Sponsor staff, e.g. for 
study treatment re-supply, 
unblinded monitor(s), sample 
analyst(s) 
B 
UI 
UI 
UI 
Independent 
Statistician/statistical 
programmer/ data analysts (e.g. 
biomarker, PK) 
B 
B 
UI 
UI 
All other Sponsor staff not 
identified above (i.e. project 
team, management & decision 
boards, support functions) 
B 
B 
UI 
UI 
Independent committees used 
for assessing interim results, if 
required (e.g. DMC) 
B 
B 
UI 
UI 
B Complete blinded 
UI Unblinded to individual participant treatment codes 
6.6 
Dose escalation and dose modification 
Investigational or other study treatment dose adjustments and/or interruptions are only 
permitted as described in Section 17. 
6.7 
Additional treatment guidance 
6.7.1 
Treatment compliance 
The investigator must promote compliance by instructing the participant to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the validity of 
the study. The participant must also be instructed to contact the investigator if he/she is unable 
for any reason to take the study treatment as prescribed. Compliance will be assessed by the 
investigator and/or study personnel at each visit and information provided by the participant. 
This information should be captured in the source document at each visit. All study treatment 
dispensed and returned must be recorded in the Drug Accountability Log. 
Pharmacokinetic parameters (measures of treatment exposure) will be determined in all 
participants, as detailed in Section 17. 

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6.7.2 
Recommended treatment of adverse events 
Adverse events should be treated as per standard of care. Medication used to treat AEs must be 
recorded on the appropriate CRF. 
6.7.2.1 
Acute Exacerbations of IPF 
A participant who experiences a worsening of respiratory status at any time during the study 
should immediately contact their treating physician. The participant should also notify the 
investigator (if different than the treating physician) to schedule the IPF Exacerbation Visit as 
soon as possible so that the investigator may assess and confirm the IPF exacerbation. 
Should the participant be unable to come to the clinic for the IPF Exacerbation Visit, the 
investigator should attempt to complete the investigator’s determination of IPF exacerbation 
(see Section 6.7.2.2) as soon as possible. 
The IPF Exacerbation Visit should include the following per Table 8-1: 
• Physical examination 
• Vital signs 
• Oxygen saturation 
• Spirometry 
• DLCO 
• Imaging studies (chest X-ray or HRCT) if not performed at another facility 
• Investigator's determination of IPF exacerbation (see Section 6.7.2.2) 
This visit may also include the following at the investigator's discretion: 
• ECG 
• Clinical laboratory tests (hematology, blood chemistry, and urinalysis) 
• Other tests or evaluations at the discretion of the investigator   
Note:  If an IPF exacerbation is suspected at the time of a scheduled visit or is to be evaluated 
at a scheduled visit, the IPF exacerbation assessments listed above must be performed at the 
scheduled visit if not already included. 
A participant who is evaluated, treated, or hospitalized at a facility other than the study site 
should contact the study site following that visit to determine if the participant should come in 
for a stand‑alone IPF Exacerbation Visit or have additional IPF exacerbation assessments 
during a routine, scheduled study visit. In addition, if a participant was hospitalized or had IPF 
exacerbation assessments at another facility, study site personnel should make every effort to 
obtain sufficient medical records to determine the following: 
• Possible triggers or causes of the event. 
• The results of relevant tests and assessments, including but not limited to:  
• Detailed radiography reports and copies of images of all radiographic 
• examinations (e.g. chest X-ray or HRCT scan) for submission to the central imaging 
vendor. 
• Spirometry, body plethysmography (lung volume), and/or DLCO testing reports. 
• Descriptions of the severity and duration of the event. 

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• Details of the medical treatment provided, including relevant medications and other major 
elements of the clinical management. 
The participant’s response to the treatment and clinical status at the time of discharge. 
6.7.2.2 
Determination of IPF Exacerbation 
Based on the results obtained from evaluations at the IPF Exacerbation Visit and/or the records 
obtained from a visit to another facility (if applicable), the investigator will determine whether 
an IPF exacerbation or suspected IPF exacerbation has occurred. The investigator will assess 
the occurrence of IPF exacerbation using the revised diagnostic criteria for IPF exacerbation 
and suspected IPF exacerbation of the international working group report in 2016 
(Collard et al 2016), as follows: 
• 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 UIP pattern. 
• Deterioration not fully explained by cardiac failure or fluid overload. 
Note: Events that are clinically considered to meet the definition of acute exacerbation of IPF 
but fail to meet all diagnostic criteria owing to missing computed tomography data should be 
termed “suspected acute exacerbations.” 
The investigator’s determination of IPF exacerbation based on the 2016 definition should be 
documented on the appropriate CRF. 
As noted, treatment for an acute exacerbation is at the discretion of the investigator and 
medications (such as prednisone) can be freely initiated or increased at the investigator’s 
discretion. 
6.7.3 
Emergency breaking of assigned treatment code 
Emergency code breaks must only be undertaken when it is required to in order to treat the 
participant safely. 
Most often, discontinuation from study treatment and knowledge of the possible treatment 
assignments are sufficient to treat a study participant who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
investigator contacts the system to break a treatment code for a participant, he/she must provide 
the requested participant identifying information and confirm the necessity to break the 
treatment code for the participant. The investigator will then receive details of the 
investigational drug treatment for the specified participant and a fax or email confirming this 
information. The system will automatically inform the Novartis monitor for the site and the 
study team that the code has been broken. 

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It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency. The investigator 
will provide: 
• protocol number 
• name (if available) 
• participant number 
In addition, oral and written information to the participant must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that unblinding 
can be performed at any time. 
After an emergency break, the participant will not be allowed to continue treatment in their 
current cohort. The participant should still be followed for safety. 
7 
Informed consent procedures 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation) IRB/IEC-approved informed consent. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all of 
the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the participant source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent form 
that complies with the ICH E6 GCP guidelines and regulatory requirements and is considered 
appropriate for this study. Any changes to the proposed consent form suggested by the 
investigator must be agreed by Novartis before submission to the IRB/IEC. 
Information about common side effects already known about the investigational product can be 
found in the Investigator's Brochure (IB). This information will be included in the participant 
informed consent and should be discussed with the participant during the study as needed. 
Any new information regarding the safety profile of the investigational drug that is identified 
between IB updates will be communicated as appropriate, for example, via an investigator 
notification or an aggregate safety finding. New information might require an update to the 
informed consent and then must be discussed with the participant. 
The following informed consents are included in this study: 
• Main study consent, which also includes:  
• A subsection that requires a separate signature for the ‘Optional Consent for 
Additional Research’ to allow future research on data/samples collected during this 
study 
• As applicable, Pregnancy Outcomes Reporting Consent for female participants or the 
female partners of any male participants who took study treatment 
• Optional Genetics Consent to provide a DNA sample for exploratory DNA studies 
Women of childbearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order 
to participate in the study, they must adhere to the contraception requirements. 

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Male participants must be informed that if a female partner becomes pregnant while he is 
enrolled in the study, contact with the female partner will be attempted to request her consent 
to collect pregnancy outcome information. 
The study includes an optional DNA component which requires a separate signature if the 
participant agrees to participate. It is required as part of this protocol that the investigator 
presents this option to the participants, as permitted by local governing regulations. The process 
for obtaining consent should be the same as described above for the main informed consent. 
Declining to participate in these optional assessments (DNA) will in no way affect the 
participant’s ability to join the main research study. 
A copy of the approved version of all consent forms must be provided to Novartis after IRB/IEC 
approval. 
As per Section 4.6, during a Public Health emergency as declared by Local or Regional 
authorities i.e. pandemic, epidemic or natural disaster, that may challenge the ability to obtain 
a standard written informed consent due to limits that prevent an on-site visit, the investigator 
may conduct the informed consent discussion remotely (e.g. telephone, videoconference) if 
allowable by a local Health Authority. 
Guidance issued by local regulatory bodies on this aspect prevail and must be implemented and 
appropriately documented (e.g. the presence of an impartial witness, sign/dating separate ICFs 
by trial participant and person obtaining informed consent, etc.). 
8 
Visit schedule and assessments 
The Assessment Schedule (Table 8-1) lists all the assessments when they are performed. 
All data obtained from these assessments must be supported in the participant’s source 
documentation. 
Participants should be seen for all visits/assessments as outlined in the assessment schedule 
(Table 8-1) or as close to the designated day/time as possible. Missed or rescheduled visits 
should not lead to automatic discontinuation. 
Participants who discontinue study treatment must return for an End of Treatment visit as soon 
as possible, but within 4 weeks after discontinuation of treatment, as outlined in Section 9.1.1. 
If a participant is discontinued from the study, an End of Treatment visit will be scheduled or 
performed as soon as possible but within 4 weeks, as outlined in Section 9.1.2. If a participant 
withdraws their consent/opposes the use of their data/biological samples, an End of Treatment 
visit may be scheduled or performed as soon as possible but within 4 weeks, if the participant 
agrees. 
At this final visit, all dispensed investigational product should be reconciled, and the adverse 
event and concomitant medications not previously reported must be recorded on the CRF. 
The “X” in the table denotes the assessments to be recorded in the clinical database or received 
electronically from a vendor. The “S” in the table denotes the assessments that are only in the 
participant’s source documentation and do not need to be recorded in the clinical database. 

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When the following assessments are scheduled to be performed at the same time point, the order 
of priority will be as follows: 
The 6MWT must be performed after all ECGs, PFTs and PROs have been completed. 
As per Section 4.6, during a Public Health Emergency as declared by Local or Regional 
authorities (i.e. pandemic, epidemic, or natural disaster) that limits or prevents on-site study 
visits, alternative methods of providing continuing care may be implemented by the investigator 
as the situation dictates. If allowable by a local Health Authority and depending on operational 
capabilities, phone calls, virtual contacts (e.g. tele consult) or visits by site staff/ home nursing 
staff to the participant´s home, can replace on-site study visits, for the duration of the disruption 
until it is safe for the participant to visit the site again.

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Table 8-1 
Assessment Schedule 
Period Screening 
Treatment 
IPF Exacerbation Post-Treatment Follow-Up 
Visit Name Screening Baseline/Treatment 
Treatment 
EOT1 
Exacerbation 
Follow-Up 
Days -42 to -1 
1 
29 
±3 
57 
±3 
85 
±3 
113 
±3 
141 
±3 
183 
±5 
1 to EOS 
See Section 17 
Informed consent 
X 
  
  
  
  
  
  
  
  
  
Genetic consent 
X 
  
  
  
  
  
  
  
  
  
Inclusion / Exclusion 
criteria 
X 
  
  
  
  
  
  
  
  
  
Demography 
X 
  
  
  
  
  
  
  
  
  
Medical 
history/current 
medical conditions 
X 
X2 
  
  
  
  
  
  
  
  
Smoking history 
X 
X2 
 
 
 
 
 
 
 
 
Hepatitis screen 
S 
  
  
  
  
  
  
  
  
  
HIV screen 
S 
  
  
  
  
  
  
  
  
  
Pregnancy and 
assessments of 
fertility3 
S 
S 
S 
S 
S 
S 
S 
S 
  
S 
Body Height 
X 
  
  
  
  
  
  
X 
  
  
Body Weight4 
X 
  
  
  
  
  
  
X 
  
  
Physical 
Examination 
S 
S 
  
  
  
  
  
S 
S 
  
Limited Physical 
Examination5 
  
  
S 
S 
S 
S 
S 
  
  
S 
Body Temperature 
X 
  
  
  
  
  
  
  
X 
  
Blood Pressure, 
Oxygen Saturation 
and Pulse Rate 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Electrocardiogram 
(ECG)6 
X 
X 
  
  
X 
  
  
X 
X 
  

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Period Screening 
Treatment 
IPF Exacerbation Post-Treatment Follow-Up 
Visit Name Screening Baseline/Treatment 
Treatment 
EOT1 
Exacerbation 
Follow-Up 
Days -42 to -1 
1 
29 
±3 
57 
±3 
85 
±3 
113 
±3 
141 
±3 
183 
±5 
1 to EOS 
See Section 17 
Spirometry7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Diffusing Capacity 
(DLCO)6 
X 
X 
 
  
X 
  
  
X 
X 
  
High Resolution CT 
of Chest 
X 
  
  
  
  
  
  
X 
X 
  
6-Minute Walk Test8 
  
X 
  
  
X 
  
  
X 
  
  
Urinalysis 
X 
X 
  
  
  
  
  
  
  
  
Clinical Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation Panel 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cohort Specific 
Assessments 
X9 
X9 
X9 
X9 
X9 
X9 
X9 
X9 
X9 
X9 
PK/PD/Biomarkers10 
  
X11 
X11 
X11 
X11 
X11 
X11 
X11 
  
  
Exploratory DNA 
Sampling 
(optional)12 
  
X 
  
  
  
  
  
  
  
  
Drug dispensation 
  
X13 
X13 
X13 
X13 
X13 
X13 
  
  
  
Drug administration 
record 
  
  
X 
X 
X 
X 
X 
X 
  
  
L-IPF14 
  
X 
  
  
X 
  
  
X 
  
  
R-Scale for PF 
  
X 
  
  
X 
  
  
X 
  
  
K-BILD 
  
X 
  
  
X 
  
  
X 
  
  
Leicester Cough 
  
X 
  
  
X 
  
  
X 
  
  
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI

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Period Screening 
Treatment 
IPF Exacerbation Post-Treatment Follow-Up 
Visit Name Screening Baseline/Treatment 
Treatment 
EOT1 
Exacerbation 
Follow-Up 
Days -42 to -1 
1 
29 
±3 
57 
±3 
85 
±3 
113 
±3 
141 
±3 
183 
±5 
1 to EOS 
See Section 17 
Study completion 
information 
  
  
  
  
  
  
  
  
  
X 
Adverse 
Events/Serious 
Adverse Events 
As 
Required 
As Required 
As 
Required 
As 
Required 
As 
Required 
As 
Required 
As 
Required 
As 
Required 
As required 
As required 
X Assessment to be recorded in the clinical database or received electronically from a vendor 
S Assessment to be recorded in the source documentation only 
1 If study treatment is permanently discontinued prior to the end of the Treatment Period, an Early EoT visit will occur as soon as possible, but within 4 weeks. 
All assessments planned for the Day 183 visit except for the HRCT scan will be performed (see Section 9.1.1 for details). If a subject is withdrawn from the study prior to 
the end of the Treatment Period, an Early EoT visit will occur as soon as possible, but within 4 weeks. All assessments planned for the Day 183 visit will be performed 
except HRCT. If early EOT falls on or after Day 85 visit, HRCT should also be performed (see Section 9.1.2 for details). 
2 To be reconfirmed at randomization 
3 As required. Women of childbearing potential must have serum pregnancy test at screening and this test must be performed within 7 days prior to dosing. 
Subsequent testing may be urine (see Section 8.4 Safety for additional information).  
4 See Section 17 for additional cohort assessments, if needed 
5 Cardiac and Pulmonary exams must be performed. Symptom driven for all other organ systems 
6 ECG and DLCO will be performed using local site equipment 
7 Spirometry at screening visit will include Bronchodilator response. 
8 The 6MWT must be performed after all ECGs, PFTs and PROs have been completed.  Each 6MWT consists of 2 separate walks. 
9 See Section 17 for specific assessments 
10 PK samples may be collected at unscheduled times 
11 See Section 17 for specific time point for study drug arm 
12 Genetic research ICF must be obtained before optional DNA sampling. This optional sample can be collected anytime on Day 1 visit or thereafter. 
13 See Section 17 for study drug administration 
14 Impacts and Symptoms Modules 

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8.1 
Screening 
It is permissible to re-screen a participant if the participant fails the initial screening for a 
cohort, if deemed feasible or necessary by the study site investigator. Participants who do 
not meet the IPF diagnosis inclusion criteria should not be re-screened or screened for 
subsequent cohorts. If a subsequent re-screen is required for a cohort after the first 
permissible re-screening, the case should be discussed with the Sponsor. Any assessments 
that fall out of the screening window must be repeated. 
In the case where a safety laboratory assessment and/or PFTs at screening is outside of the 
range specified in the eligibility criteria, the assessment may be repeated once prior to the 
first dose of study treatment. If the repeat value remains outside of the specified range, the 
participant must be excluded from the study. If PFTs are to be repeated, only the tests that 
are felt to be questionable should be repeated (i.e., spirometry or DLCO). 
If a participant must be re-screened, for study entry, results from previous screening 
assessments may be used, as long as the screening windows for those assessments are met 
and all spirometry data used for subject qualification are derived from a single day. 
8.1.1 
Eligibility screening 
8.1.1.1 
Hepatitis screen, HIV screen 
All participants will be screened for Hepatitis B surface antigen (HBsAg), Hepatitis B 
surface anti-body (HBsAb), and Hepatitis B core anti-body (HBcAb). Screening for 
Hepatitis C will be based in HCV antibodies and if positive, HCV RNA levels should be 
determined. 
Evaluation for HIV seropositivity will be performed, and, if positive, confirmation by a 
second technique available at the laboratory site e.g. western blot. Appropriate counseling 
will be made available by the investigator in the event of a positive confirmatory test. 
Notification of state and federal authorities, as required by law, will be the responsibility of 
the investigator. 
This will be recorded as source data only by the use of an "S" for the corresponding criteria 
in Table 8-1 (Assessment Schedule) of the protocol. 
8.1.1.2 
Alcohol test, Drug screen, Urine cotinine 
Not applicable 
8.1.2 
Information to be collected on screening failures 
Participants who sign an informed consent form and are subsequently found to be ineligible 
prior to randomization will be considered a screen failure. The reason for screen failure 
should be recorded on the appropriate Case Report Form. The demographic information, 
informed consent, and Inclusion/Exclusion pages must also be completed for screen failure 
participants. No other data will be entered into the clinical database for participants who are 
screen failures, unless the participant experienced a serious adverse event during the 
screening phase (see Section 10.1.3 for reporting details). If the participant fails to be 
randomized, the IRT must be notified within 2 days of the screen fail that the participant 
was not randomized. 

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Participants who are randomized and fail to start treatment, e.g. participants randomized in 
error, will be considered early terminators. The reason for early termination should be 
recorded on the appropriate Case Report Form. 
8.2 
Participant demographics/other baseline characteristics 
Country-specific regulations should be considered for the collection of demographic and 
baseline characteristics in alignment with the CRF. 
Participant demographics: year of birth or age, sex, race/predominant ethnicity (if 
permitted), smoking history, and relevant medical history/current medical conditions (until 
date of signature of informed consent) will be recorded in the eCRF. Where possible, the 
diagnosis and not symptoms should be recorded. Participant race/ethnicity data are collected 
and analyzed to identify any differences in the safety and/or efficacy profile of the treatment 
due to these characteristics. In addition, the diversity of the study population will be assessed 
as required by Health Authorities. 
All prescription medications, over-the-counter drugs, and significant non-drug therapies 
prior to the start of the study must be documented. See the protocol Section 6.2.1 
Concomitant Therapy for further details on what information must be recorded on the 
appropriate page of the eCRF. 
8.3 
Efficacy 
Pharmacodynamic samples will be collected at the timepoints defined in the Cohort Specific 
Assessment Schedule (Section 17). Follow instructions outlined in the Laboratory manual 
regarding sample collection, numbering, processing, and shipment. 
Pharmacodynamic (PD) samples will be obtained and evaluated in all participants at all dose 
levels, including the placebo group. 
8.3.1 
Appropriateness of efficacy assessments 
• The 6MWT is a well standardized and simple test to assess physical performance 
• DLCO is a pulmonary function test that assesses the diffusion of gas in the lungs 
• HRCT is a method of radiographic examination which is more precise than chest x-ray 
for the diagnosis and monitoring of fibrotic diseases in the lung 
• Spirometry is a component of pulmonary function testing that assesses volume of 
airflow movement  
8.3.2 
6-Minute Walk Test 
A standardized Six-Minute Walk Test (6MWT) will be performed considering guidance for 
the test procedures described by ERS and ATS guidelines (Holland et al 2014). 
The six-minute walk will be carried out by a trained technician. 
The 6MWT must be performed after all ECGs, PFTs and PROs have been completed. 
Two walks will be conducted for each 6MWT and both scores will be recorded. 
The participant should rest for at least 30 minutes between walks and may use this time to 
perform other protocol activities. 
Please refer to vendor training for additional details. 

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8.3.3 
Diffusing Capacity (DLCO) 
Diffusion capacity for carbon monoxide (DLCO) will be determined according to ATS 
guidelines (Graham et al 2017). DLCO should be adjusted for hemoglobin, using the 
hemoglobin value collected at the same visit. 
Please refer to vendor manual for details. 
8.3.4 
High Resolution CT of Chest 
High Resolution Computed Tomography (HRCT) will be performed at screening (which 
will be used as the baseline measure) and at Week 26. At the time points specified in the 
schedule, an HRCT scan of the lung, without contrast agent, will be acquired. 
The acquisition will include inspiratory and expiratory image sets at both assessment time 
points. In all participants within the study, the baseline and follow-up HRCT scan should be 
performed where possible on the same scanner. Protocol specific requirements of the HRCT 
and machine settings are provided to all sites as part of a separate Imaging Manual. 
Additionally, the imaging vendor will provide centralized review of the HRCT scans. 
The methods for assessment and recording are specified in the Imaging Review Charter. 
In summary, evaluation of the HRCT scans may be used to assess extent of: 
• Lung parenchymal classification analysis and valuation of change from baseline 
compared to week 26 of HRCT  
• Percent of lung or regional volume which constitutes normal lung tissue, areas of 
low attenuation (LAA), ground-glass opacity, reticulation, honey-combing, and 
composites of these indices. 
HRCT involves exposure to radiation. The total amount of radiation for acquisition at 
baseline and Week 26 of HRCT scans will be optimized to be within the annual limits of 
exposure defined in both EU and NA guidelines. The total radiation received in this study 
is equivalent to approximately 3-5 years of normal radiation received in everyday life. 
This amount of radiation is considered to be a minor to intermediate risk and is necessary to 
obtain the research information desired. 
Note: The coded medical images will be used primarily for analysis as described in this 
protocol; however, the images may also be used for the development and evaluation of new 
analysis methods directly related to the area of research that this study covers. 
8.3.5 
Spirometry 
Spirometry testing will be performed according to the American Thoracic Society guidelines 
(Graham et al 2019) at screening to assess participant’s eligibility for the study and as 
detailed in the assessment schedule. 
Please refer to vendor manual for details. 
8.4 
Safety 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed. 
For details on AE collection and reporting, refer to Section 10.1. 
As per Section 4.6, during a Public Health Emergency as declared by Local or Regional 
authorities (i.e. pandemic, epidemic or natural disaster), that limits or prevents on-site study 

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visits, regular phone or virtual calls can occur (every 4 weeks or more frequently if needed) 
for safety monitoring and discussion of the participant´s health status until it is safe for the 
participant to visit the site again. 
Table 8-2 
Safety Assessments 
Assessment 
Specification 
Physical Examination 
A complete physical examination will include the examination of 
general appearance, skin, neck (including thyroid), eyes, ears, nose, 
throat, lungs, heart, abdomen, back, lymph nodes, extremities, 
vascular, and neurological. If indicated based on medical history 
and/or symptoms, rectal, external genitalia, breast, and pelvic 
exams will be performed. 
A limited physical exam that includes the examination of general 
appearance, vital signs (blood pressure [SBP and DBP] and pulse), 
and Cardiac and Pulmonary exams must be performed. Symptom 
driven for all other organ systems. A limited physical exam will be at 
all visits starting from day 29 except where a complete physical 
examination is required (see above). 
Information for all physical examinations must be included in the 
source documentation at the study site. Clinically relevant findings 
that are present prior to signing informed consent must be recorded 
on the appropriate CRF that captures medical history. Significant 
findings made after signing informed consent that meet the definition 
of an Adverse Event must be recorded as an adverse event. 
Vital Signs 
Vital signs will include the collection of body temperature (recorded 
in °C), blood pressure (BP) and pulse measurements. 
After the participant has been sitting for 3 minutes, with back 
supported and both feet placed on the floor, systolic and diastolic 
BP will be measured. 
Height and weight 
Height in centimeters (cm) and body weight (to the nearest 
0.1 kilogram (kg) in indoor clothing, but without shoes) will be 
measured as specified in Table 8-1. 
Body mass index (BMI) will be calculated using the following 
formula: 
• 
BMI = Body weight (kg) / [Height (m)]2 
The screening visit height measurement will be used for BMI 
calculations throughout the study. 
8.4.1 
Laboratory evaluations 
If participants cannot visit the site for safety lab assessments conducted through central labs, 
local lab collection may be used during a Public Health Emergency as declared by Local or 
Regional authorities (i.e. pandemic, epidemic, or natural disaster), that limits or prevents 
on-site study visits. 
Clinically significant abnormalities must be recorded as either medical history/current 
medical conditions or adverse events as appropriate. 
In the case where a laboratory range is not specified by the protocol, but a value is outside 
the reference range for the laboratory at screening, a decision regarding whether the result 
is of clinical significance or not shall be made by the investigator and shall be based, in part, 
upon the nature and degree of the observed abnormality. 

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In all cases, the investigator must document in the source documents the clinical 
considerations (i.e., result was/was not clinically significant and/or medically relevant). 
A central laboratory will be used for analysis of all safety specimens collected. Details on 
the collection, shipment of samples and reporting of results by the central laboratory are 
provided to investigators in the central laboratory manual. 
Urinalysis 
A midstream urine sample (approx. 30 mL) will be obtained, in order to avoid contamination 
with epithelial cells and sediments and allow proper assessments. 
Special clinical laboratory evaluations 
All abnormal lab results must be evaluated for criteria defining an adverse event and 
reported as such if the criteria are met. For those lab adverse events, repeated evaluations 
are mandatory until normalization of the result(s) or until the result is no longer considered 
to be clinically significant. 
Table 8-3 
Laboratory Evaluations 
Test Category 
Test Name 
Hematology 
Hematocrit, Hemoglobin, Ert. Mean Corpuscular Hemoglobin, Ery. Mean 
Corpuscular HGB Concentration, Ery. Mean Corpuscular 
Volume, Platelets, Erythrocytes, Leukocytes, Erythrocyte Cell Morphology, 
Differential (Basophils, Eosinophils, Lymphocytes, Monocytes, 
Neutrophils, Bands, Other (absolute value and %s) 
Chemistry 
Albumin, Alkaline phosphatase, ALT, AST, Gamma-glutamyl-transferase 
(GGT), Lactate dehydrogenase (LDH), Bicarbonate, Calcium, Magnesium, 
Phosphate, Chloride, Sodium, Potassium, Creatinine, Creatine 
kinase, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Total Cholesterol, 
LDL Cholesterol, HDL Cholesterol, Total Protein, Triglycerides, Urea 
Nitrogen or Urea, Uric Acid, Amylase, Lipase, Glucose (non-fasting) 
Urinalysis 
Microscopic Panel (Erythrocytes, Leukocytes, Casts, Crystals, Bacteria, 
Epithelial cells) 
Macroscopic Panel (Dipstick) (Color, Bilirubin, Blood, Macroscopic Blood, 
Glucose, Ketones, Leukocytes esterase, Nitrite, pH, Protein, Specific 
Gravity, Urobilinogen 
Coagulation 
Prothrombin (PT), International normalized ratio INR), Activated partial 
thromboplastin time (APTT) 
Hepatitis markers 
Hepatitis B Virus DNA, Hepatitis B surface antigen (HBsAg), Hepatitis B 
surface anti-body (HBsAb), Hepatitis B core anti-body (HBcAb), Hepatitis 
C Virus RNA 
Hepatic and renal 
follow-up 
PT/INR urine PCR and albumin-creatinine ratios (refer to Section 16.1 and 
Section 16.2, hepatic and renal event follow-up to ensure recommended 
tests are listed) 
These tests are in addition to routine testing, to be performed only in 
follow-up to safety events when indicated in Section 16.1 and 
Section 16.2, hepatic and renal event follow-up 
Additional tests 
See Section 17 if applicable 
Pregnancy Test 
Serum / Urine pregnancy test (refer to Section 8.4.3) 

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8.4.2 
Electrocardiogram (ECG) 
Electrocardiograms (ECGs) must be recorded after 10 minutes rest in the seated or supine 
position to ensure a stable baseline. The preferred sequence of cardiovascular data collection 
during study visits is ECG collection first, followed by vital signs, blood sampling, and any 
remaining assessments for that visit (refer to flow diagram below). 
Figure 8-1 
Timing of study procedures 
 
The Fridericia QT correction formula (QTcF) must be used for clinical decisions. 
The investigator must calculate QTcF if it is not auto calculated by the ECG machine. 
Single local 12 lead ECGs are collected. 
ECGs will be locally collected and evaluated. Interpretation of the tracing must be made by 
a qualified physician and documented on the appropriate CRF. Each ECG tracing should be 
labeled with the study number, participant initials (where regulations permit), participant 
number, date, and kept in the source documents at the study site. Clinically significant 
abnormalities present at screening should be reported on the appropriate CRF. 
Clinically significant findings must be discussed with Novartis prior to enrolling the 
participant in the study. New or worsened clinically significant findings occurring after 
informed consent must be recorded as adverse events. 
The original ECGs on non-heat sensitive paper, appropriately signed, must be archived at 
the study site. 
Additional, unscheduled, safety ECGs may be repeated at the discretion of the investigator 
at any time during the study as clinically indicated. For any ECGs with participant safety 
concerns, two additional ECGs must be performed to confirm the safety finding. ECGs will 
be reviewed locally for clinically significant ECG findings at baseline before administration 
of study treatment and during the study. 
Clinically significant abnormalities must be recorded on the CRF as either medical 
history/current medical conditions or adverse events as appropriate. 
8.4.3 
Pregnancy and assessments of fertility 
A condom is required for all sexually active male participants to prevent them from fathering 
a child AND to prevent delivery of study treatment via seminal fluid to their partner. 
In addition, male participants should not donate sperm for the time period specified in  
Section 17. 
All pre-menopausal women who are not surgically sterile will have pregnancy testing. 
Additional pregnancy testing might be performed if requested by local requirements. 
If participants cannot visit the site to have serum pregnancy tests during a Public Health 
emergency as declared by Local or Regional authorities, i.e. pandemic epidemic, or natural 

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disaster, that limits or prevents on-site study visits, urine pregnancy test kits may be used. 
Relevant participants can perform the urine pregnancy test at home and report the result to 
the site. It is important that participants are instructed to perform the urine pregnancy test 
first and only if the test result is negative proceed with the administration of the study 
treatment. A communication process should be established with the participant so that the 
Site is informed and can verify the pregnancy test results (e.g. following country specific 
measures). 
Assessments of fertility 
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained 
as source documents. Subsequent hormone level assessment to confirm the woman is not of 
child-bearing potential must also be available as source documentation in the following 
cases: 
1. Surgical bilateral oophorectomy without a hysterectomy 
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile. 
In the absence of the above medical documentation, FSH testing is required of any female 
participant regardless of reported reproductive/menopausal status at screening/baseline. 
8.4.4 
Appropriateness of safety measurements 
Pulmonary function and status are monitored by assessments, including spirometry, DLCO, 
 6MWT, and PROs amongst others, which are detailed under the efficacy measures in 
the study. Cohort specific safety assessments are detailed in Section 17. 
Further safety assessments (e.g. hematology, serum chemistry, coagulation, ECGs, vital 
signs, physical exams) are standard for investigations monitoring general safety in phase 2 
clinical trials. 
8.5 
Additional assessments 
8.5.1 
Clinical Outcome Assessments (COAs) 
As per Section 4.6, during a Public Health Emergency as declared by Local or Regional 
authorities (i.e. pandemic, epidemic, or natural disaster), that limits or prevents on-site study 
visits, COA data may be collected remotely. 
Patient reported outcomes (PRO) 
The participant must be given the PRO measure(s) to be completed at the scheduled visit 
before 6MWT. Participant's refusal to complete all or any part of a PRO measure should be 
documented in the study data capture system and should be captured as a protocol deviation. 
Handling of protocol deviations can be modified if needed per study protocol. 
Participant questionnaires should be completed in the language most familiar to the 
participant. 
If self-administered: 
The participant should be given sufficient space and time to complete the PRO measure(s). 
The site personnel should check PRO measure(s) for completeness and ask the participant 
to complete any missing responses. 
CCI

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8.5.1.1 
Leicester Cough Questionnaire 
The Leicester Cough Questionnaire (LCQ) is a 19-item chronic cough/respiratory-specific 
measure designed to assess the impact of chronic cough on health-related quality of life 
(HRQoL), using a recall period of the last 24 hours. It can be completed in less than 
5 minutes. 
8.5.1.2 
Living with IPF (Impacts and Symptoms Modules) 
Living with IPF (L-IPF) is a tool that assesses symptoms and impacts of IPF. The Symptoms 
Module consists of 20 questions. This module is designed to assess symptoms experienced 
from IPF over the last 24 hours. The symptoms questions are in relation to physical 
activities, cough, and energy level. The last 5 questions are regarding supplemental oxygen 
use. The Impacts Module consists of 20 questions on how IPF affects quality of life over the 
last 7 days. 
8.5.1.3 
K-BILD 
The King’s Brief Interstitial Lung Disease (K-BILD) is a 15-item HRQOL questionnaire. 
The K-BILD questionnaire assesses 3 domains (breathlessness/activities, psychological and 
chest symptoms) with a 2-week recall. 
8.5.1.4 
Raghu Scale for Pulmonary Fibrosis 
The Raghu-Scale for Pulmonary Fibrosis (R-Scale for PF) is a questionnaire designed to 
assess the impact of lung disease on quality of life. R-Scale for PF consists of 5 questions 
with a 2-week recall. 
8.5.2 
Pharmacokinetics 
PK samples will be collected at the visits defined in Section 17. 
8.5.3 
Biomarkers 
The biomarkers selected in this study may explore the potential mechanism of action, 
pharmacodynamics, and safety responses to the drug treatment. The biomarker strategy may 
enhance our understanding of the mechanism of the compound on inflammation and fibrosis 
in humans with IPF disease. The pharmacogenetic assessment will be performed to examine 
the association of genetic variances related to drug response and metabolism. The timing 
and details of the samples collected are defined in the PK/PD and Biomarker Assessment 
Schedule in Section 17. Serum and plasma biomarkers will be collected, stored, and banked 
for future testing. 
Exploratory Biomarkers 
Serum and plasma samples will be collected for exploratory disease related biomarker 
analysis. Additional samples for biomarkers will be collected, banked, and stored. 
Protein profiling of blood samples may be analyzed in multiplex, hypothesis-free platforms 
to study protein biomarkers. 
Samples will be collected at the time points defined in the PK/PD and Biomarker 
Assessment Schedule (Section 17). The list may be changed or expanded further, as it is 
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the study. Follow instructions for sample collection, numbering, processing, and shipment 
provided in the laboratory manual. 
Descriptions of the assays, platforms, and technologies to be used in the exploratory 
biomarker evaluations will be included in the associated bioanalytical data reports. Clinical 
samples for the assessment of exploratory biomarkers may be stored and their processing 
and analysis conditioned to the decisions to be made based on overall study outcome and/or 
future scientific needs. Exploratory biomarker samples remaining after analyses may be 
stored for up to 15 years to address additional relevant scientific questions. 
To assess the impact of the drug on disease related biomarkers; markers may include but not 
limited to: 
 
 
 
 
 
 
Samples will be the collected at the time point defined in the Assessment schedule 
(Section 17). 
Detailed instructions for sample collection, numbering, processing, and shipment will be 
provided in the Central Lab Manual.  
DNA sampling / Pharmacogenetics 
Exploratory DNA Sampling (Optional) 
The study includes an optional genetic research component which requires a separate 
informed consent signature if the participant agrees to participate. As permitted by local 
governing regulations and by IRB/EC, it is required as part of this protocol that the 
investigator presents these options to the participant. 
The purpose of genetic research may be to better understand the safety and efficacy of 
treatment, or to learn more about human diseases, or to help develop ways to detect, monitor 
and treat diseases. 
As technology changes over time, the most appropriate technology will be used at the time 
the exploratory genetic research is performed. This may include the study of the entire 
genome. 
Sample(s) will be collected at the time point(s) defined in the PK/PD and Biomarker 
Assessment Schedule (Section 17). 
Laboratory manuals will be provided with detailed information on sample collection, 
handling, and shipment. 
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DNA samples 
The use of DNA to search for biomarkers of disease and drug action is exploratory. 
Any results from this DNA study will not be placed in the participant’s medical records. 
To maximize confidentiality, all samples will be double coded to prevent the exposure of 
the participant’s information and identity. This double-coding process allows Novartis to go 
back and destroy the sample at the participant’s request. In addition, sample information is 
stored in one secured database while genetic data is stored in an independent secured 
database. 
8.5.3.1 
 
 
  
 
 
 
 
 
 
 
 
8.5.3.2 
Use of residual biological samples 
Residual blood, serum, and plasma samples may be used for another protocol specified 
endpoint. Any residual samples remaining after the protocol-defined analyses have been 
performed may be used for additional exploratory analyses. This may include but is not 
limited to using residual samples for protein binding, metabolite profiling or quantification, 
biomarkers of transporters or metabolic enzyme activity or other bioanalytical purposes (e.g. 
cross check between different sites and/or stability assessment). The results from these 
exploratory analyses may not necessarily be included in the clinical study report. 
8.5.4 
Immunogenicity 
Immunogenicity samples may be obtained in cohorts where the IP is thought to have the 
potential to elicit an immunogenic reaction, including the placebo groups in those cohorts. 
In case of suspected allergic hypersensitivity, the participant should return to the site and a 
sample to assess immunogenicity will be collected. 
In case of positive immunogenicity, backup of previous pre-dose PK samples could be used 
to better characterize the onset of immunogenicity response. 
Follow instructions outlined in the laboratory manual regarding sample collection, 
numbering, processing, and shipment. 
Please refer to Section 17. 
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Immunogenicity analytical method(s) 
A validated ligand binding assay (i.e. ELISA, MSD, etc.) will be used for the detection of 
potential antibodies per Section 17. Confirmed immunogenicity positive samples will be 
further analyzed for presence of neutralizing antibodies using a validated method. 
The detailed methods for immunogenicity assessment will be described in the Bioanalytical 
Data Report. 
9 
Discontinuation and completion 
9.1 
Discontinuation from study treatment and from study 
9.1.1 
Discontinuation from study treatment 
Discontinuation of study treatment for a participant occurs when study treatment is 
permanently stopped for any reason (prior to the planned completion of study drug 
administration) and can be initiated by either the participant or the investigator. 
The investigator must discontinue study treatment for a given participant if he/she believes 
that continuation would negatively impact the participant's well-being. 
Participants who discontinue study treatment must return for an Early End of Treatment visit 
as soon as possible, but within 4 weeks after discontinuation of treatment. All assessments 
planned for the Day 183 visit will be performed. HRCT will only be done if discontinuation 
occurs after Day 85. If the End of Treatment visit occurs in the visit window for the next 
scheduled visit, then the scheduled visit may serve as the Early End of Treatment visit, and 
all assessments for the End of Treatment visit should occur at that time. Participants will go 
on to complete all remaining visits as scheduled, including the Day 183 visit and Safety 
Follow-up visit (see Table 8-1 for a list of assessments to occur at the End of Treatment and 
Safety Follow-Up visits). For participants who continue scheduled visits, the HRCT scan 
will be performed as scheduled at the Day 183 visit. 
Discontinuation from study treatment is required under the following circumstances: 
• Participant/guardian decision 
• The participant becomes pregnant. Study treatment must be discontinued immediately. 
Report the pregnancy according to instructions in Section 10.1.4 
• If organ transplantation becomes necessary during the study treatment 
• The participant is unwilling or unable to comply with the protocol 
• Adverse event that puts the participant at risk if continuation on investigational product 
or in the study, at the discretion of the investigator. 
• If a liver or renal event occurs, follow guidelines outlines in Section 16.1 (Appendix 1) 
and Section 16.2 (Appendix 2), respectively, regarding discontinuation of study 
treatment. 
If discontinuation from study treatment occurs, the investigator should make a reasonable 
effort to understand the primary reason for the participant’s discontinuation from study 
treatment and record this information. 

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After discontinuation from study treatment, at a minimum the following data should be 
collected at clinic visits or via telephone/email contact: 
• New / concomitant treatments 
• Adverse Events / Serious Adverse Events 
The investigator must also contact the IRT to register the participant’s discontinuation from 
study treatment. 
9.1.2 
Discontinuation from study 
Discontinuation from study is when the participant permanently stops receiving the study 
treatment, and further protocol-required assessments or follow-up, for any reason. 
If a participant is discontinued from the study, an Early End of Treatment visit will be 
scheduled or performed as soon as possible but within 4 weeks. All assessments planned for 
the Day 183 visit will be performed except HRCT. If early EOT falls on or after Day 85 
visit, HRCT should also be performed (see Table 8-1 for a list of assessments to occur at the 
End of Treatment visit). 
If a participant is unwilling or unable to attend, at the minimum, the End of Treatment visit, 
and decides to withdraw from the study, the reason for withdrawal will be documented and 
no further assessments will be obtained. 
Please note, if a participant decides to discontinue from the study, a withdrawal of consent 
should NOT be completed unless the participant meets the particular criteria noted in 
Section 9.2. 
9.1.3 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits without 
stating an intention to discontinue from study treatment or discontinue from study or 
withdraw consent/oppose to the use of their data/biological samples, the investigator must 
show "due diligence" by documenting in the source documents steps taken to contact the 
participant, e.g. dates of telephone calls, registered letters, etc. A participant should not be 
considered as lost to follow-up until this "due diligence" has been completed. 
9.2 
Withdrawal of informed consent/Opposition to use 
data/biological samples 
Withdrawal of consent/opposition to use of data and/or biological samples occurs in 
countries where the legal justification to collect and process the data is consent and when a 
participant meets ALL three criteria: 
• Explicitly requests to stop use of their data  
and 
• No longer wishes to receive study treatment 
and 
• Does not want any further visits or assessments (including further study-related 
contacts) 
This request should be as per local regulations (e.g. writing) and recorded in the source 
documentation. 

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Withdrawal of consent impacts ability to further contact the participant, collect follow-up 
data (e.g. to respond to data queries) and potentially other country-specific restrictions. It is 
therefore very important to ensure accurate recording of withdrawal vs. discontinuation 
based on the protocol definitions of these terms. 
In this situation, the Investigator should make a reasonable effort (e.g. telephone, e-mail, 
letter) to understand the primary reason for the participant’s decision to withdraw their 
consent/exercise data privacy rights and record this information. The Investigator shall 
clearly document if the participant has withdrawn his/her consent for the use of data in 
addition to a study discontinuation. 
Study treatment must be discontinued, and no further assessments conducted, and the data 
that would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 
If the participant agrees, an End of Treatment visit will be scheduled or performed prior to 
the participant’s withdrawal of consent/exercise data privacy rights. All assessments 
planned for the Day 183 visit will be performed except HRCT. If early EOT falls on or after 
Day 85 visit, HRCT should also be performed (see Table 8-1 for a list of assessments to 
occur at the End of Treatment visit). 
Further details on withdrawal of consent or the exercise of participants' data privacy rights 
are included in the corresponding informed consent form. 
Novartis will continue to retain and use all research results (data) that have already been 
collected for the study evaluation, including processing of biological samples that has 
already started at time of consent withdrawal/opposition. No new Personal Data (including 
biological samples) will be collected following withdrawal of consent/opposition. 
9.3 
Study stopping rules 
The Sponsor may terminate this study, or a cohort, at any time. The Sponsor will notify 
investigators if the study is to be placed on hold, completed, or terminated. 
Cohort stopping rules 
Enrollment in a cohort will be placed on hold if: 
• The Sponsor considers that the number and/or severity of AEs, abnormal safety 
monitoring tests, or abnormal laboratory findings justify putting the cohort on hold 
Additionally, the DMC will conduct regular reviews of all safety data in an unblinded 
format. Following each review, the DMC will provide a recommendation to the Sponsor 
regarding the appropriateness of continuing the cohort from a safety perspective, as well as 
any other recommendations relevant to study conduct and/or participant safety. 
The DMC may recommend discontinuing the cohort if the event rate in the investigational 
treated arm is 20% higher compared with placebo. The events include, but may not be 
limited to: 
• cumulative number of deaths and/or; 
• number of lung transplantations and/or; 
• cumulative number of participants with a confirmed absolute decline of % predicted 
FVC ≥15 from baseline. 

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The meeting intervals and procedures used to provide and assess the data will be described 
in detail in the DMC Charter. 
9.4 
Study completion and post-study treatment 
Study completion is defined as when the last participant finishes their End of Study visit and 
any repeat assessments associated with this visit have been documented and followed-up 
appropriately by the investigator. 
All randomized and/or treated participants will have a safety follow-up visit at least 30 days 
(see Section 17) after the last administration of study treatment. The information collected 
is kept as source documentation. All SAEs reported during this time period must be reported 
as described in Section 10.1.3. 
Continuing care should be provided by the investigator and/or referring physician based on 
participant availability for follow-up. This care may include: 
• Enrollment into another Cohort, if eligible and applicable 
9.5 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time. 
Reasons for early study or cohort termination may include but are not limited to: 
• Unexpected, significant, or unacceptable safety risk to participants enrolled in the 
study 
• Decision based on recommendations from applicable board(s) after review of safety 
and efficacy data 
• Discontinuation of study drug development 
In taking the decision to terminate, Novartis will always consider participant welfare and 
safety. Should early termination be necessary, participants must be seen as soon as possible 
for an EOT visit and enter into the safety follow-up period as per their respective cohort. 
The investigator may be informed of additional procedures to be followed in order to ensure 
that adequate consideration is given to the protection of the participant’s interests. 
The investigator or sponsor depending on local regulation will be responsible for informing 
IRBs/IECs of the early termination of the trial. 
10 
Safety monitoring, reporting and committees 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical 
investigation participant after providing written informed consent for participation in the 
study. Therefore, an AE may or may not be temporally or causally associated with the use 
of a medicinal (investigational) product. 
The investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events. 

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Novartis qualified medical personnel will be readily available to advise on trial related 
medical questions or problems. 
The occurrence of adverse events must be sought by non-directive questioning of the 
participant at each visit during the study. Adverse events also may be detected when they 
are volunteered by the participant during or between visits or through physical examination 
findings, laboratory test findings, or other assessments. 
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with 
them, accompanied by the following information (as far as possible) (if the event is serious 
refer to Section 10.1.2): 
1. The severity grades  
• mild: usually transient in nature and generally not interfering with normal 
activities 
• moderate: sufficiently discomforting to interfere with normal activities 
• severe: prevents normal activities 
2. The investigator is obligated to assess the relationship between any treatment used in 
the study (study treatment) and each occurrence of each AE.  The investigator will use 
clinical judgement to determine the relationship. A reasonable possibility of a 
relationship conveys that there are facts, evidence, and/or arguments to suggest a 
causal relationship, rather than a relationship cannot be ruled out. Alternative causes, 
such as underlying disease(s), concomitant therapy, and other risk factors, as well as 
the temporal relationship of the event to study intervention administration, will be 
considered and investigated. For causality assessment, the investigator will also 
consult the IB and/or product information, for marketed products. 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
3. Its duration (start and end dates or ongoing) and the outcome must be reported 
4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken regarding with study treatment. 
All adverse events must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed 
• Dose Reduced/increased 
• Drug interrupted/permanently discontinued 
6. Its outcome  
Conditions that were already present at the time of informed consent should be recorded in 
medical history of the participant. 
Adverse events (including lab abnormalities that constitute AEs) should be described using 
a diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 30 days (or 5 half-lives, 
whichever is longer) following the last dose of study treatment. Details for Safety Follow-
up are outlined for each cohort in Section 17. 
Once an adverse event is detected, it must be followed until its resolution or until it is judged 
to be permanent (e.g. continuing at the end of the study), and assessment must be made at 

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each visit (or more frequently, if necessary) of any changes in severity, the suspected 
relationship to the interventions required to treat it, and the outcome. 
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator's Brochure (IB). 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at 
least one of the following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through 
a review of values outside of normal ranges/clinically notable ranges, significant changes 
from baseline or the previous visit, or values which are considered to be non-typical in 
participant with the underlying disease. 
10.1.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the 
following criteria: 
• fatal 
• life-threatening 
Life-threatening in the context of a SAE refers to a reaction in which the participant was at 
risk of death at the time of the reaction; it does not refer to a reaction that hypothetically 
might have caused death if it were more severe (please refer to the ICH-E2D Guidelines). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect, fetal death or a congenital abnormality 
or birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since signing the informed 
consent 
• social reasons and respite care in the absence of any deterioration in the 
participant’s general condition 
• treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g. defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
participant or might require intervention to prevent one of the other outcomes listed above. 
Such events should be considered as “medically significant.” Examples of such events are 

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intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias, or convulsions that do not result in hospitalization or development of 
dependency or abuse (please refer to the ICH-E2D Guidelines). 
All new malignant neoplasms will be assessed as serious under “medically significant” if 
other seriousness criteria are not met and the malignant neoplasm is not a disease 
progression of the study indication. 
All reports of intentional misuse and abuse of the product are also considered serious adverse 
events irrespective of whether a clinical event has occurred. 
Any suspected transmission via a medicinal product of an infectious agent is also considered 
a serious adverse reaction. 
10.1.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the 
participant has provided informed consent and until the last study visit must be reported to 
Novartis safety immediately, without undue delay, but under no circumstances later than 
within 24 hours of obtaining knowledge of the events (Note: If more stringent, local 
regulations regarding reporting timelines prevail). Detailed instructions regarding the 
submission process and requirements are to be found in the Investigator folder provided to 
each site. Information about all SAEs is collected and recorded on the Serious Adverse 
Event Report Form; all applicable sections of the form must be completed in order to provide 
a clinically thorough report. 
1. SAEs occurring after the participant has provided informed consent until the time the 
participant is deemed a Screen Failure must be reported to Novartis. 
2. Randomized and Treated Participants: SAEs collected between time participant signs 
ICF until EOS safety follow-up visit. 
All follow-up information for the SAE including information on complications, progression 
of the initial SAE and recurrent episodes must be reported as follow-up to the original 
episode immediately, without undue delay, but under no circumstances later than within 
24 hours of the investigator receiving the follow-up information (Note: If more stringent, 
local regulations regarding reporting timelines prevail). An SAE occurring at a different 
time interval or otherwise considered completely unrelated to a previously reported one 
must be reported separately as a new event. 
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert 
(new occurrence) and is thought to be related to the study treatment, a CMO & PS 
Department associate may urgently require further information from the Investigator for 
health authority reporting. Novartis may need to issue an Investigator Notification (IN) to 
inform all Investigators involved in any study with the same study treatment that this SAE 
has been reported. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported 
to the competent authorities and relevant ethics committees in accordance with EU 
Guidance 2011/C 172/01 or EU Clinical Trial Regulation 536/2014 as per national 
regulatory requirements in participating countries. 
Subjects will be followed for all SAEs until their last study visit. Thereafter, the event should 
be reported to Novartis Safety only if the investigator considers the SAE to be related to 
study treatment, unless otherwise specified by local laws/ regulations. 

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SAEs that are ongoing when the subject completes or discontinues the study will be followed 
by the investigator until the event has resolved, stabilized, or returned to baseline status. 
SAE outcome will be recorded on the CRF, as applicable. Only SAEs that are unresolved 
will continue to be followed by the investigator. 
10.1.3.1 Prescheduled or Elective Procedures or Routinely Scheduled 
Treatments 
A prescheduled or elective procedure or a routinely scheduled preventative health procedure 
(e.g. colonoscopy) will not be considered an SAE, even if the subject is hospitalized. 
The study site must document all of the following: 
• The prescheduled or elective procedure or routinely scheduled treatment was 
scheduled (or was on a waiting list to be scheduled) prior to obtaining the subject’s 
consent to participate in the study. 
• The condition requiring the prescheduled or elective procedure or routinely scheduled 
treatment was present before and did not worsen or progress in the opinion of the 
investigator between the subject’s consent to participate in the study and the time of 
the procedure or treatment. 
• The prescheduled or elective procedure or routinely scheduled treatment is the sole 
reason for the intervention or hospital admission. 
If a subject is hospitalized due to local requirements for administration of the study 
treatment, the hospitalization should not be considered an SAE unless one of the 
requirements in Section 10.1.2 is met. 
10.1.4 
Pregnancy reporting 
Pregnancies 
If a female trial participant becomes pregnant, the study treatment should be stopped, and 
the pregnancy consent form should be presented to the trial participant. The participant must 
be given adequate time to read, review and sign the pregnancy consent form. This consent 
form is necessary to allow the investigator to collect and report information regarding the 
pregnancy. To ensure participant safety, each pregnancy occurring after signing the 
informed consent must be reported to Novartis within 24 hours of learning of its occurrence. 
The pregnancy should be followed up to determine outcome, including spontaneous or 
voluntary termination, details of the birth, and the presence or absence of any birth defects, 
congenital abnormalities, or maternal and/or newborn complications. 
Pregnancy should be recorded and reported by the investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to the investigational 
product any pregnancy outcome. Any SAE experienced during pregnancy must be reported. 
If a female partner of a male trial participant who took study treatment in this study becomes 
pregnant, pregnancy outcomes should be collected. Consent to report information regarding 
these pregnancy outcomes should be obtained from the mother. 
After consent is provided, the pregnancy reporting will occur up to one year after the 
estimated date of delivery. 

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10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant, 
or consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately 
used not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded 
on the appropriate CRF irrespective of whether or not associated with an AE/SAE and 
reported to Safety only if associated with an SAE. Misuse or abuse will be collected and 
reported in the safety database irrespective of it being associated with an AE/SAE within 
24 hours of investigator’s awareness. 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in Dosing 
CRF (Yes/No) 
Document in AE 
eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated 
with an AE 
Only if associated 
with an SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not 
associated with a 
SAE 
For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
10.2 
Additional Safety Monitoring 
10.2.1 
Liver safety monitoring 
To ensure participant safety and enhance reliability in determining the hepatotoxic potential 
of an investigational drug, a standardized process for identification, monitoring and 
evaluation of liver events has to be followed. 
Please refer to Table 16-1 in Appendix 2 for complete definitions of liver laboratory triggers. 
Once a participant is exposed to study treatment, every liver event defined in Table 16-2 
should be followed up by the investigator or designated personnel at the trial site, as 
summarized below. Additional details on actions required in case of liver events are outlined 
in Table 16-3. Repeat liver chemistry tests (i.e. ALT, AST, TBL, PT/INR, ALP and G-GT) 
to confirm elevation. 
• These liver chemistry repeats will be performed using the central laboratory. If results 
will not be available from the central laboratory, then the repeats can also be 
performed at a local laboratory to monitor the safety of the participant. If a liver event 
is subsequently reported, any local liver chemistry tests previously conducted that are 
associated with this event should have results recorded on the appropriate CRF. 
• If the initial elevation is confirmed, close observation of the participant will be 
initiated, including consideration of treatment interruption if deemed appropriate. 
• Discontinuation of the investigational drug (refer to Section 9.1.1), if appropriate 

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• Hospitalization of the participant if appropriate 
• Causality assessment of the liver event 
• Thorough follow-up of the liver event should include 
• These investigations can include based on investigator’s discretion: serology tests, 
imaging, and pathology assessments, hepatologist’s consultancy; obtaining more 
detailed history of symptoms and prior or concurrent diseases, history of 
concomitant drug use, exclusion of underlying liver disease 
• Obtaining a more detailed history of symptoms and prior or concurrent diseases 
• Obtaining a history of concomitant drug use (including nonprescription 
medications and herbal and dietary supplement preparations), alcohol use, 
recreational use, and special diets 
• Imaging such as abdominal US, CT, or MRI, as appropriate 
• Obtaining a history of exposure to environmental chemical agents. 
• Considering gastroenterology or hepatology consultations. 
All follow-up information and procedures performed must be recorded as appropriate in the 
CRF. 
10.2.2 
Renal safety monitoring 
Once a participant is exposed to study treatment, the following two categories of abnormal 
renal laboratory alert values should be assessed during the study period: 
• Serum creatinine increase > 2-fold compared to baseline during normal hydration 
status 
• Any one of the following: 
• Urine protein-creatinine ratio (PCR) ≥1g/g or ≥100 mg/mmol, OR 
• New onset dipstick proteinuria ≥ 3+, OR 
• New onset dipstick hematuria ≥ 3+ (after excluding menstruation, UTI, extreme 
exercise, or trauma) 
Abnormal renal event findings must be confirmed within 48-72 hours after the first 
assessment. 
Once a participant is exposed to study treatment, renal laboratory alerts or renal safety events 
should be monitored and followed up by the investigator or designated trial staff as 
summarized in Table 16-4. 
10.3 
Committees 
10.3.1 
Data Monitoring Committee 
This study will include a data monitoring committee (DMC) which will function 
independently of all other individuals associated with the conduct of this clinical trial, 
including the site investigators participating in the study. The DMC will assess at defined 
intervals the progress of the clinical trial, safety data, and critical efficacy variables and 
recommend to the sponsor whether to continue, modify, or terminate a cohort and/or trial. 
If the sponsor does not follow the recommendations of the DMC to halt or early terminate 
the study, respective health authorities (HAs) and IRBs/IECs will be notified. 

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Specific details regarding composition, responsibilities, data monitoring, and meeting 
frequency, and documentation of DMC reports, minutes, and recommendations will be 
described in a separate charter that is established between the sponsor and the DMC. 
11 
Data Collection and Database management 
11.1 
Data collection 
Data not requiring a separate written record will be defined in the protocol and the 
Assessment Schedule (Table 8-1) and can be recorded directly on the CRFs. All other data 
captured for this study will have an external originating source (either written or electronic) 
with the CRF not being considered as source. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF). The eCRFs built using fully validated secure web-enabled 
software that conforms to 21 CFR Part 11 requirements, investigator site staff will not be 
given access to the EDC system until they have been trained. Automatic validation programs 
check for data discrepancies in the eCRFs and allow for modification and/or verification of 
the entered data by the investigator staff. 
The investigator/designee is responsible for assuring that the data (entered into eCRF) is 
complete, accurate, and that entry and updates are performed in a timely manner. 
The investigator must certify that the data entered are complete and accurate. 
After database lock, the investigator will receive copies of the participant data for archiving 
at the investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
11.2 
Database management and quality control 
Novartis personnel (or designated CRO) will review the data entered by investigational staff 
for completeness and accuracy. Electronic data queries stating the nature of the problem and 
requesting clarification will be created for discrepancies and missing values and sent to the 
investigational site via the EDC system. Designated investigator site staff are required to 
respond promptly to queries and to make any necessary changes to the data. 
Concomitant treatments and prior medications entered into the database will be coded using 
the World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) terminology. 
Dates of screenings, randomizations, screen failures and study completion, as well as 
randomization codes and data about all study treatment (s) dispensed to the participant and 
all dosage changes will be tracked using an Interactive Response Technology (IRT). 
The system will be supplied by a vendor, who will also manage the database. The data will 
be sent electronically to Novartis (or a designated CRO) at specific timelines. 

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Each occurrence of a code break via IRT will be reported to the clinical team and monitor. 
The code break functionality will remain available until study shut down or upon request of 
Novartis. 
Once all the necessary actions have been completed and the database has been declared to 
be complete and accurate, it will be locked, and the treatment codes will be unblinded 
and made available for data analysis/moved to restricted area to be accessed by independent 
programmer and statistician. The database for each cohort may be locked independently of 
the other cohorts. Any changes to the database after that time can only be made after written 
agreement by appropriate Novartis management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (i.e. eCRFs) with the 
investigators and their staff. During the study, Novartis employs several methods of 
ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. The field 
monitor will visit the site to check the completeness of participant records, the accuracy of 
data capture / data entry, the adherence to the protocol and to Good Clinical Practice, the 
progress of enrollment, and to ensure that study treatment is being stored, dispensed, and 
accounted for according to specifications. Key study personnel must be available to assist 
the field monitor during these visits. Continuous remote monitoring of each site’s data may 
be performed by a centralized Novartis/CRA organization. Additionally, a central analytics 
organization may analyze data & identify risks & trends for site operational parameters and 
provide reports to Novartis clinical teams to assist with trial oversight. 
The investigator must maintain source documents for each participant in the study, 
consisting of case and visit notes (hospital or clinic medical records) containing 
demographic and medical information, laboratory data, electrocardiograms, and the results 
of any other tests or assessments. All information on CRFs must be traceable to these source 
documents in the participant's file.  The investigator must also keep the original informed 
consent form signed by the participant (a signed copy is given to the participant). 
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the data capture and/or data entry. Novartis monitoring standards 
require full verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of SAEs, and of data that will be used for all 
primary variables. Additional checks of the consistency of the source data with the CRFs 
are performed according to the study-specific monitoring plan. No information in source 
documents about the identity of the participants will be disclosed. 
12 
Data analysis and statistical methods 
The analysis will be conducted on all subject data available at the time of the analysis. 
Unless otherwise specified, placebo data from each cohort will be pooled. Any data analysis 
carried out independently by the investigator should be submitted to Novartis before 
publication or presentation. 
The main rationale for pooling the placebo data is to reduce the number of participants 
exposed to placebo. The difference between the placebos from different cohorts is expected 
to have little impact on the key efficacy endpoints. 

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12.1 
Analysis sets 
For all analysis sets, participants will be analyzed according to the study treatment(s) 
received. 
The safety analysis set will include all participants who received any study drug. 
The PK analysis set will include all participants with at least one available valid (i.e. not 
flagged for exclusion) PK concentration measurement, who received any study drug and 
with no protocol deviations that impact on PK data. 
The PD analysis set will include all participants with available PD data and no protocol 
deviations with relevant impact on PD data. 
12.2 
Participant demographics and other baseline characteristics 
Demographic and other baseline data including disease characteristics will be summarized 
descriptively by treatment group for the safety set. 
Categorical data will be presented as frequencies and percentages. For continuous data, 
mean, standard deviation, median, minimum, and maximum will be presented. For selected 
parameters, 25th and 75th percentiles will also be presented when applicable. 
Relevant medical histories and current medical conditions at baseline will be summarized 
separately by system organ class and preferred term, by treatment group. 
12.3 
Treatments 
The safety set will be used for the analyses below. Categorical data will be summarized as 
frequencies and percentages. For continuous data, mean, standard deviation, median, 25th 
and 75th percentiles, minimum, and maximum will be presented. 
The duration of exposure in weeks to investigational drug will be summarized by means of 
descriptive statistics using the safety set. 
Concomitant medications and significant non-drug therapies prior to and after the start of 
the study treatment will be summarized according to the Anatomical Therapeutic Chemical 
(ATC) classification system, by treatment group. 
12.4 
Analysis supporting primary objectives 
The primary aim of the study is to assess the efficacy of the investigational products, 
compared to placebo in IPF participants. This will be evaluated by assessing change from 
baseline to end of treatment epoch (26 weeks of treatment) in Forced Vital Capacity (FVC) 
expressed in percent predicted (FVC%p). Reduction of the decrease in change from baseline 
is considered a favorable outcome. 
12.4.1 
Definition of primary endpoint(s) 
The primary endpoint of the study is change from baseline in FVC%p. 
12.4.2 
Statistical model, hypothesis, and method of analysis 
The treatment effect of the primary endpoint will be analyzed using a Bayesian random 
slope model to assess the difference in reduction rate (slope) between the treatment group 
and placebo group. The statistical model will include the intercept, time (as continuous 
variable), the interaction of treatment and time, the interaction of baseline FVC%p and time, 

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and the background therapy  as fixed effect, and the intercept and slope of time for each 
participant as random effects. A robust weakly informative prior for the placebo time slope 
(based on 9 phase II and III studies after 2012 with total of 492 participants) will be used in 
the Bayesian analysis. The robustified informative prior for the change from baseline in 
FVC%p is comprised of 3 components of normal distributed random variables with the 
following information in terms of weight (W), mean (M), and standard deviation (S): 
Table 12-1 
Composition of the robust weakly informative prior for the placebo 
tie slope 
  
Comp1 
Comp2 
Comp3 
W 
0.526 
0.174 
0.300 
M 
-2.93 
-2.75 
-3.00 
S 
0.865 
1.837 
4.754 
By using this prior slope of placebo, a 3% decline at week 26 from the baseline for the 
placebo group is expected. The impact of using this placebo prior means that there would 
be in effect 11 more placebo participants contributing to the data analysis. 
A non-informative prior will be used for the rest of the parameters, assuming the change 
from baseline in FVC%p has a normal distribution with mean=0 and a very large SD (e.g. 
1.E6). The Bayesian posterior mean estimation of the treatment effect over placebo for 
change from baseline FVC %p at the end of treatment (26 weeks) will be derived. Statistical 
evidence of treatment effect will be concluded if the probability that the effect is better than 
placebo by 90% and there is at least 50% probability that the effect over placebo is >1.3%. 
No adjustments for multiplicity will be applied for this exploratory study. 
12.4.3 
Handling of intercurrent events of primary estimand 
Not applicable. 
12.4.4 
Handling of missing values not related to intercurrent event 
Missing data will not be imputed. 
12.4.5 
Sensitivity analyses 
The same Bayesian model stated in Section 12.4.2 will be repeated using non-informative 
prior for the placebo group. The Bayesian posterior probability of the treatment effect 
(treatment - placebo) for the statistical evidence stated in Section 12.4.2 will be derived. 
If a participant who was not on background therapy at randomization initiates treatment with 
background therapy during the study, the subject's data collected after the initiation of 
background therapy will be excluded from the primary analysis. However, a sensitivity 
analysis that includes the excluded data may be performed. 
If a participant discontinues the original background therapy during the treatment period, a 
protocol deviation will be filled and the data generated from the participant will be included 
in the formal analysis. A sensitive analysis may be conducted further by excluding these 
data. 

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12.4.6 
Supplementary analysis 
Frequentist approach of linear mixed model will be conducted to further validate the 
statistical results from main analysis. The model will include all fixed and random effect 
stated in Section 12.4.2. 
A second mixed model will also be fitted with the interaction of the background therapy 
category and the treatment in order to assess the treatment effect within each background 
therapy category. 
Subgroup analyses might be conducted to justify the impact on the robustness of the 
statistical estimate when the situation of participants entering the multiple cohorts occurs. 
Detailed information will be specified in the statistician analysis plan (SAP). 
12.5 
Analysis supporting secondary objectives 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) 
Efficacy 
Change from baseline to end of treatment epoch (26 weeks of treatment) in Forced Vital 
Capacity (FVC) expressed in mL will be analyzed using a similar model stated in 
Section 12.4.2 with both treatment and placebo group using non-informative prior. 
Summary statistics of change from baseline in FVC by visit and treatment will be presented. 
Progression-free survival (PFS) 
Time to progression is defined by a composite endpoint. At the end of the treatment epoch, 
the Kaplan-Meier estimates of the proportion of participants with the composite endpoint, 
along with 80% two-sided confidence intervals using Greenwood’s formula, will be 
provided. In addition, the Kaplan-Meier estimates will be plotted against time. 
The composite endpoint including ANY of the following events: 
• Absolute reduction from baseline of ≥ 10% predicted in FVC 
• Non-elective hospitalization for respiratory events 
• Lung transplant 
• Death 
Individual components of the composite endpoint will be summarized separately and if 
sufficient data is available, then further appropriate statistical analyses will be conducted. 
Incidence of absolute decline in FVC ≥ 10% predicted 
Binary output of absolute decline of ≥ 10% predicted in FVC (Yes/No) at the end of 
treatment epoch (26 weeks of treatment) will be assessed using logistic regression model 
with absolute decline of ≥ 10% (Yes/No) as dependent variable, and the treatment as 
explanatory variable. Baseline FVC%p and use of background therapy may be included as 
potential covariates. The estimated rate of the absolute decline of ≥ 10% predicted in FVC 
by treatment group and the difference between the treatment and the placebo group will be 
presented together with 90% confidence intervals. 
The number and percentage of participants with absolute decline of ≥ 10% predicted in FVC 
will be presented by epoch/visit and treatment. 

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Pulmonary physiology 
To assess the impact of the IPs on pulmonary physiology, change from baseline to the end 
of treatment epoch (26 weeks of treatment) in DLCO will be analyzed by fitting the same 
model as described for the primary endpoint in Section 12.4.2 with non-informative priors 
on both treatment arms in addition to summary statistics by treatment. 
Exercise capacity 
To assess the impact of the IPs on exercise capacity, change from baseline to the end of 
treatment epoch (26 weeks of treatment) in 6-minute walk distance will be analyzed by 
fitting the same model as described for the primary endpoint in Section 12.4.2 with 
non-informative priors on both treatment arms in addition to summary statistics by 
treatment. 
12.5.2 
Safety endpoints 
For all safety analyses, the safety set will be used. All listings and tables will be presented 
by treatment group. 
Safety summaries (tables, figures) include only data from the on-treatment period with the 
exception of baseline data which will also be summarized where appropriate (e.g. change 
from baseline summaries). In addition, a separate summary for death including on treatment 
and post treatment deaths will be provided. In particular, summary tables for adverse events 
(AEs) will be summarized from initial treatment through the end of the Safety Follow-up. 
The safety follow-up period will be a minimum of 30 days and may vary within each cohort. 
See Section 17 for details. 
Adverse events 
All information obtained on adverse events will be displayed by treatment group and 
participant. 
The number (and percentage) of participants with treatment emergent adverse events (events 
started after the first dose of study medication or events present prior to start of double-blind 
treatment but increased in severity based on preferred term) will be summarized in the 
following ways: 
• by treatment, primary system organ class and preferred term. 
• by treatment, primary system organ class, preferred term and maximum severity. 
• by treatment, Standardized MedDRA Query (SMQ) and preferred term. 
Separate summaries will be provided for study medication related adverse events, death, 
serious adverse events, other significant adverse events leading to dose suspension and/or 
discontinuation. 
Any adverse events of special interest will be outlined in Section 17. 
A participant with multiple adverse events within a primary system organ class is only 
counted once towards the total of the primary system organ class. 

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Vital signs 
All vital signs data will be listed by treatment group, subject, and epoch/visit/time and if 
ranges are available abnormalities (and relevant orthostatic changes) will be flagged. 
Summary statistics will be provided by epoch, treatment and visit/time. 
12-lead ECG 
All ECG data will be listed by treatment group, subject and epoch/visit/time, and 
abnormalities will be flagged. Summary statistics will be provided by epoch, treatment, and 
visit/time. 
Clinical laboratory evaluations 
All laboratory data will be listed by treatment group, subject, and epoch/visit/time and if 
normal ranges are available, abnormalities will be flagged. Summary statistics will be 
provided by epoch, treatment, and visit/time. Shift tables using the low/normal/high/ (low 
and high) classification will be used to compare baseline to the worst on-treatment value. 
Immunogenicity 
All immunogenicity results will be listed by treatment group, participant, and visit/time, if 
applicable within the cohort. See Section 17. 
12.5.3 
Patient reported outcomes 
L-IPF (Impacts and Symptoms Modules), K-BILD, Leicester cough, and R-Scale for IPF 
questionnaires score will be reported by treatment group, patients, and epoch/visit/time. 
Summary statistics on the change from baseline of PRO score at the end of the treatment 
epoch will be provided by treatment and visit time. 
12.6 
Analysis of exploratory endpoints 
12.6.1 
Efficacy and/or Pharmacodynamic endpoint(s) 
Disease exacerbation 
Time to IPF exacerbations or suspected exacerbations will be assessed using the statistical 
method mentioned in Section 12.5.1 “Time to event analysis”. In addition, number and 
percentage of exacerbations will be summarized by epoch/visit/treatment. 
Exploratory Progression-free survival (PFS) 
Time to progression as defined by a composite endpoint including any of the following 
events: 
· Absolute reduction from baseline of ≥ 5% predicted in FVC 
· Non elective hospitalization for respiratory events 
· Lung transplant or death 
Same statistical analysis specified in Section 12.5.1 “Time to event analysis” will be applied 
to this endpoint. 

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Pulmonary imaging 
Change from baseline to the end of treatment epoch (26 weeks of treatment) in quantitative 
high-resolution computed tomography (qHRCT) structural and functional metrics 
(interstitial fibrotic features) will be reported using summary statistics by treatment. 
12.6.2 
Pharmacokinetics 
In order to assess the pharmacokinetics of the investigational products after multiple doses, 
investigational product concentrations will be measured. 
Concentration data for each analyte in a cohort will be listed by treatment, subject, and 
epoch/visit/sampling time point. Descriptive summary statistics may be provided by visit, 
treatment and visit/sampling time point, including the frequency (n, %) of concentrations 
below the LLOQ and reported as zero. 
Summary statistics may include mean (arithmetic and geometric), standard deviation (SD), 
coefficient of variation (CV) (arithmetic and geometric), median, minimum and maximum. 
Concentrations below LLOQ will be treated as zero in summary statistics and for 
PK parameter calculations. A geometric mean will not be reported if the dataset includes 
zero values. 
Cohort specific pharmacokinetic parameters will be calculated as described in Section 17. 
Graphical presentation may be provided in addition. 
12.6.3 
PK/PD relationships 
Relationships between PK and PD variables may be explored using population PK. 
Additional statistical analysis such as analysis of variance (ANOVA) or regression analysis 
may be performed, if necessary. 
Modeling of the PK and PD data may be performed as appropriate. As the PK and PD data 
from the current study may be pooled with data from previous studies, the PK/PD analysis 
will be described and reported separately in a modeling plan and modelling report 
respectively. 
12.6.4 
Biomarkers 
Change from baseline in soluble markers (which may include but are not limited 
to 
 in the peripheral blood 
and protein profiling to explore the markers reflecting the treatment response will be 
reported using summary statistics by epoch and treatment. 
For all biomarker data (as applicable) summary statistics will be provided by cohort, 
treatment group and visit/time. As applicable, values above the upper limit of quantification 
(ULOQ) will be imputed as ULOQ in graphical summaries (with a special symbol) and for 
the calculation of the summary statistics, and values below the lower limit of quantification 
(LLOQ) will be imputed as LLOQ/2 for these analyses. The number of values outside of the 
limits of quantification will be reported in each table. All biomarker data, change from the 
baseline, percent change from baseline will be listed by cohort, treatment group, 
participants, and visit/time. Graphical summaries (including spaghetti plots, boxplots, and 
mean plots with SD) may be provided by treatment and visit/time. Values below the LLOQ 
will be imputed as LLOQ/2 for these analyses. The number of values outside of the limits 
of quantification will be reported in each table.  
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. 
12.6.5 
DNA 
Exploratory DNA studies are designed to investigate the association between genetic factors 
(genotypes) and clinical assessments (phenotypes) which are collected during the clinical 
trial. Without prior evidence of a strong association, a number of possible associations are 
evaluated with exploratory analyses. A range of statistical tests are used for the analyses. 
Additional data, from other clinical trials, are often needed to confirm associations. 
Alternatively, if the number of participants enrolled in the study is too small to complete 
proper statistical analyses, the data may be combined, as appropriate, with those from other 
studies to enlarge the dataset for analysis. 
Data generated on hypothesis-free platforms will be reported separately (e.g. CSR 
addendum). 
12.7 
Interim analyses 
In addition to those listed below, other interim analyses may be conducted to support 
decision making concerning the current clinical study, the sponsor’s clinical development 
projects in general or in case of any safety concerns. 
12.7.1 
Cohort Completion Analyses 
Data will be analyzed at the completion of each cohort in the trial. 
Cohort completion analyses are planned when participants complete each cohort (End of 
Treatment). The unblinded analysis results including efficacy and safety assessment will be 
reviewed by the clinical team and further shared with Novartis teams and members of the 
DMC. The data will be used to determine if the noted efficacy was sufficient to allow early 
transition of the respective IP to a later stage study. 
12.7.2 
Within each cohort 
Interim analyses are planned when sufficient participants complete their 26-week 
post-treatment assessments in each cohort (approximately 50%). Data from participants who 
have completed their 26‑week post-treatment assessment and data from participants who 
have not completed the treatment epoch but have post-treatment assessments at the time of 
the IA will be included. The purpose of this unblinded IA is to assess early efficacy and to 
assess futility. The key endpoint to be evaluated at this IA will be the change from baseline 
in FVC %predicted. 
There will be no pause in enrollment at the time of interim analysis, and participants may 
continue to be enrolled until the interim analysis is complete. 
The Bayesian posterior probability of the treatment effect (treatment – placebo) will be 
calculated for the endpoint. If there is more than 60% probability that the treatment effect at 
the end of treatment epoch (26 weeks of treatment) is <0 (treatment worse than placebo), 
then this will act as evidence to suggest that the investigational product has not had a 
beneficial effect on the endpoint in this population. This data, together with other key 
endpoints, will be used to assess whether the cohort could be stopped for futility. 
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Similarly, if there is enough information at this interim analysis to conclude that there is 
90% posterior probability that the treatment effect is >0 (treatment better than placebo) in 
the endpoint, and there is 50% posterior probability of the treatment effect > 1.3%, then this 
information, together with other key endpoints, will be used to consider early evidence of 
efficacy and decision of launching later stage of the clinical trials for the respective 
investigational product. 
If the study is not stopped for futility or for early evidence of efficacy at the time of the IA, 
the cohort will continue until all participants have completed the cohort. 
Within cohort IAs, unblinded interim analysis results will be reviewed by the clinical team. 
The clinical team may communicate interim results (e.g. evaluation of efficacy criteria or 
information needed for planning/modifying another study) to relevant Novartis teams and 
members of the DMC. 
No further dissemination of interim results should occur, in particular not with individuals 
involved in treating the study’s participants or assessing clinical data (e.g. ECGs, images, 
symptoms) obtained in the study.  
12.8 
Sample size calculation 
12.8.1 
Primary endpoint(s) 
Without considering the drop-off rate,40 participants per active treatment group and at least 
40 participants on placebo of each cohort will give at least 80% power to detect a treatment 
improvement in change from baseline in FVC%p (treatment – placebo) for at least 2% in 
patients with IPF assuming the standard deviation is around 5%. 
The sample size calculation is based on the primary efficacy endpoint of change from 
baseline in FVC%p at week 26. The criteria for this calculation aimed for a 90% level of 
proof that difference in change in FVC%p from baseline to week 26 between treatment and 
placebo and the mean treatment effect is at least 1.3% better than placebo effect with 
50% probability. The former targets proof that the treatment produces a statistically 
significant improvement in change from baseline in FVC, while the latter targets proof of 
clinical relevance. 
The sample size calculation also takes into account the interim analysis step with futility and 
early efficacy criteria defined in Section 12.7. The overall type I error at the end of study 
will be approximately 13%. 
Additional participants may be enrolled if more than 15% of the planned randomized 
participants have not completed the 26 weeks of treatment, as per protocol requirements. 
Prior to enrolling additional participants, a DMC review of safety data will occur to ensure 
there are no tolerability/safety issues that would advise against enrolling additional 
participants. 
Refer to Section 17 for cohort specific sample size after considering drop off rate and 
randomization ratio between the treatment group and placebo group. 
12.8.2 
Secondary endpoint(s) 
Not applicable. 

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13 
Ethical considerations and administrative procedures 
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed, and reported in 
accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with 
applicable local regulations (including European Directive 2001/20/EC or European 
Clinical Trial Regulation 536/2014, US CFR 21), and with the ethical principles laid down 
in the Declaration of Helsinki. 
13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial 
protocol, written informed consent form, consent form updates, participant recruitment 
procedures (e.g. advertisements) and any other written information to be provided to 
participants. Prior to study start, the investigator is required to sign a protocol signature page 
confirming his/her agreement to conduct the study in accordance with these documents and 
all of the instructions and procedures found in this protocol and to give access to all relevant 
data and records to Novartis monitors, auditors, Novartis Quality Assurance representatives, 
designated agents of Novartis, IRBs/IECs, and regulatory authorities as required. If an 
inspection of the clinical site is requested by a regulatory authority, the investigator must 
inform Novartis immediately that this request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov 
and as required in EudraCT or CTIS public website. In addition, after cohort completion 
(defined as cohort last participant last visit) and finalization of the cohort study report the 
results of this trial will be submitted for publication and posted in a publicly accessible 
database of clinical trial results, such as the Novartis clinical trial results website and all 
required Health Authority websites (e.g. Clinicaltrials.gov, EudraCT or CTIS public website 
etc.). 
Summary results of primary and secondary endpoints will be disclosed based upon the 
global Last Participant Last Visit (LPLV) date, since multinational studies are locked and 
reported based upon the global LPLV. 
For details on the Novartis publication policy including authorship criteria, please refer to 
the Novartis publication policy training materials that were provided to you. 
Any data analysis carried out independently by the Investigator must be submitted to 
Novartis before publication or presentation. 
13.4 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control, to ensure compliance with written 
Standard Operating Procedures as well as applicable global/local GCP regulations and ICH 
Guidelines. 
Audits of investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring, or performing quality control 
of the clinical trial. The clinical audit process uses a knowledge/risk-based approach. 

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Audits are conducted to assess GCP compliance with global and local regulatory 
requirements, protocols, and internal SOPs, and are performed according to written Novartis 
processes. 
13.5 
Participant Engagement 
The following participant engagement initiatives are included in this study and will be 
provided, as available, for distribution to study participants. If compliance is impacted by 
cultural norms or local laws and regulations, sites may discuss modifications to these 
requirements with Novartis. 
• Thank You card 
• Treatment information 
• Plain language trial summary 
14 
Protocol adherence 
This protocol defines the study objectives, the study procedures, and the data to be collected 
on study participants. Additional assessments required to ensure safety of participants 
should be administered as deemed necessary on a case-by-case basis. Under no 
circumstances including incidental collection is an investigator allowed to collect additional 
data or conduct any additional procedures for any purpose involving any investigational 
drugs under the protocol, other than the purpose of the study. If despite this interdiction 
prohibition, data, information, observation would be incidentally collected, the investigator 
shall immediately disclose it to Novartis and not use it for any purpose other than the study, 
except for the appropriate monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by 
Novartis and approved by the IRB/IEC and Health Authorities, where required, it cannot be 
implemented. 
14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment 
that must be approved by Novartis, health authorities where required, and the IRB/IEC prior 
to implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any participant included in 
this study, even if this action represents a deviation from the protocol. In such cases, 
Novartis should be notified of this action and the IRB/IEC at the study site should be 
informed according to local regulations. 

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15 
References 
References are available upon request 
Bitterman DS, Cagney DN, Singer LL, et al (2020) Master Protocol Trial Design for 
Efficient and Rational Evaluation of Novel Therapeutic Oncology Devices. J Natl Cancer 
Inst; 112(3):229-37. 
Collard HR, Ryerson CJ, Corte TJ, et al (2016) Acute Exacerbation of Idiopathic 
Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med; 
194(3):265-75. 
du Bois RM (2010) Strategies for treating idiopathic pulmonary fibrosis. Nat Rev Drug 
Discov; 9(2):129-40. 
Fischer A, Antoniou KM, Brown KK, et al (2015) An official European Respiratory 
Society/American Thoracic Society research statement: interstitial pneumonia with 
autoimmune features. Eur Respir J; 46(4):976-87. 
Graham BL, Brusasco V, Burgos F, et al (2017) 2017 ERS/ATS standards for single-
breath carbon monoxide uptake in the lung. Eur Respir J; 49(1):1600016. 
Graham BL, Steenbruggen I, Miller MR, et al (2019) Standardization of Spirometry 2019 
Update. An Official American Thoracic Society and European Respiratory Society 
Technical Statement. Am J Respir Crit Care Med; 200(8):e70-e88. 
Holland AE, Spruit MA, Troosters T, et al (2014) An official European Respiratory 
Society/American Thoracic Society technical standard: field walking tests in chronic 
respiratory disease. Eur Respir J; 44(6):1428-46. 
Hutchinson J, Fogarty A, Hubbard R, et al (2015) Global incidence and mortality of 
idiopathic pulmonary fibrosis: a systematic review. Eur Respir J; 46(3):795-806. 
King TE, Bradford WZ, Castro-Bernardini S, et al (2014) A phase 3 trial of pirfenidone in 
patients with idiopathic pulmonary fibrosis. N Engl J Med; 370(22):2083-92. 
Lee HE, Myong JP, Kim HR, et al (2016) Incidence and prevalence of idiopathic 
interstitial pneumonia and idiopathic pulmonary fibrosis in Korea. Int J Tuberc Lung Dis; 
20(7):978-84. 
Lynch JP, Huynh RH, Fishbein MC, et al (2016) Idiopathic Pulmonary Fibrosis: 
Epidemiology, Clinical Features, Prognosis, and Management. Semin Respir Crit Care 
Med; 37(3):331-57. 
Nalysnyk L, Cid-Ruzafa J, Rotella P, et al (2012) Incidence and prevalence of idiopathic 
pulmonary fibrosis: review of the literature. Eur Respir Rev; 21(126):355-61. 
Raghu G, Collard HR, Egan JJ, et al (2011) An official ATS/ERS/JRS/ALAT statement: 
idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. 
Am J Respir Crit Care Med; 183(6):788-824. 
Raghu G, Remy-Jardin M, Myers JL, et al (2018a) Diagnosis of Idiopathic Pulmonary 
Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit 
Care Med; 198(5):e44-e68. 

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Raghu G, van den Blink B, Hamblin MJ, et al (2018b) Effect of Recombinant Human 
Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic 
Pulmonary Fibrosis: A Randomized Clinical Trial. JAMA; 319(22):2299-307. 
Richeldi L, du Bois RM, Raghu G, et al (2014) Efficacy and safety of nintedanib in 
idiopathic pulmonary fibrosis. N Engl J Med; 370(22):2071-82. 
Sgalla G, Iovene B, Calvello M, et al (2018) Idiopathic pulmonary fibrosis: pathogenesis 
and management. Respir Res; 19(1):32. 
Song JW, Hong SB, Lim CM, et al (2011) Acute exacerbation of idiopathic pulmonary 
fibrosis: incidence, risk factors and outcome. Eur Respir J; 37(2):356-63. 
Woodcock J, LaVange LM (2017) Master Protocols to Study Multiple Therapies, Multiple 
Diseases, or Both. N Engl J Med; 377(1): 62-70. 

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16 
Appendices 
16.1 
Appendix 1: Liver event and laboratory trigger definitions & 
follow-up requirements 
Table 16-1 
Liver event and laboratory trigger definitions 
  
Definition/ threshold 
Liver laboratory triggers 
If ALT, AST, and total bilirubin normal at 
baseline: 
• 
ALT or AST > 5 × ULN 
• 
ALP > 2 × ULN (in the absence of known 
bone pathology) 
• 
Total bilirubin > 3 × ULN (in the absence 
of known Gilbert syndrome) 
• 
ALT or AST > 3 × ULN and INR > 1.5 
• 
Potential Hy’s Law cases (defined as ALT 
or AST > 3 × ULN and Total bilirubin > 2 × 
ULN [mainly conjugated fraction] without 
notable increase in ALP to > 2 × ULN) 
• 
Any clinical event of jaundice (or 
equivalent term) 
• 
ALT or AST > 3 × ULN accompanied by 
(general) malaise, fatigue, abdominal pain, 
nausea, or vomiting, or rash with 
eosinophilia 
• 
Any adverse event potentially indicative of 
a liver toxicity 
If ALT or AST abnormal at baseline: 
• 
ALT or AST > 3x baseline or > 300 U/L 
(whichever occurs first) 

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Table 16-2 
Follow up requirements for liver laboratory triggers - ALT, AST, 
TBL 
ALT  
TBL  
Liver Symptoms  
Action  
ALT increase without bilirubin increase:  
If normal at baseline:  
ALT > 3 x ULN  
Normal  
For participants with 
Gilbert’s syndrome: No 
change in baseline TBL  
None 
• 
No change to study 
treatment  
• 
Measure ALT, AST, 
ALP, GGT, TBIL, INR, 
albumin, CK, and 
GLDH in 48-72 hours.  
• 
Follow-up for 
symptoms.  
If elevated at baseline:  
ALT > 2 x baseline  
or > 300 U/L (whichever 
occurs ﬁrst)  
If normal at baseline:  
ALT > 5 x ULN for more 
than two weeks  
Normal  
For participants with 
Gilbert’s syndrome: No 
change in baseline TBL  
None 
  
• 
Measure ALT, AST, 
ALP, GGT, TBIL, INR, 
albumin, CK, and 
GLDH in 48-72 hours.  
• 
Follow-up for 
symptoms.  
• 
Initiate close 
monitoring and workup 
for competing 
etiologies.  
• 
Study drug can be 
restarted only if 
another etiology is 
identiﬁed and liver 
enzymes return to 
baseline.  
If elevated at baseline:  
ALT > 3 x baseline  
or > 300 U/L (whichever 
occurs ﬁrst) for more 
than two weeks  
If normal at baseline:  
ALT > 8 x ULN  
Normal  
None 
ALT increase with bilirubin increase:  
If normal at baseline:  
ALT > 3 x ULN  
TBL > 2 x ULN (or 
INR > 1.5)  
For participants with 
Gilbert’s syndrome: 
Doubling of direct 
bilirubin  
None 
• 
Discontinue study 
drug 
If elevated at baseline:  
ALT > 2 x baseline  
or > 300 U/L (whichever 
occurs ﬁrst)  
If normal at baseline:  
ALT > 3 x ULN  
Normal or elevated  
Severe fatigue, 
nausea, vomiting, 
right upper quadrant 
pain  
If elevated at baseline:  
ALT > 2 x baseline  
or > 300 U/L (whichever 
occurs ﬁrst) 

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Table 16-3 
Isolated total bilirubin elevation 
Criteria 
Recommendation 
Any elevation > ULN 
Fractionate bilirubin, evaluate for cholestatic liver injury (ALP) or 
alternative causes of bilirubin elevation (e.g. disease 
progression [imaging]). Treat alternative causes according to 
local institutional guidelines. 
Grade 2 (>1.5 – 3.0 ULN) 
Maintain treatment. Repeat LFTs within 48-72 hours, then 
monitor LFTs weekly until resolution to ≤ Grade 1 or to 
baseline  
Grade 3(>3.0 - 10 ULN) 
Interrupt treatment. Repeat LFTs within 48-72 hours, then 
monitor LFTs weekly until resolution to ≤ Grade 1 or to baseline 
Grade 4(>10 x ULN) 
Discontinue study treatment 
Based on investigator’s discretion investigation(s) for contributing factors for the liver event 
can include serology tests, imaging and pathology assessments, hepatologist’s consultancy; 
obtaining more detailed history of symptoms and prior or concurrent diseases, history of 
concomitant drug use, exclusion of underlying liver disease. 

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16.2 
Appendix 2: Specific Renal Alert Criteria and Actions and 
Event Follow-up 
Table 16-4 
Specific Renal Alert Criteria and Actions 
Serum Event 
 
Serum creatinine increase > 2-fold compared 
to baseline 
Consider causes and possible interventions  
Follow up within 2-5 days 
Urine Event 
 
New onset dipstick proteinuria >=+3 OR 
Consider causes and possible interventions 
Assess serum albumin & serum total protein 
Repeat assessment to confirm 
Consider drug interruption or discontinuation 
unless other causes are diagnosed and 
corrected 
New onset dipstick hematuria >=+3 
Repeat assessment to confirm 
Distinguish hemoglobinuria from hematuria 
Urine sediment microscopy 
Assess serum Creatinine 
Exclude infection, trauma, bleeding from the 
distal urinary tract/bladder, menstruation 
Consider bleeding disorder 
For all renal events: 
  
Document contributing factors in the CRF: co-
medication, other co-morbid conditions, and 
additional diagnostic procedures performed 
  
Monitor subject regularly (frequency at 
investigator's discretion) until either: 
  
Event resolution: sCr within 20% of baseline or 
  
Event stabilization: sCr level with +-20% 
variability over last 2 months 
  

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17 
Cohort Specific Information 
This section contains details that pertain to specific cohorts and should be considered as 
supplementary to information presented in the preceding core protocol sections and 
respective Investigator Brochures or country-specific product labels for marketed 
investigational products. If there are no cohort- or treatment-specific details presented for a 
given topic (e.g. cohort- or treatment-specific eligibility criteria, study restrictions, food 
effects, etc.), the information in the corresponding section in the core protocol for that topic 
should be implemented without further adjustment. 
17.1 
Cohort 1 LTP001 
Cohort 1 will assess the safety and efficacy of LTP001 in participants with mild to moderate 
IPF. 
Approximately 94 patients will be randomized in a 1:1 ratio to one of the following 
treatment arms: 
• Arm 1: LTP001  mg 
 
• Arm 2: Matching placebo 
Figure 17-1 
Cohort 1 Study Design 
 
17.1.1 
Introduction 
This cohort will evaluate LTP001. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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17.1.2 
Background 
 
 
 
Preclinical Data 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Data 
 
 
 
 
 
 
 
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Dosing Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
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Additional details about dosing and potential risks of LTP001 can be found in the 
Investigator's Brochure. 
Procedural risks 
 
 
 
 
Potential Benefits 
 
 
 
 
17.1.3 
Study Treatment 
 
 
 
 
 
 
Table 17-1 
  
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17.1.4 
Specific Exclusion Criteria 
101. Women of child-bearing potential (WOCBP), defined as all women physiologically 
capable of becoming pregnant, unless they are using highly effective methods of 
contraception for 3 months prior to screening, during dosing, and until End of Study visit 
(30 days post last treatment). Highly effective contraception methods include: 
• Total abstinence (when this is in line with the preferred and usual lifestyle of the 
participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception. 
• Bilateral tubal ligation, surgical bilateral oophorectomy with or without hysterectomy, 
total hysterectomy, or bilateral salphingectomy at least six weeks before taking study 
treatment.  In case of oophorectomy alone, only when the reproductive status of the 
woman has been confirmed by follow up hormone level assessment is not considered 
to be of child-bearing potential. 
• Male sterilization (at least 6 months prior to screening). For female participants on the 
study, the vasectomized male partner should be the sole partner for that participant. 
• Use of oral, (estrogen and progesterone), injected, or implanted hormonal methods of 
contraception or placement of an intrauterine device (IUD) or intrauterine system 
(IUS), or other forms of hormonal contraception that have comparable efficacy (failure 
rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.  
In case of use of oral contraception women should have been stable on the same pill for a 
minimum of 3 months before taking study treatment. 
102. Sexually active males must use a condom during intercourse while taking drug and for 
24 hours after stopping study medication and should not father a child in this period. 
A condom is required to be used also by vasectomized men in order to prevent delivery of 
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the drug via seminal fluid. In addition, male participants should not donate sperm while 
taking drug and for 24 hours after stopping study medication. 
 
17.1.5 
Specific Restrictions for Study Participants 
No specific restrictions for the LTP001 cohort. 
17.1.5.1 Prohibited Medications 
Use of the treatments displayed in the below table are not allowed. 
Table 17-2 
 
17.1.6 
Permitted concomitant therapy requiring caution and/or action 
Not applicable for LTP001. 
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17.1.7 
 
 
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Table 17-3 
 
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17.1.8 
Pharmacokinetics 
PK samples will be collected at the visits defined in Table 17-3. Follow instructions outlined in 
the laboratory manual regarding sample collection, numbering, processing and shipment. 
See the potential use of residual samples for more information. 
In order to better define the PK profile, the timing of the PK sample collection may be altered 
based on emergent data. 
PK samples will only be evaluated in participants on active treatment. 
LTP001 will be determined by a validated LC-MS/MS method; the anticipated Lower Limit of 
Quantification (LLOQ) is 0.05 ng/mL. 
Concentrations will be expressed in mass per volume units and will refer to the free base. 
Concentrations below the LLOQ will be reported as “zero” and missing data will be labeled as 
such in the Bioanalytical Data Report. 
17.1.8.1 Pharmacokinetic analytical method(s) 
Descriptive summary of LTP001 plasma concentration data will be provided by treatment, and 
visit/sampling time point, including the frequency (n, %) of concentrations below the LLOQ 
and reported as zero. 
Summary statistics will include mean (arithmetic and geometric), SD, CV (arithmetic and 
geometric), median, minimum, and maximum. 
Descriptive summary statistics will include mean (arithmetic and geometric), SD, and CV 
(arithmetic and geometric), median, minimum, and maximum. 
Appropriate PK parameters e.g. Cmax, Tmax, and partial AUCs may be assessed using non-
compartmental analysis (Certara Phoenix). The sparse sampling may limit potential parameter 
estimation. A population PK model may also be used for PK analysis. 
17.1.9 
Exploratory Biomarkers 
Sample(s) will be collected at the time point(s) defined in the Assessment Schedule 
(Table 17-3). The list may be changed or expanded further, as it is recognized that more relevant 
or novel biomarkers may be discovered during the conduct of the study. Follow instructions for 
sample collection, numbering, processing, and shipment provided in the laboratory manual. 
Target engagement markers of LTP001 may include but are not limited to 
 
). 
RNA sequencing 
The expression of targeted genes will be examined using RNA (or other nucleic acid) analytical 
technologies, such as expression microarrays, polymerase chain reaction, Nanostring, Next 
Generation Sequencing techniques, or others.  
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17.1.10 Specific Study Design Considerations 
The post-treatment safety follow-up in Cohort 1 will be 30 (+14) days following the last drug 
administration. 
   
 
 
 
 
 
 
Table 17-4 
LTP001 Specific Safety Assessments 
Test Category 
Test Name 
Thyroid 
Triiodothyronine, Free/Total Thyroxine, Thyroid 
stimulating hormone 
Endocrine Function Tests 
Aldosterone, Cortisol, Insulin-like growth factor 1, 
Adrenocorticotropic hormone, Testosterone  
17.1.11 Statistical considerations 
17.1.11.1   Sample size calculation 
As the first cohort in this platform study, the randomization ratio between the treatment group 
and placebo group is determined as 1:1. Assuming the drop-off rate of 15% Raghu et al 2018b, 
47 patients will be randomized into each treatment group with a total of 94 patients for this 
cohort. The sensitivity of power to changes in assumptions with different drop off rate is listed 
in Table 17-5. 
Table 17-5 
Sensitivity of power to changes in assumptions for N=47 per group 
True treatment 
difference for 
LTP001 vs Placebo 
(%) 
Power for primary endpoint (type I error around 10%) 
With 10% drop-out 
rate (38 per group) 
With 15% drop-out 
rate (40 per group) 
With 20% drop-out 
rate (43 per group) 
1.6 
1.8 
2 
2.2 
2.4 
64% 
72% 
79% 
84% 
89% 
65% 
72% 
79% 
85% 
89% 
65% 
73% 
80% 
85% 
90% 
 
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