Conditions: Idiopathic Pulmonary Fibrosis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 123
Healthy volunteers: no

Brief summary:
A phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety, tolerability, biological activity, and pharmacokinetics (PK) of ND-L02-s0201 for Injection in subjects with IPF.

Detailed description:
All subjects were treated with ND-L02-s0201 or placebo for 24 weeks (a total of 12 doses). Subject's participation in the study was approximately 40 weeks including a Screening and Baseline period of up to 6 weeks, a treatment period of 24 weeks (including the 2 weeks after the last study treatment), and a follow-up period of 10 weeks after End-of-Treatment (EOT).

Arms:
arm 1: ND-L02-s0201 45mg arm 2: ND-L02-s0201 90mg arm 3: Control Arm

Interventions: intervention 1: ND-L02-s0201 (Low Dose) intervention 2: ND-L02-s0201 (High Dose) intervention 3: Other: Placebo
Intervention descriptions: intervention 1: Intravenous administration every 2 weeks intervention 2: Intravenous administration every 2 weeks intervention 3: Saline

Protocol document:
Prot_000.pdf: 
Document Type:  
Final Protocol 
Document Date:  
17 June 2020 
Study Title:  
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety, Tolerability, Biological Activity, and PK of 
ND-L02-s0201 in Subjects with Idiopathic Pulmonary Fibrosis (IPF) 
Protocol Reference Number: ND-L02-S0201-005 
NCT Number: NCT03538301 
 
 


A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED STUDY TO EVALUATE THE SAFETY, 
TOLERABILITY, BIOLOGICAL ACTIVITY, AND PK OF 
ND-L02-S0201 IN SUBJECTS WITH IDIOPATHIC 
PULMONARY FIBROSIS (IPF) 
 
PROTOCOL NUMBER: ND-L02-S0201-005 
EUDRACT NUMBER: 2017-004919-39 
 
Product: 
ND-L02-s0201 for Injection 
Sponsor: 
Nitto Denko Corporation 
1-1-2, Shimohozumi, Ibaraki 
Osaka 567-8680, Japan 
Sponsor’s Authorized 
Representative: 
 
 
 
 
 
 
Medical Monitor: 
 
 
 
 
 
Date of Protocol: 
20 October 2017 
Amendment 01: 
18 January 2018 
Amendment 02: 
12 March 2018 
Amendment 03: 
08 July 2019 
Amendment 04: 
18 September 2019 
Amendment 05: 
17 June 2020 
Confidentiality Statement 
This confidential information in this document is provided to you as an Investigator or consultant for review by you, 
your staff, and the applicable Institutional Review Board/Independent Ethics Committee. Your acceptance of this 
document constitutes agreement that you will not disclose the information contained herein to others without written 
authorization from the Sponsor. 


Clinical Protocol: Study ND-L02-s0201-005 
Amendment 05 
1. 
SIGNATURE PAGE 
1.1. 
Sponsor Approval 
Protocol Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study 
to Evaluate the Safety, Tolerability, Biological Activity, and PK of 
ND-L02-s0201 in Subjects with Idiopathic Pulmonary Fibrosis 
(IPF) 
Protocol Number: 
ND-L02-s0201-005 
Date of Amendment 05: 
17 June 2020 
This study will be conducted in compliance with the clinical study protocol and amendments, 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) Guideline for current Good Clinical Practice (GCP) and applicable regulatory 
requirements. Compliance with GCP standards provides public assurance that the rights, safety, 
and wellbeing of trial subjects are protected, consistent with the principles that have their origin 
in the Declaration of Helsinki. 
17 June 2020 
2 


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1.2. 
Investigator Agreement 
Protocol Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Safety, Tolerability, Biological Activity, 
and PK of ND-L02-s0201 in Subjects with Idiopathic 
Pulmonary Fibrosis (IPF) 
Protocol Number: 
ND-L02-s0201-005 
Date of Amendment 05: 
17 June 2020 
 
By signing this page, I attest that I have read and understand the contents of Clinical Protocol 
ND-L02-s0201-005. I agree to adhere to the design, conduct, and reporting requirements of the 
study as stated in the clinical protocol and to my obligations to the Sponsor as described in the 
protocol and executed contracts between myself, my Institution, and the Sponsor. 
 


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4 
 
 
2. 
SYNOPSIS 
Name of Sponsor 
Nitto Denko Corporation 
Name of Investigational Product 
ND-L02-s0201 for Injection (ND-L02-s0201) 
Name of Active Ingredient 
NDT-05-0038 
Title of Study 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, 
Tolerability, Biological Activity, and PK of ND-L02-s0201 in Subjects with Idiopathic Pulmonary 
Fibrosis (IPF) 
Study Number  
ND-L02-s0201-005 
Study Centers 
Multicenter  
Phase of Development 
2 
Objectives 
Primary: 
• 
Evaluate the safety and tolerability of ND-L02-s0201, administered at 2 dose levels, once 
every 2 weeks (Q2W) over 24 weeks, versus placebo, in conjunction with standard of care 
(SOC) 
Secondary: 
• 
Evaluate the biological activity of ND-L02-s0201 as measured by spirometry over 24 weeks 
• 
Evaluate changes of interstitial lung abnormalities (ILA) as measured by high-resolution 
computed tomography (HRCT)  
• 
Evaluate single-dose pharmacokinetic (PK) endpoints over 24 weeks in a subset of subjects 
• 
Evaluate trough levels for accumulation over time and identify when steady state conditions 
are achieved 
Methodology 
This is a Phase 2, double-blind, placebo-controlled, randomized, multicenter, international study of 
2 doses of ND-L02-s0201 for Injection to evaluate safety, tolerability, biological activity, and PK in 
subjects with a diagnosis of IPF with forced vital capacity (FVC) ≥ 45% of predicted and diffusion 
capacity of the lung for carbon monoxide (DLCO) ≥ 30% of predicted and who meet all inclusion 
criteria and do not meet any exclusion criteria.  
Two dose levels of ND-L02-s0201 will be evaluated: a low dose (45 mg) and a high dose (90 mg). 
Subjects will be randomly assigned to receive ND-L02-s0201 for Injection or placebo Q2W over a 
24-week treatment period. Approximately 120 eligible subjects will be randomized 1:1:1 to 1 of 
3 treatment arms: ND-L02-s0201 for Injection high dose (90 mg), ND-L02-s0201 for Injection low 
dose (45 mg), or placebo. 


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For the purposes of this trial, SOC is defined as administration of either nintedanib or pirfenidone, 
though not both. Alternatively, eligible subjects do not need to be on either medication. For subjects 
in Germany only (due to country specific medical practice and guidelines), subjects do not need to be 
on either medication, provided they have failed or not tolerated nintedanib and/or pirfenidone. 
Subjects receiving SOC at the time of enrollment in the study will be stratified across the 3 treatment 
arms via the interactive web response system (IWRS). As there is no minimum number of subjects for 
a given SOC stratum, balance in strata across the 3 treatment arms is required.  
Discontinuation of either nintedanib or pirfenidone must have occurred at least 12 weeks before 
Visit 1a. If the subject has been taking either pirfenidone or nintedanib before Visit 1a, the same 
medication should be continued during the subject’s participation in this trial. However, dose 
adjustment or discontinuation of SOC in accordance with the prescribing information is permitted if 
clinically indicated. If the subject is not taking either pirfenidone or nintedanib at Visit 1a, neither 
medication may be taken through Week 24 (Visit 14) or Early Termination (ET). No other 
investigational therapy for IPF is allowed within 8 weeks or 5 half-lives (whichever is longer) before 
Visit 1a. 
Pharmacokinetics: 
 
 
 
 
  
 
Number of Subjects (planned) 
Approximately 120 subjects will be enrolled into the study, with approximately 40 subjects in each of 
3 arms. 
 
 
Inclusion Criteria 
To be randomized, all subjects must meet the criteria listed below. 
1. Males and females between 40 and 80 years of age, inclusive, at the time of consent. 
2. Diagnosis of IPF within 5 years before Visit 1a, confirmed by the Principal Investigator (PI) 
using American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese 
Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines (Raghu 
et al, 2011 or Raghu et al, 2018; see Section 11.2.5). 
a. Clinical management of the patient at the site must be for IPF and the PI must be 
convinced that all locally available information support UIP/IPF is the most likely 
diagnosis. It is mandatory that the PI consider overreader interpretation of Visit 1b 
HRCT and, if performed, SLB in order to determine that a subject is eligible for this 
trial. 
3. Extent of fibrosis greater than emphysema on HRCT. 
4. If on pirfenidone or nintedanib, unchanged dose for at least 12 weeks before Visit 1a. 
Subjects may not be on both pirfenidone and nintedanib. 


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5. FVC ≥ 45% of predicted.  
6. DLCO corrected for hemoglobin ≥ 30% of predicted value. 
7. Pulse oximetry saturation ≥ 90%, at rest while breathing ambient air or ≤ 2 L/minute 
supplemental oxygen by nasal prongs/cannula (Section 11.2.1). 
8. Ratio of forced expiratory volume in 1 second (FEV1) to FVC ≥ 0.70. 
9. Adequate liver and renal function, as demonstrated by: 
• 
Total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless participant has a 
documented history of Gilbert’s syndrome 
• 
Aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 × ULN 
• 
Creatinine < 2 × ULN 
• 
Serum albumin > 3.5 g/dL 
10. Life expectancy of ≥ 12 months.  
 
12. Women of childbearing potential (WCBP) must be willing to use a highly effective method of 
contraception throughout the study and study follow up or for at least 90 days after the last 
dose of study treatment (refer to Section 10.3.2.3). 
13. Women must be willing not to breastfeed for 90 days after the last dose of the study 
treatment. 
14. Males must agree to use a condom throughout the study and for 90 days after the last dose of 
study treatment to prevent seminal transmission of the investigational product (IP). 
15. Males with female partners of childbearing potential must agree to use a highly effective 
method of contraception (refer to Section 10.3.2.3) throughout the study and for 90 days after 
the last dose of study treatment. All men with female partners of childbearing potential will 
be instructed to contact the Investigator immediately if their partner becomes pregnant at any 
time during study participation. All men must agree not to donate semen throughout the study 
and for 90 days after the last dose of study treatment. 
16. Willing and able to provide written informed consent and comply with the study procedures 
and visit schedule, including follow-up visits. 
Exclusion Criteria 
Potential subjects who meet any of the following criteria at Screening will be excluded from the 
study: 
1. Best, acceptable FVC from separate Screening spirometry that differ by ≥ 200 mL. See 
Section 8.3.1 for more information. 
2. Respiratory exacerbation(s) or hospitalization for IPF exacerbation within 3 months before 
Visit 1a. 
3. Taking both pirfenidone and nintedanib concurrently within 12 weeks before Visit 1a. 
4. Anticipated to receive a lung transplant during the subject’s participation in the study. 
5. Diagnosis of any connective tissue disease with a natural history that may be associated with 
pulmonary disease. 
6. Clinical evidence of or known history of cirrhosis. 
 
8. Uncontrolled cardiac disease or cardiac surgical procedure (eg, New York Heart Association 
Class III or IV, myocardial infarction, transient ischemic attack, uncontrolled atrial or 


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7 
 
 
ventricular cardiac arrhythmias, unstable angina, stroke, coronary angioplasty, coronary 
artery bypass graft) within 30 days before Visit 1a. 
9. Active smoker or smoking cessation within 12 weeks before Visit 1a. 
10. Malignancy within the last 5 years, with the exception of curable cancer (eg, basal or 
squamous cell skin cancer, cervical cancer in situ, nonmedullary thyroid carcinoma) that has 
been adequately treated (eg, excision). 
11. Evidence of any unstable or untreated, clinically significant disease or condition that, in the 
opinion of the Investigator, might confound the interpretation of the study or place the subject 
at increased risk (eg, uncontrolled hypertension, diabetes mellitus). Subjects will have to have 
been on stable treatment for at least 4 weeks before Visit 1a. 
12. Treatment with high dose corticosteroids, cytotoxic agents (eg, chlorambucil, azathioprine, 
cyclophosphamide, methotrexate), unapproved IPF-targeted therapy, and cytokine 
modulating agents within 8 weeks or 5 half-lives (whichever is longer) before Visit 1a. 
• 
A dose of ≤ 15 mg/day prednisone, or equivalent, is acceptable if unchanged for 
≥ 10 weeks before Visit 1a and is expected to remain unchanged during the subject’s 
participation in the study. 
13. Receiving an investigational treatment, whether or not approved for marketing, with the last 
dose of that study drug within 8 weeks or 5 half-lives (whichever is longer) before Visit 1a. 
Individuals allocated to receive no treatment beyond SOC in an investigational study are not 
excluded from this trial. 
14. History of allergic reaction to any of the study drugs to be administered. 
15. Pregnant or breastfeeding. 
16. Veins unsuitable for repeated venipuncture or intravenous (IV) infusion (eg, veins that are 
difficult to locate, access, or puncture; veins with a tendency to rupture during or after 
puncture), in the opinion of study center personnel. 
17. Known history of human immunodeficiency virus (HIV) infection, active chronic hepatitis B 
(eg hepatitis B surface antigen positive), and/or untreated hepatitis C antigen positive patients 
(with or without abnormal liver enzymes). If treated for hepatitis C viral eradication, then a 
viral load below the limits of quantitative detection for at least 12 weeks must be 
documented. 
18. History of alcohol abuse and/or dependence within the last 2 years, as determined by the 
Investigator. 
19. History within the last 2 years of significant mental illness, or dependence on any opioid or 
illicit drugs as defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition 
(DSM-5). 
20. Suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
infection, defined as meeting one or more of the following criteria: 
a. The subject has known exposure to a person with signs or symptoms of SARS-CoV-2 
infection or has tested positive for SARS-CoV-2 (suggesting current infection) within 
21 days prior to the subject’s Visit 1a. 
b. The subject has current signs and symptoms suggestive of SARS-CoV-2 infection. 
c. The subject has SARS-CoV-2 virus or viral antigen detected at Visit 1a using a test 
approved for marketing if testing is available. (Detection of antibody to SARS-CoV-2 
will not be exclusionary. Refer to Section 8.3.3.1 for more guidance on SARS-CoV-2 
testing.) 


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Screening and Rescreening Procedures 
Refer to Section 8.3 for additional information on Screening and Rescreening procedures. Refer to 
Section 18.6 for guidance on clinical trial conduct relating to coronavirus disease (COVID-19). 
Investigational Product, Dosage, and Mode of Administration 
ND-L02-s0201 will be administered by IV infusion at either 45 mg or 90 mg, Q2W for 24 weeks (a 
total of 12 doses). 
 
 
 
 
 
 
 
Duration of Treatment 
All subjects will be treated with ND-L02-s0201 or placebo for 24 weeks (a total of 12 doses).  
Subject’s participation in the study will be approximately 40 weeks including a Screening and 
Baseline period of up to 6 weeks, a treatment period of 24 weeks (including the 2 weeks after the last 
study treatment), and a follow-up period of 10 weeks after End-of-Treatment (EOT). The end of trial 
will be the last subject, last visit (LSLV). 
Reference Therapy, Dosage, and Mode of Administration 
The reference therapy (placebo) is Sodium Chloride 0.9% for Injection (USP/EP/JP or equivalent). 
Reference therapy will be administered IV every 2 weeks for 24 weeks following the same 
procedures described for the IP. 
Assessments and Measurements 
Safety: 
To ensure safety of the overall study an independent Data Monitoring Committee (DMC) will be 
established. The DMC will periodically review the available safety and tolerability of study treatment 
for the duration of the study (see Section 7.4).  
The following safety assessments will be performed: 
• 
Adverse events: 
 
 
  
• 
Safety laboratory findings: 
 
 
 
 
 


Clinical Protocol: Study ND-L02-s0201-005 
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• 
Physical examinations, vital signs, and weight 
• 
12-Lead electrocardiograms (ECG) 
 
 
 
 
 
 
 
 
• 
Concomitant medications 
Biological Activity: 
• 
Pulse oximetry (peripheral capillary oxygen saturation [SpO2]) 
• 
FVC 
• 
DLCO (corrected for hemoglobin) 
• 
HRCT 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Endpoints 
Safety: 
• 
Incidence of treatment-emergent AEs (TEAEs) and treatment-emergent SAEs 
• 
Proportion of subjects discontinuing study treatment due to TEAEs  
Biological Activity: 
• 
Rate of decline in FVC over 24 weeks (measured in mL and % of predicted over unit time) 
• 
Absolute and relative change in FVC (mL and % of predicted) at Visit 14 (Day 169) as 
compared with baseline 


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• 
Proportion of subjects with an FVC response (mL and % of predicted) defined as either 
having improvement or a decline by 0 to ≤ 5%, > 5% to ≤ 10%, and > 10% at Visit 14 
(Day 169) 
• 
Change in DLCO and DLCO corrected for hemoglobin 
• 
Changes of ILA as measured by HRCT (ie, change in parenchymal feature [Baseline to 
Visit 14 (Day 169)]), as determined by qualitative assessment (central radiologist) and 
quantitative analysis (Quantitative Lung Fibrosis – QLF analysis) 
• 
Time to first acute IPF exacerbation (ie, an unexplained worsening of dyspnea, evidence of 
hypoxemia as defined by worsened or severely impaired gas exchange, new radiographic 
alveolar infiltrates, and an absence of an alternative explanation such as infection, pulmonary 
embolism, pneumothorax, or heart failure [Raghu et al, 2011]) 
• 
Rate of hospitalization for respiratory ailments, rate of mortality due to all causes, and rate of 
deterioration of IPF resulting in lung transplantation (up to 12 weeks after the end of study 
treatment) or death 
Pharmacokinetics: 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
Statistical Methods 
Populations of Interest: 
Safety Population: The safety population will include all subjects who receive at least 1 dose of study 
treatment. 
ITT Population: The intent-to-treat (ITT) population will include any randomized subjects. 
PK Population 1: This PK population will include subjects in the PK subset who receive at least 
1 dose of study treatment and have a majority of scheduled PK samples drawn for serial PK 
measurements that allow for PK parameters to be generated. Subjects who do not complete the study 
treatment infusion (Visit 2) will be excluded from the PK analysis. 
PK Population 2: This PK population will include subjects who receive the majority of the study 
treatment doses and also have a majority of the planned trough samples collected that allow for a 
comparison of trough levels across dosing weeks. 
Per Protocol Population: This population will exclude nonevaluable subjects and subjects with major 
protocol deviations thought to impact the ability to assess the effect of study treatment. Exclusion of 
subjects from the Per Protocol (PP) set will be reviewed, documented, and approved before the study 
is unblinded to the study Sponsor. The criteria for excluding subjects from the PP population will be 
specified in the Statistical Analysis Plan (SAP). 


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Demographic and Baseline Characteristics: 
The safety population will be used for summary of demographic and baseline characteristics. 
Demographic and baseline laboratory results will be summarized overall and by treatment arm using 
descriptive statistics. Additionally, the proportion of subjects on SOC upon randomization for each 
treatment arm will be summarized.   
Safety: 
All safety analyses will be performed on the safety population. 
The analysis of safety, reported for each treatment arm, will be based on the frequency of AEs and 
their severity for all treated subjects. The safety variables, including AEs, SAEs, and AEs of interest 
(coded using the Medical Dictionary for Regulatory Activities [MedDRA]), clinical laboratory tests 
 physical examination, ECGs, and vital 
signs will be summarized or tabulated by treatment arm. Some of the variables will be tabulated by 
treatment arm and by visit. Incidence of AEs will be further tabulated by subjects on SOC within each 
treatment arm. 
The proportion of subjects discontinuing study treatment due to AEs will be tabulated by treatment 
arm.  
Biological Activity: 
All biological activity analyses will be performed on the ITT population. 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 


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Table 1: 
Schedule of Events 
 Screeninga 
Treatment Period 
EOT 
Follow-Up 
Visit 
1a 
1b 
2 
3 
4 
5, 7, 9, 11, 13 
(Simple tests) 
6, 8, 10, 12  
(Detailed tests) 
14 (or ET) 
15 
16 
Week 
-6 to -1 
0 
2 
4 
6, 10, 14, 18, 22 
8, 12, 16, 20 
24  
(2 wk postdose) 
28  
(4 wk post 
V14/ET) 
34  
(10 wk post 
V14/ET) 
Study Day 
-42 to -7 
1 
2 
15 
29 
43, 71, 99, 127, 155 57, 85, 113, 141 
169 
197 
239 
Allowable Window (days)b 
 
 
 
± 4 ± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
Study Procedure 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
Xc 
 
 
 
 
 
 
 
 
 
 
Eligibility  
X 
X 
X 
 
 
 
 
 
 
 
 
Demographics and baseline characteristics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Adverse events 
Xd 
X 
X 
Xe 
X 
X 
X 
X 
X 
X 
X 
IPF history and previous treatments 
X 
 
 
 
 
 
 
 
 
 
 
Prior medications  
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medications  
Xd 
X 
X 
Xe 
X 
X 
X 
X 
X 
X 
X 
Physical examination (complete) 
X 
 
 
 
 
 
 
 
X 
 
 
Physical examination (abbreviated)f 
 
X 
X 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
 
X 
 
 
12-lead ECG 
X 
X 
 
 
 
Xg 
 
 
X 
 
 
Vital signsh 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Pulse oximetry: SpO2h 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Chemistry 
X 
 
X 
 
X 
X 
 
X 
X 
 
X 
Hematology 
X 
Xn 
X 
 
 
X 
 
X 
X 
Xn 
X 
Urinalysis  
X 
 
 
 
 
 
 
 
X 
 
X 
Pregnancy test (urine) for WCBPo 
X 
 
X 
 
 
X 
 
X 
X 
X 
X 
Serology (HCV Ab, HBsAg, HIV 1/2) 
X 
 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 testr 
X 
 
 
 
 
 
 
 
 
 
 


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 Screeninga 
Treatment Period 
EOT 
Follow-Up 
Visit 
1a 
1b 
2 
3 
4 
5, 7, 9, 11, 13 
(Simple tests) 
6, 8, 10, 12  
(Detailed tests) 
14 (or ET) 
15 
16 
Week 
-6 to -1 
0 
2 
4 
6, 10, 14, 18, 22 
8, 12, 16, 20 
24  
(2 wk postdose) 
28  
(4 wk post 
V14/ET) 
34  
(10 wk post 
V14/ET) 
Study Day 
-42 to -7 
1 
2 
15 
29 
43, 71, 99, 127, 155 57, 85, 113, 141 
169 
197 
239 
Allowable Window (days)b 
 
 
 
± 4 ± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
Premedication (optional)w 
 
 
X 
 
X 
X 
X 
X 
 
 
 
Study treatment 
 
 
X 
 
X 
X 
X 
X 
 
 
 
Abbreviations: 
 COVID-19 = coronavirus disease; 
 ECG = electrocardiogram; EOT = end-
of-treatment; ET = Early Termination; 
 HBsAg = hepatitis B surface antigen; HCV Ab = hepatitis C virus antibody; HIV 1/2 = human 
immunodeficiency virus type 1 or 2; 
 ICF = informed consent form; IPF = idiopathic pulmonary fibrosis;
 
QC = quality 
control; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; 
 SOC = standard of 
care;
 V = Visit; WCBP = women of childbearing potential; 
 
Note: Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
a Screening begins with the first Visit 1a procedure (excluding signing the ICF) and may be shorter than 42 days. If possible, plan Visit 1b and schedule the 
 at the time of 
Visit 1a. To assure that an ineligible subject does not undergo an unnecessary 
ALL Visit 1a procedures MUST be completed before any Visit 1b procedures may be 
started.
 
 
b Subjects should be dosed on the study day listed in the Study Schedule (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13), ensuring a minimum of 7 days between each dose. 
Assessments not associated with study treatment infusion may be performed on days other than the dosing day for scheduling purposes, as long as they are performed before the 
infusion. 
c The ICF should be signed before Visit 1a to allow the site to instruct the subject to withhold bronchodilator use as required for the Visit 1a PFT (see Section 11.2.2) 
 
 
d Adverse event and concomitant medication collection will begin 24 hours before Visit 1a. 
e On Day 2, study personnel will call subjects not returning to the site to collect any AEs and concomitant medications that may have occurred after leaving the site on Day 1. 
f Other abbreviated physical examinations may be performed at the discretion of the Investigator on the basis of signs or symptoms. See Section 11.1.3 for more information. 


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g During Visit 4 (Day 29), ECGs will be performed once, within 30 minutes after the end of the study treatment infusion. 
h Vital signs and SpO2 will be measured at every study visit, except at Visit 2 (Days 2 and 3; subjects participating in the PK substudy will only have vital signs measured). On 
dosing days vital signs and SpO2 will be measured thrice: once before the study treatment infusion (if premedication is administered, vital signs should be measured after 
premedication), midinfusion ± 5 minutes 
 
 and within 15 minutes after the end of the study treatment infusion. The frequency of monitoring vital signs may be increased as warranted by 
clinical management. See Section 11.1.4 and Section 11.2.1 for more information.  
 
 
 
 
 
 
 
 
 
 
 
o A positive urine pregnancy test will be followed up with a serum pregnancy test. 
 
 
 
r Every effort should be made to test for SARS-CoV-2 virus or viral antigen at Visit 1a if testing is available. The test used should have regulatory approval for marketing and 
sample collection should be performed per the assay’s specifications. Depending on the site and its location, options for subject testing may vary. Refer to Section 8.3.3 for 
guidance on SARS-CoV-2 testing. 
 
 
 
 
 
 
 
 
 
 
 
w Subjects may be premedicated to mitigate the risk of infusion-related reactions at the discretion of the Investigator (see Section 18.5). 


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3. 
TABLE OF CONTENTS AND LIST OF TABLES 
TABLE OF CONTENTS 
1. 
SIGNATURE PAGE ....................................................................................................2 
1.1. 
Sponsor Approval .........................................................................................................2 
1.2. 
Investigator Agreement ................................................................................................3 
2. 
SYNOPSIS ...................................................................................................................4 
3. 
TABLE OF CONTENTS AND LIST OF TABLES ..................................................17 
TABLE OF CONTENTS ...............................................................................................................17 
LIST OF TABLES .........................................................................................................................24 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................25 
5. 
INTRODUCTION ......................................................................................................30 
5.1. 
Idiopathic Pulmonary Fibrosis ....................................................................................30 
5.2. 
ND-L02-s0201 for Injection .......................................................................................30 
5.3. 
Study ND-L02-s0201-005 ..........................................................................................31 
5.4. 
Nonclinical Program ...................................................................................................31 
5.5. 
Clinical Program .........................................................................................................31 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. 
STUDY OBJECTIVES ..............................................................................................36 
6.1. 
Primary Objective .......................................................................................................36 
6.2. 
Secondary Objectives .................................................................................................36 
7. 
INVESTIGATIONAL PLAN .....................................................................................37 
7.1. 
Study Design ...............................................................................................................37 
7.2. 
Randomization ............................................................................................................37 
7.3. 
Blinding ......................................................................................................................38 


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7.4. 
Data Monitoring Committee .......................................................................................38 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................39 
8.1. 
Inclusion Criteria ........................................................................................................39 
8.2. 
Exclusion Criteria .......................................................................................................40 
8.3. 
Screening and Rescreening Procedures ......................................................................42 
8.3.1. 
Pulmonary Function Testing.......................................................................................42 
8.3.1.1. 
Screening ....................................................................................................................42 
8.3.1.2. 
Rescreening .................................................................................................................43 
8.3.2. 
Other Eligibility Criteria Assessments .......................................................................43 
8.3.3. 
COVID-19 Considerations .........................................................................................43 
8.3.3.1. 
Screening ....................................................................................................................43 
8.3.3.2. 
Rescreening .................................................................................................................43 
8.3.4. 
High-Resolution Computed Tomography Scanning ..................................................44 
8.3.4.1. 
Screening ....................................................................................................................44 
 
 
8.4. 
Subject Withdrawal ....................................................................................................44 
8.4.1. 
Withdrawal Criteria ....................................................................................................44 
8.4.2. 
Withdrawal Procedures ...............................................................................................45 
8.4.3. 
Documentation of Withdrawal ...................................................................................45 
8.4.4. 
Replacement of Subjects .............................................................................................45 
8.4.5. 
Stopping Rules ............................................................................................................45 
 
 
8.4.5.2. 
Subjects with Abnormal Baseline Values ...................................................................46 
8.5. 
Study Termination ......................................................................................................46 
9. 
INVESTIGATIONAL PRODUCT ............................................................................47 
9.1. 
Identity of Investigational Product .............................................................................47 
 
 
9.3. 
Storage of Clinical Supplies .......................................................................................47 
9.4. 
Drug Accountability ...................................................................................................48 
9.5. 
Return of Investigational Product ...............................................................................48 
9.6. 
Investigational Product Disposal at Study Center ......................................................48 
10. 
TREATMENT OF SUBJECTS ..................................................................................49 
10.1. 
Dosing Regimen .........................................................................................................49 


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10.2.2.1. 
ND-L02-s0201 for Injection or Placebo .....................................................................49 
10.2.2.2. 
Nintedanib ...................................................................................................................50 
10.2.2.3. 
Pirfenidone ..................................................................................................................50 
10.2.3. 
Dose Interruption ........................................................................................................50 
10.3. 
Prior and Concomitant Medications ...........................................................................50 
10.3.1. 
Prior Medications ........................................................................................................50 
10.3.2. 
Concomitant Medications ...........................................................................................50 
10.3.2.1. 
Premedication .............................................................................................................50 
10.3.2.2. 
Pirfenidone or Nintedanib ...........................................................................................50 
10.3.2.3. 
Contraceptives ............................................................................................................51 
10.3.2.4. 
Insulin .........................................................................................................................51 
10.3.2.5. 
Other ...........................................................................................................................52 
10.3.3. 
Prohibited Medications ...............................................................................................52 
10.4. 
Subject Compliance ....................................................................................................52 
11. 
BIOLOGICAL ACTIVITY, SAFETY, PHARMACOKINETIC, AND 
PHARMACODYNAMIC ASSESSMENTS ..............................................................54 
11.1. 
Safety ..........................................................................................................................54 
11.1.1. 
Adverse Events ...........................................................................................................54 
11.1.2. 
Safety Laboratory Tests ..............................................................................................54 
11.1.3. 
Physical Examinations ................................................................................................55 
11.1.4. 
Vital Signs ..................................................................................................................55 
11.1.5. 
12-Lead Electrocardiograms .......................................................................................56 
 
 
 
 
 
 
 
 
 
 
11.1.11. 
Concomitant Medications ...........................................................................................57 
11.2. 
Biological Activity ......................................................................................................57 
11.2.1. 
Pulse Oximetry ...........................................................................................................57 


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11.2.2. 
Pulmonary Function Testing.......................................................................................58 
11.2.2.1. 
General Guidelines .....................................................................................................58 
11.2.2.2. 
Timing .........................................................................................................................58 
11.2.2.3. 
Quality Control ...........................................................................................................59 
11.2.3. 
High-Resolution Computed Tomography Scanning ..................................................60 
11.2.3.1. 
Timing .........................................................................................................................60 
11.2.3.2. 
Guidelines ...................................................................................................................60 
 
 
11.2.5. 
Diagnosis of Idiopathic Pulmonary Fibrosis ..............................................................61 
 
 
 
 
11.3. 
Pharmacokinetics ........................................................................................................62 
 
 
 
 
11.4. 
Pharmacodynamics .....................................................................................................64 
 
 
 
 
12. 
STUDY PROCEDURES ............................................................................................65 
12.1. 
Screening ....................................................................................................................65 
12.1.1. 
Visit 1a ........................................................................................................................65 
12.1.2. 
Visit 1b........................................................................................................................66 
12.2. 
Treatment Period (Days 1 [Baseline] to 168) .............................................................67 
12.2.1. 
Visit 2 (Days 1 to 2) ....................................................................................................67 
12.2.1.1. 
Day 1 ...........................................................................................................................67 
12.2.1.2. 
Day 2 ...........................................................................................................................68 
12.2.2. 
Visit 3 (Day 15) All Subjects ......................................................................................68 
12.2.3. 
Visit 4 (Day 29) All Subjects ......................................................................................69 
12.2.4. 
Visits 5, 7, 9, 11, and 13 (Days 43, 71, 99, 127, 155) All Subjects ............................70 
12.2.5. 
Visits 6, 8, 10, and 12 (Days 57, 85, 113, and 141) All Subjects ...............................71 
12.3. 
End-of-Treatment (Visit 14 [Day 169]/Early Termination) .......................................72 
12.4. 
Follow Up ...................................................................................................................73 
12.4.1. 
Follow-Up Visit 1 (Visit 15/Day 197) ........................................................................73 
12.4.2. 
Follow-Up Visit 2 (Visit 16/Day 239) ........................................................................73 


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13. 
STATISTICS ..............................................................................................................75 
13.1. 
Study Endpoints ..........................................................................................................75 
13.1.1. 
Primary Endpoint ........................................................................................................75 
13.1.1.1. 
Safety ..........................................................................................................................75 
13.1.2. 
Secondary Endpoint ....................................................................................................75 
13.1.2.1. 
Biological Activity ......................................................................................................75 
 
 
 
 
13.2. 
Statistical Plan ............................................................................................................76 
13.2.1. 
Populations of Interest ................................................................................................76 
13.2.2. 
Demographic and Baseline Characteristics ................................................................76 
13.2.3. 
Safety ..........................................................................................................................77 
13.2.4. 
Biological Activity ......................................................................................................77 
 
 
 
 
13.3. 
Determination of Sample Size ....................................................................................79 
13.4. 
Deviation from Original Analysis Plan ......................................................................79 
14. 
ADVERSE EVENTS..................................................................................................80 
14.1. 
Adverse Event Definitions ..........................................................................................80 
14.1.1. 
Adverse Event .............................................................................................................80 
14.1.2. 
Suspected Adverse Reaction .......................................................................................80 
14.1.3. 
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse 
Reaction ......................................................................................................................80 
14.1.4. 
Serious Adverse Event or Serious Suspected Adverse Reaction ................................80 
14.1.5. 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction .................81 
14.2. 
Adverse Event Classification ......................................................................................81 
14.2.1. 
Treatment-Emergent Adverse Events .........................................................................81 
 
 
 
 
14.2.4. 
Respiratory Adverse Events .......................................................................................81 
14.2.5. 
Acute Exacerbation of IPF..........................................................................................82 
 
 
14.2.7. 
Relationship to Study Treatment, Premedication, and Standard of Care ...................82 


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14.2.8. 
Severity .......................................................................................................................83 
14.3. 
Exposure in Utero .......................................................................................................84 
14.4. 
Monitoring of Adverse Event Data .............................................................................84 
14.5. 
Documentation of Adverse Events by Investigator ....................................................84 
14.6. 
Notification about Serious Adverse Events and Serious and Unexpected 
Suspected Adverse Reactions .....................................................................................85 
14.6.1. 
Investigator Reporting to Sponsor ..............................................................................85 
14.6.2. 
Reporting to Regulatory Agencies and Institutional Review 
Boards/Independent Ethics Committees .....................................................................85 
14.7. 
Emergency Identification of Study Medication ..........................................................86 
14.8. 
Emergency Sponsor Contact .......................................................................................86 
15. 
ETHICS ......................................................................................................................87 
15.1. 
Institutional Review Board or Independent Ethics Committee ..................................87 
15.2. 
Ethical Conduct of the Study ......................................................................................87 
15.3. 
Subject Information and Informed Consent ...............................................................87 
16. 
STUDY ADMINISTRATION ...................................................................................88 
16.1. 
Administrative Structure .............................................................................................88 
16.2. 
Quality Control and Quality Assurance ......................................................................88 
16.2.1. 
Overview .....................................................................................................................88 
16.2.2. 
Risk Management .......................................................................................................88 
16.2.3. 
Monitoring ..................................................................................................................88 
16.2.4. 
Data Management/Coding ..........................................................................................89 
16.2.5. 
Quality Assurance Audit .............................................................................................89 
16.3. 
Data Handling and Recordkeeping .............................................................................89 
16.3.1. 
Electronic Data ...........................................................................................................89 
16.3.2. 
Case Report Form Completion ...................................................................................90 
16.3.3. 
Data Handling .............................................................................................................90 
16.3.4. 
Retention of Study Records ........................................................................................90 
16.4. 
Financing and Insurance .............................................................................................90 
16.5. 
Confidentiality ............................................................................................................90 
16.6. 
Publication Policy .......................................................................................................91 
16.7. 
Direct Access to Source Data .....................................................................................91 
16.8. 
Protocol Amendments ................................................................................................91 


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18. 
APPENDICES ............................................................................................................94 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
18.5. 
Appendix E: Premedication ......................................................................................106 
18.5.1. 
Premedications ..........................................................................................................106 
 
 
18.5.3. 
Documentation ..........................................................................................................107 
18.6. 
Appendix F: Restrictions Relating to COVID-19 ....................................................108 
18.6.1. 
Restrictions to Study Conduct ..................................................................................108 
18.6.2. 
Study Visit Guidelines ..............................................................................................108 
18.6.2.1. 
Consenting and Screening ........................................................................................108 
18.6.2.2. 
Managing Treatment Period Study Visits.................................................................109 
18.6.2.3. 
Managing End-of-Treatment and Follow-Up Period Visits .....................................109 
18.6.2.4. 
Data Collection During Remote Visits .....................................................................109 
 
 
18.6.3. 
Analysis Related to COVID-19 ................................................................................110 
18.6.4. 
Clinical Study Report ...............................................................................................110 


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LIST OF TABLES 
Table 1: 
Schedule of Events .....................................................................................................13 
 
 
Table 3: 
Abbreviations and Specialist Terms ...........................................................................25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 3: 
Abbreviations and Specialist Terms 
Abbreviation or 
Specialist Term 
Definition 
 
 
 
 
AE 
adverse event 
ALAT 
Latin American Thoracic Association 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
ATS 
American Thoracic Society 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI 
body mass index 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
 
 
 
 
COVID-19 
coronavirus disease 
CRA 
clinical research associate 
CRO 
contract research organization 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTL 
clinical trial lead 


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Abbreviation or 
Specialist Term 
Definition 
 
 
DLCO 
diffusion capacity of the lung for carbon monoxide 
DMC 
Data Monitoring Committee 
 
 
 
 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, fifth edition 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOT 
End-of-Treatment 
EP 
European Pharmacopeia 
ERS 
European Respiratory Society 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume in 1 second 
FU 
follow up 
FVC 
forced vital capacity 
 
 
GCP 
Good Clinical Practice 
 
 
GLI 
Global Lung Initiative 
HBsAg 
hepatitis B surface antigen 
HCV Ab 
hepatitis C virus antibody 
 
 
 
 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 1/2 
human immunodeficiency virus type 1 or 2 
 
 
 
 
HRCT 
high-resolution computed tomography 
HSP47 
heat shock protein 47 
ICF 
informed consent form 


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Abbreviation or 
Specialist Term 
Definition 
ICH 
International Council for Harmonisation  
IEC 
Independent Ethics Committee 
ILA 
interstitial lung abnormalities 
IND 
Investigational New Drug 
IP 
investigational product 
IPF 
idiopathic pulmonary fibrosis 
IRB 
Institutional Review Board 
ITT 
intent-to-treat 
IV 
intravenous 
IWRS 
interactive web response system 
JRS 
Japanese Respiratory Society 
JP 
Japanese Pharmacopeia 
 
 
 
 
LNP 
lipid nanoparticle 
LSLV 
last subject, last visit 
MDD 
multidisciplinary discussion 
MedDRA 
Medical Dictionary for Regulatory Activities  
NCA 
noncompartmental analysis 
NCI 
National Cancer Institute 
 
 
PD 
pharmacodynamic 
PEF 
peak expiratory flow 
 
 
PFT 
pulmonary function testing 
PI 
Principal Investigator 
 
 
PK 
pharmacokinetic(s) 
PP 
per protocol 
 
 
Q2W 
every 2 weeks 


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Abbreviation or 
Specialist Term 
Definition 
 
 
QA 
quality assurance 
QC 
quality control 
QLF 
Quantitative Lung Fibrosis 
 
 
QTcF 
QT interval corrected using Fridericia’s formula 
RNAi 
ribonucleic acid interference 
 
 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SD 
standard deviation 
 
 
siRNA 
small interfering ribonucleic acid 
SLB 
surgical lung biopsy 
SOC 
standard of care 
SOP 
standard operating procedure 
SpO2 
peripheral capillary oxygen saturation 
 
 
 
 
TEAE 
treatment-emergent adverse event 
 
 
 
 
TMF 
Trial Master File 
UIP 
usual interstitial pneumonia 
ULN 
upper limit of normal 
USP 
United States Pharmacopeia 
UV 
ultraviolet 
 
 
 
 
WBC 
white blood cell 


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Abbreviation or 
Specialist Term 
Definition 
WCBP 
women of childbearing potential 
WHODDE 
World Health Organization Drug Dictionary Enhanced  
 
 


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5. 
INTRODUCTION 
ND-L02-s0201 for Injection is being developed for idiopathic pulmonary fibrosis (IPF) by Nitto 
Denko Corporation (Nitto). ND-L02-s0201 for Injection is a lipid nanoparticle (LNP) 
formulation 
 
 
 
 
5.1. 
Idiopathic Pulmonary Fibrosis 
Idiopathic pulmonary fibrosis is a specific form of chronic, progressive fibrosing interstitial 
pneumonia of unknown cause. It occurs primarily in older adults and is limited to the lungs. 
Idiopathic pulmonary fibrosis is characterized by progressive worsening of dyspnea and lung 
function and is associated with a poor prognosis (Raghu et al, 2011). The median survival of 
patients with IPF is generally 2.5 to 3.5 years (Ley et al, 2011). Respiratory failure resulting from 
disease progression is the most frequent cause of death (Ley et al, 2011). 
Pulmonary fibrosis was initially thought to be the result of chronic inflammation, but current 
evidence indicates it is the result of an epithelial-driven and fibroblast-activated process in which 
inflammation may have an ancillary role (Selman et al, 2001). Type II pneumocytes and 
myofibroblasts in usual interstitial pneumonia (UIP) overexpress and co-express HSP47 and type 
I procollagen. Studies have demonstrated expression of human HSP47 is increased in fibrotic 
lesions of IPF, idiopathic nonspecific interstitial pneumonia, and diffuse alveolar damage 
(Razzaque et al, 1998; Kakugawa et al, 2005) and HSP47 is detected in the serum of patients 
with acute exacerbated IPF (Kakugawa et al, 2013). Myofibroblasts, through the production of 
HSP47-associated regulation of type I procollagen, likely play an important role in the 
progression of pulmonary fibrosis (Iwashita et al, 2000). 
5.2. 
ND-L02-s0201 for Injection 
ND-L02-s0201 for Injection is an LNP formulation 
 
 
 
 
 
 
 
 
 
 
  


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5.3. 
Study ND-L02-s0201-005 
This Phase 2 clinical study will be a randomized, double-blind, placebo-controlled, multicenter 
study to evaluate the safety, tolerability, biological activity, and pharmacokinetics (PK) of 
ND-L02-s0201 for Injection in subjects with IPF. Approximately 120 subjects will be enrolled 
(approximately 40 subjects in each of 3 arms). Subjects will be randomized 1:1:1 to a low dose 
of ND-L02-s0201 (45 mg), a high dose of ND-L02-s0201 (90 mg), or placebo. Subjects will 
receive study treatment every 2 weeks (Q2W) for 24 weeks and will be followed until 12 weeks 
after the last dose. 
This trial will be conducted in compliance with the protocol, Good Clinical Practice (GCP), and 
the applicable regulatory requirement(s). 
5.4. 
Nonclinical Program 
Refer to the Investigator Brochure for a summary of the nonclinical information available for 
ND-L02-s0201.  
5.5. 
Clinical Program 
Refer to the Investigator Brochure for a summary of the clinical information available for 
ND-L02-s0201.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6. 
STUDY OBJECTIVES 
6.1. 
Primary Objective 
• Evaluate the safety and tolerability of ND-L02-s0201, administered at 2 dose levels, 
Q2W over 24 weeks, versus placebo, in conjunction with standard of care (SOC) 
6.2. 
Secondary Objectives 
• Evaluate the biological activity of ND-L02-s0201 as measured by spirometry over 
24 weeks 
• Evaluate changes of interstitial lung abnormalities (ILA) as measured by high-
resolution computed tomography (HRCT)  
• Evaluate single-dose PK endpoints over 24 weeks in a subset of subjects 
• Evaluate trough levels for accumulation over time and identify when steady state 
conditions are achieved 


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Study Design 
This is a Phase 2, double-blind, placebo-controlled, randomized, multicenter, international study 
of 2 doses of ND-L02-s0201 for Injection to evaluate safety, tolerability, biological activity, and 
PK in subjects with a diagnosis of IPF. 
There will be 3 treatment arms. Two dose levels of ND-L02-s0201 will be evaluated in 2 arms: a 
low dose (45 mg) and a high dose (90 mg). A third arm will be administered placebo. 
The study will consist of a Screening period lasting up to 42 days, a 24-week treatment period 
including an End-of-Treatment (EOT) visit 2 weeks after the final dose (Visit 14), and 2 follow-
up (FU) visits 4 and 10 weeks after Visit 14. During the treatment period ND-L02-s0201 for 
Injection will be administered by intravenous (IV) infusion Q2W (± 4 days for Visit 3 or 
± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 
12 doses. Subject participation will be up to 281 days (approximately 40 weeks). The end of trial 
will be the last subject, last visit (LSLV). 
 
 
 
 
 
 
 
  
7.2. 
Randomization 
Approximately 120 eligible subjects will be randomly assigned 1:1:1 to 1 of 3 treatment arms: 
low dose ND-L02-s0201 for Injection (45 mg), high dose ND-L02-s0201 for Injection (90 mg), 
and a placebo arm. The randomization schedule will be prepared by an unblinded statistician. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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7.3. 
Blinding 
Unblinded study personnel will prepare and administer the study treatment. The Investigator and 
other members of staff involved with the study will remain blinded to the study treatment 
randomization code until the final database is locked. 
 
 
 
7.4. 
Data Monitoring Committee 
To ensure safety of the overall study an independent Data Monitoring Committee (DMC) will be 
established. The DMC will periodically review the safety and tolerability of study treatment for 
the duration of the study. The DMC will include a chairperson and pulmonologist who are 
experienced in IPF; all members will be experienced with clinical trials and evaluating AEs, and 
will not otherwise participate in the study. The DMC will also include an independent 
statistician. 
The DMC will review all available AEs, safety laboratory data, declines in pulmonary function 
tests meeting thresholds defined in Section 11.2.2, 
 at 
preset times. The first scheduled meeting will occur after 25% of subjects have completed 
1 month of the study (ie, Visit 4, Day 29). The second scheduled meeting will occur after 50% of 
subjects have completed Visit 4 (Day 29). The third scheduled meeting will occur after 75% of 
subjects have completed Visit 8 (Day 85). All data listed for all subjects available at the time of 
the meeting will be included for review. 
Following review, the DMC will recommend continuation, modification, or discontinuation of 
the study based on observed toxicities. A DMC charter will describe the activities of this 
committee. 
In the event of unexpected AE or serious adverse event (SAE) findings or other critical safety-
related issues (eg, the coronavirus disease [COVID-19] pandemic), Nitto or the DMC may 
convene an ad hoc meeting. Such a meeting will outline the cause of concern and may identify a 
data cut-off as part of the scheduling request.  


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8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Inclusion Criteria 
To be randomized, all subjects must meet the criteria listed below.  
1. Males and females between 40 and 80 years of age, inclusive, at the time of consent. 
2. Diagnosis of IPF within 5 years before Visit 1a, confirmed by the Principal Investigator 
(PI) using American Thoracic Society (ATS)/European Respiratory Society 
(ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 
guidelines (Raghu et al, 2011 or Raghu et al, 2018; see Section 11.2.5).  
a. Clinical management of the patient at the site must be for IPF and the PI must be 
convinced that all locally available information support UIP/IPF is the most likely 
diagnosis. It is mandatory that the PI consider overreader interpretation of Visit 1b 
HRCT and, if performed, SLB in order to determine that a subject is eligible for this 
trial. 
3. Extent of fibrosis greater than emphysema on HRCT. 
4. If on pirfenidone or nintedanib, unchanged dose for at least 12 weeks before Visit 1a. 
Subjects may not be on both pirfenidone and nintedanib. 
5. Forced vital capacity (FVC) ≥ 45% of predicted.  
6. Diffusion capacity of the lung for carbon monoxide (DLCO) corrected for hemoglobin 
≥ 30% of predicted value. 
7. Pulse oximetry saturation ≥ 90%, at rest while breathing ambient air or ≤ 2 L/minute 
supplemental oxygen by nasal prongs/cannula (see Section 11.2.1).  
8. Ratio of forced expiratory volume in 1 second (FEV1) to FVC ≥ 0.70. 
9. Adequate liver and renal function, as demonstrated by: 
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless participant has a 
documented history of Gilbert’s syndrome 
• Aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 × ULN 
• Creatinine < 2 × ULN 
• Serum albumin > 3.5 g/dL 
10. Life expectancy of ≥ 12 months.  
 
12. Women of childbearing potential (WCBP) must be willing to use a highly effective 
method of contraception throughout the study and study follow up or for at least 90 days 
after the last dose of study treatment (refer to Section 10.3.2.3). 
13. Women must be willing not to breastfeed for 90 days after the last dose of the study 
treatment. 


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14. Males must agree to use a condom throughout the study and for 90 days after the last 
dose of study treatment to prevent seminal transmission of the investigational product 
(IP). 
15. Males with female partners of childbearing potential must agree to use a highly effective 
method of contraception (refer to Section 10.3.2.3) throughout the study and for 90 days 
after the last dose of study treatment. All men with female partners of childbearing 
potential will be instructed to contact the Investigator immediately if their partner 
becomes pregnant at any time during study participation. All men must agree not to 
donate semen throughout the study and for 90 days after the last dose of study treatment. 
16. Willing and able to provide written informed consent and comply with the study 
procedures and visit schedule, including follow-up visits. 
8.2. 
Exclusion Criteria 
Potential subjects who meet any of the following criteria at Screening will be excluded from the 
study: 
1. Best, acceptable FVC from separate Screening spirometry that differ by ≥ 200 mL. See 
Section 8.3.1 for more information. 
2. Respiratory exacerbation(s) or hospitalization for IPF exacerbation within 3 months 
before Visit 1a. 
3. Taking both pirfenidone and nintedanib concurrently within 12 weeks before Visit 1a. 
4. Anticipated to receive a lung transplant during the subject’s participation in the study. 
5. Diagnosis of any connective tissue disease with a natural history that may be associated 
with pulmonary disease. 
6. Clinical evidence of or known history of cirrhosis. 
 
 
8. Uncontrolled cardiac disease or cardiac surgical procedure (eg, New York Heart 
Association Class III or IV, myocardial infarction, transient ischemic attack, uncontrolled 
atrial or ventricular cardiac arrhythmias, unstable angina, stroke, coronary angioplasty, 
coronary artery bypass graft) within 30 days before Visit 1a. 
9. Active smoker or smoking cessation within 12 weeks before Visit 1a. 
10. Malignancy within the last 5 years, with the exception of curable cancer (eg, basal or 
squamous cell skin cancer, cervical cancer in situ, nonmedullary thyroid carcinoma) who 
has received adequate treatment (eg, excision). 
11. Evidence of any unstable or untreated, clinically significant disease or condition that, in 
the opinion of the Investigator, might confound the interpretation of the study or place the 
subject at increased risk (eg, uncontrolled hypertension, diabetes mellitus). Subjects will 
have to have been on stable treatment for at least 4 weeks before Visit 1a. 


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12. Treatment with high dose corticosteroids, cytotoxic agents (eg, chlorambucil, 
azathioprine, cyclophosphamide, methotrexate), unapproved IPF-targeted therapy, and 
cytokine modulating agents within 8 weeks or 5 half-lives (whichever is longer) before 
Visit 1a. 
• A dose of ≤ 15 mg/day prednisone, or equivalent, is acceptable if unchanged for 
≥ 10 weeks before Visit 1a and is expected to remain unchanged during the subject’s 
participation in the study.  
13. Receiving an investigational treatment, whether or not approved for marketing, with the 
last dose of that study drug within 8 weeks or 5 half-lives (whichever is longer) before 
Visit 1a. Individuals allocated to receive no treatment beyond SOC in an investigational 
study are not excluded from this trial. 
14. History of allergic reaction to any of the study drugs to be administered. 
15. Pregnant or breastfeeding. 
16. Veins unsuitable for repeated venipuncture or IV infusion (eg, veins that are difficult to 
locate, access, or puncture; veins with a tendency to rupture during or after puncture), in 
the opinion of study center personnel. 
17. Known history of human immunodeficiency virus (HIV) infection, active chronic 
hepatitis B (eg hepatitis B surface antigen positive), and/or untreated hepatitis C antigen 
positive patients (with or without abnormal liver enzymes). If treated for hepatitis C viral 
eradication, then a viral load below the limits of quantitative detection for at least 
12 weeks must be documented. 
18. History of alcohol abuse and/or dependence within the last 2 years, as determined by the 
Investigator. 
19. History within the last 2 years of significant mental illness, or dependence on any opioid 
or illicit drugs as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth 
Edition (DSM-5). 
20. Suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
infection, defined as meeting one or more of the following criteria: 
a. The subject has known exposure to a person with signs or symptoms of SARS-CoV-2 
infection or has tested positive for SARS-CoV-2 (suggesting current infection) within 
21 days prior to the subject’s Visit 1a. 
b. The subject has current signs and symptoms suggestive of SARS-CoV-2 infection. 
c. The subject has SARS-CoV-2 virus or viral antigen detected at Visit 1a using a test 
approved for marketing if testing is available. (Detection of antibody to SARS-CoV-2 
will not be exclusionary. Refer to Section 8.3.3.1 for more guidance on SARS-CoV-2 
testing.) 


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8.3. 
Screening and Rescreening Procedures 
8.3.1. 
Pulmonary Function Testing 
8.3.1.1. 
Screening 
Additional information regarding pulmonary function testing (PFT) is in Section 11.2.2. 
Pulmonary function testing will be performed at study visits on separate days during Screening. 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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8.3.2. 
Other Eligibility Criteria Assessments 
Subjects with a confirmed diagnosis of IPF per this protocol’s eligibility criteria who fail 
Screening may be rescreened once if there is a change in status that, in consideration of protocol 
criteria by the Investigator and Medical Monitor, would allow participation in the study. 
8.3.3. 
COVID-19 Considerations 
8.3.3.1. 
Screening 
Refer to exclusion criterion 20 for eligibility restrictions related to suspected or confirmed 
SARS-CoV-2 infection. 
In terms of exclusion criterion 20c, every effort should be made to test for SARS-CoV-2 virus or 
viral antigen at Visit 1a if testing is available. The test used should have regulatory approval for 
marketing and sample collection should be performed per the assay’s specifications. Depending 
on the site and its location, options for subject testing may vary. Therefore, any of the following 
testing options are acceptable and are listed in order of preference: 
• Local testing performed concurrent with Visit 1a. 
• If local testing is not possible, testing should be performed using the central 
laboratory (if this option is in place and available to the site). 
• If neither local nor central laboratory SARS-CoV-2 testing are available, exclusion 
criterion 20c may be omitted in subjects who do not meet either criterion 20a or 20b. 
In this case, it should be properly documented in eCRF. 
• Detection of antibody to SARS-CoV-2 is not exclusionary. 
If a subject has a positive result from any test to detect SARS-CoV-2 virus or viral antigen 
within 21 days prior to Visit 1a: 
• If this finding is identified before signing the informed consent, the subject should not 
be consented until asymptomatic > 21 days. 
• If the finding is identified after signing the consent, the subject should be considered 
a screen failure with the option to rescreen as detailed in Section 8.3.3.2. 
If local or central SARS-CoV-2 testing is performed, the result should be available and reviewed 
before Visit 1b HRCT is conducted, consistent with Section 12.1. If the SARS-CoV-2 test is 
positive, the Visit 1b HRCT will not be performed. 
8.3.3.2. 
Rescreening 
A subject who was ineligible due to exclusion criterion 20 or details in Section 8.3.3.1, may 
rescreen in the following situations: 


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• The subject has been asymptomatic > 21 days after exposure to a person as described 
in exclusion criterion 20a. 
• The subject’s signs and symptoms of SARS-CoV-2 infection have completely 
resolved > 21 days prior to the planned date of Rescreening. 
• The subject is asymptomatic for SARS-CoV-2 infection > 21 days after SARS-CoV-2 
virus or viral antigen was detected and prior to the planned date of Rescreening. 
8.3.4. 
High-Resolution Computed Tomography Scanning 
8.3.4.1. 
Screening 
An individual whose clinical management at the site is for IPF, may be consented for 
participation in this study, in the absence of obvious excluding criteria.  
 
 
 
 
 
 
 
8.4. 
Subject Withdrawal 
8.4.1. 
Withdrawal Criteria 
Subjects may choose to withdraw from study treatment or the study at any time for any reason. 
In addition, subjects must have study treatment discontinued for any of the following reasons:  
• The subject is unwilling or unable to adhere to the protocol. 
• The subject becomes pregnant or begins breastfeeding. 
• The subject experiences an SAE, clinically significant AE, severe laboratory 
abnormality, intercurrent illness, or other medical condition that indicates to the 
Investigator that continued participation is not in the best interest of the subject. 
• 
 
 


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• Another medical reason, at the discretion of the Investigator and/or the Medical 
Monitor that indicates continued participation is not in the best interest of the subject.  
The only reason for withdrawal from the study should be subject withdrawal of consent to 
participate.
 
 
 Subjects who discontinue study treatment should be followed for 
outcomes as long as they agree to continued participation in the study. 
8.4.2. 
Withdrawal Procedures 
If it is necessary for a subject to discontinue study treatment before completion, the subject 
should complete all ET and follow-up procedures (refer to Section 12.3 and Section 12.4) if he or 
she is willing and it is not medically contraindicated. At a minimum, all safety-related 
procedures should be performed. Refer to Section 18.6 for guidance on clinical trial conduct 
relating to COVID-19. 
The Investigator must notify the Sponsor and/or the Medical Monitor within 24 hours when a 
subject has discontinued study treatment because of an AE. Any subject who discontinued study 
treatment because of a treatment-related AE (whether serious or nonserious), including clinically 
significant abnormal laboratory test results, will be evaluated by the Investigator or a designee 
and will be treated and/or monitored until resolution, stabilization, or until it has been determined 
that the study treatment or participation is not the cause. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. The Investigator or designee should inquire about the reason and will contact the subject 
by telephone as scheduled to collect AE information. 
If the subject discontinues study treatment and also withdraws consent for disclosure of future 
information, no further evaluations will be performed, and no additional data will be collected. 
The Sponsor may retain and continue to use data collected before consent was withdrawn. 
8.4.3. 
Documentation of Withdrawal 
The reason(s) for discontinuation of study treatment or withdrawal of consent must be recorded 
in the subject’s electronic case report form (eCRF). 
8.4.4. 
Replacement of Subjects 
Subjects who withdraw from the study will not be replaced. Subjects whose participation in the 
study was affected by restrictions relating to COVID-19 may be replaced if necessary to achieve 
this trial’s objectives. 
8.4.5. 
Stopping Rules 
Subjects will be monitored for evidence of drug-induced liver injury based on regulatory 
guidelines.  
 
 
 
 


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8.5. 
Study Termination 
Although the Sponsor has every intention of completing the study, the Sponsor reserves the right 
to discontinue the study at any time for clinical or administrative reasons or if required by the 
United States Food and Drug Administration (FDA) or other regulatory authorities. The Medical 
Monitor will review the safety of the study treatment regimen throughout the study. The study 
may be halted at any time for safety concerns. 


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9. 
INVESTIGATIONAL PRODUCT 
Only unblinded site staff will be responsible for the receipt, storage, accountability, preparation, 
administration, and disposition of all IP. Unblinded site staff must be made fully aware that they 
are not to disclose any unblinded information to any blinded individual including the subject, site 
staff, sponsor, and monitors. 
9.1. 
Identity of Investigational Product 
ND-L02-s0201 for Injection is an LNP formulation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.3. 
Storage of Clinical Supplies 
It is the responsibility of the Investigator to ensure that the IP is stored as specified by the 
Sponsor and in accordance with applicable regulatory requirements. The ND-L02-s0201 for 
Injection storage area must be secure with controlled access. Clinical supplies will be shipped to 
the study center pharmacy by the Sponsor or an approved vendor after the necessary regulatory 
documents have been received from the study center.  
 


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9.4. 
Drug Accountability 
It is the responsibility of the Investigator to maintain IP accountability at the clinical trial site and 
ensure that a current record of IP disposition is maintained at the study site. It is the 
responsibility of the Investigator to ensure that the IP is used only in accordance with the 
approved protocol. Records or logs must comply with applicable regulations and guidelines, and 
should include the following: 
• Amount received and placed in the storage area 
• Amount currently in the storage area 
• Lot number or batch number 
• Dates and initials of the person responsible for each IP inventory entry/movement 
• Amount dispensed to each subject, including unique subject identifiers 
• Amount transferred to another area for dispensing or storage 
• Nonstudy disposition (eg, lost, wasted, not used) 
• Amount returned to Sponsor or a designee, if applicable 
• Amount destroyed at the study center, if applicable 
The Sponsor or a designee will provide forms to facilitate inventory control if study center 
personnel do not have an established system that meets these requirements. 
9.5. 
Return of Investigational Product 
Refer to the study Pharmacy Manual for information regarding the return of IP.  
9.6. 
Investigational Product Disposal at Study Center 
Refer to the study Pharmacy Manual for information regarding IP disposal.  


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10. 
TREATMENT OF SUBJECTS 
10.1. 
Dosing Regimen 
ND-L02-s0201 for Injection will be administered at a dose of either 45 mg (low dose) or 90 mg 
(high dose). Study treatment (ND-L02-s0201 for Injection or placebo) will be dosed via IV 
infusion Q2W for 24 weeks as described in Table 1. Acceptable windows around dosing are 
± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each 
dose. Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
10.2. 
Preparation and Administration 
 
 
10.2.1. 
Dose Preparation 
 
 
  
 
 
 
 
 
 
10.2.2. 
Dose Administration 
10.2.2.1. ND-L02-s0201 for Injection or Placebo 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 


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10.2.2.2. Nintedanib 
Subjects who are taking nintedanib at the start of the study should be instructed to take 
nintedanib in accordance with the prescribing information. Dose adjustment or discontinuation of 
SOC in accordance with the prescribing information is permitted if clinically indicated (see 
OFEV® Package Insert, 2018). On days when ND-L02-s0201 for Injection is being administered, 
subjects should take the morning dose of nintedanib before the infusion. On days when overnight 
fasting is required for sample collection, subjects should take nintedanib with their first meal of 
the day as prescribed (ie, after blood samples are collected). 
10.2.2.3. Pirfenidone 
Subjects who are taking pirfenidone at the start of the study should be instructed to take 
pirfenidone in accordance with the prescribing information. Dose adjustment or discontinuation 
of SOC in accordance with the prescribing information is permitted if clinically indicated (see 
ESBRIET® Package Insert, 2017). On days when ND-L02-s0201 for Injection is being 
administered, subjects should take the first dose of pirfenidone before the infusion. On days 
when overnight fasting is required for sample collection, subjects should take pirfenidone with 
their first meal of the day as prescribed (ie, after blood samples are collected). 
10.2.3. 
Dose Interruption 
Any interruption or other change in the study treatment infusion must be documented (see 
Section 10.4).  
10.3. 
Prior and Concomitant Medications 
All medications taken within 14 days before Visit 1a through end of study should be recorded in 
the eCRF. 
10.3.1. 
Prior Medications 
Prior medications are those taken within 14 days before Visit 1a until 24 hours before Visit 1a, or 
a longer period as specified in the exclusion criteria (see Section 8.2).  
10.3.2. 
Concomitant Medications 
Concomitant medications are those taken beginning 24 hours before Visit 1a.  
10.3.2.1. Premedication 
Refer to Section 18.5 for more information. 
10.3.2.2. Pirfenidone or Nintedanib 
If the subject has been taking either pirfenidone or nintedanib at an unchanged dose for at least 
12 weeks before Visit 1a (Section 8.1), the same medication should be continued during the 
subject’s participation in this trial. The dose of the medication should remain the same during the 


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subject’s participation in the study. However, dose adjustment or discontinuation of SOC in 
accordance with the prescribing information is permitted if clinically indicated. 
If the subject is not taking either pirfenidone or nintedanib at Screening, neither medication may 
be taken through Week 24 (Visit 14) or ET. After the collection of data at Week 24 (Visit 14) 
subjects may begin taking either medication at the discretion of the study doctor. Subjects may 
not be taking both pirfenidone and nintedanib during the study.  
10.3.2.3. Contraceptives 
Female Subjects 
Female subjects of childbearing potential must use a highly effective method of contraception 
during participation in the study and study follow up or for 90 days after the last dose of study 
treatment.  
Methods of contraception considered highly effective include 1 of the 5 listed below: 
1. Hormonal contraception (eg, injection, implant, pill, patch, or vaginal ring as available in 
each country) associated with inhibition of ovulation (both estrogen and progestogen and 
progestogen only) in use for at least 30 days before administration of study treatment 
2. Intrauterine device in use for at least 30 days before administration of study treatment 
3. Intrauterine hormone-releasing system (IUS) in use for at least 30 days before 
administration of study treatment 
4. Bilateral tubal occlusion/ligation at least 6 months before administration of study 
treatment 
5. Partner who has been vasectomized at least 6 months before administration of study 
treatment 
Note: A woman is considered to be of nonchildbearing potential if she meets one of the 
following criteria: a) postmenopausal with at least 12 months of spontaneous amenorrhea; b) has 
had a bilateral oophorectomy; or c) has had a hysterectomy. 
Male Subjects  
All males must agree to use a condom throughout the study and for 90 days after the last dose of 
study treatment to prevent seminal transmission of the IP. 
In addition, males with female partners of childbearing potential must agree to use a highly 
effective method of contraception (see above) throughout the study and for 90 days after the last 
dose of study treatment. 
10.3.2.4. Insulin 
If the subject has diabetes, instruct them to adhere to the following recommendations to make 
sure that fasting is safe. 
If the subject does not take insulin for diabetes, instruct them to: 
• Not take any oral diabetes medications while fasting; 
• Drink 250 mL (around 8 oz) of plain water every 4-6 hours prior to blood sampling; 


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• Eat a meal or snack after blood sample(s) is/are collected; 
• Resume medications after eating the meal or snack. 
If the subject does take insulin for diabetes, instruct them to: 
• If on a basal injectable insulin dose (intermediate of long acting) the recommendation 
is to reduce normal insulin dose by one half or one third of the usual total morning 
dose depending on the fasting blood glucose in the morning after awakening; 
• Omit any short-acting (eg, regular) or rapid-acting (eg, lispro, aspart, glulisine) 
insulin prior to blood sampling; 
• If on continuous insulin infusion (insulin pump), the usual basal infusion rate does not 
need to be adjusted; 
• Drink 250 mL (around 8 oz) of plain water every 4-6 hours prior to blood sampling; 
• Eat a meal or snack after blood sample(s) is/are collected; 
• Resume short-acting (eg, regular) or rapid-acting (eg, lispro, aspart, glulisine) insulin 
after eating the meal or snack. 
10.3.2.5. Other 
After enrollment into the study, every attempt should be made to avoid changes in the subject’s 
medication regimen. Exceptions would include episodes of infections requiring treatment (eg, 
antibiotics or antiviral drugs), exacerbations of their underlying disease requiring immediate 
intervention, or any other situation requiring modification of the subject’s therapy for their safety 
at the discretion of the treating physician or the Investigator. 
10.3.3. 
Prohibited Medications 
Subjects should not be receiving high dose corticosteroids (ie, > 15 mg/day of prednisone or its 
equivalent), cytotoxic agents (eg, azathioprine, cyclophosphamide, methotrexate), unapproved 
IPF-targeted therapy, or cytokine modulating agents while participating in this study, nor can 
they have received such within 8 weeks or 5 half-lives (whichever is longer) before Visit 1a.  
Note: a dose of ≤ 15 mg/day prednisone, or equivalent, is acceptable if unchanged for 
≥ 10 weeks before Visit 1a and is expected to remain unchanged during the subject’s 
participation in the study.  
Note: a systemic dose of corticosteroid may be administered as premedication (see Section 18.5). 
 
 
10.4. 
Subject Compliance 
Study treatment will be administered at the study center by study center personnel.  
The time that each study treatment infusion began and ended, including the volume of study 
treatment administered and IV infusion rate will be recorded in source documents and eCRFs. 


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The infusion pump read-out should be used to record the volume of study treatment 
administered.  
Any interruption or other change in the study treatment infusion must be documented. More 
specifically, the time the infusion was interrupted, the time the infusion was resumed, the total 
duration of the interruption, and the time that any rate change began or ended must be 
documented in actual time.  


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11. 
BIOLOGICAL ACTIVITY, SAFETY, PHARMACOKINETIC, 
AND PHARMACODYNAMIC ASSESSMENTS 
To prevent missing data, if a subject does not return for a scheduled visit, every effort should be 
made, as per the site’s standard practice, to contact the subject to determine if any steps can be 
taken to facilitate compliance to study visits. 
 
  
11.1. 
Safety 
11.1.1. 
Adverse Events 
Adverse events will be evaluated for incidence, severity, and relationship to study treatment. 
 
 
  
Refer to Section 14 for AE definitions, classifications, and reporting requirements. 
 
 
 
  
11.1.2. 
Safety Laboratory Tests 
Safety laboratory tests will include the following: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Central laboratories will be used for clinical laboratory tests, although local testing may be used 
for emergencies and for hemoglobin for DLCO correction. Details regarding specimen collection 
and processing will be provided in the Lab Manual. Safety laboratory tests will be analyzed 
throughout the study. 


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Blood samples and urine samples will be collected for clinical laboratory testing as shown in 
Table 1. If needed, additional blood samples may be taken for DLCO correction. See 
Section 8.4.5 for guidance on how to manage subjects with elevations in transaminases. 
11.1.3. 
Physical Examinations 
Physical examinations will be conducted by the Investigator or qualified designee. A complete 
physical examination will include the following body systems: general appearance, 
eyes/ears/nose/throat/head/neck, chest and lungs (including inspection of the thorax for scars 
consistent with surgical lung biopsy at Screening), cardiovascular, abdomen, musculoskeletal, 
lymphatic, dermatologic, neurologic, psychiatric, and extremities. A complete physical 
examination, including recording of weight, will be conducted as shown in Table 1.  
An abbreviated physical exam includes general appearance, nose/throat, jugular venous 
distension (sitting; absent or present), auscultation of the lungs (anterior/posterior, 4 quadrants; 
wheezes, crackles, rhonchi [absent or present], other sounds [describe]), auscultation of the heart, 
lower extremity venous distention (absent or present), pitting edema (0, 1+, 2+, 3+, or 4+). An 
abbreviated physical examination will be performed as shown in Table 1. Other abbreviated 
physical examinations may be performed at the discretion of the Investigator on the basis of 
signs or symptoms.
 
 
Height (not a safety assessment) will be recorded only at Visit 1a. 
11.1.4. 
Vital Signs 
Vital signs will include systolic and diastolic blood pressure, heart rate, respiration rate, and oral 
temperature and will be measured at every study visit as shown in Table 1. All measurements 
should be performed in the semisupine or sitting position after the subject has rested in that 
position for at least 5 minutes. When feasible, vital signs should be performed in the same 
position at each visit. Blood pressure may be obtained with an automated or manual blood 
pressure apparatus; however, the same method should be used for any given subject throughout 
the study. Blood pressure and heart rate should be measured in the arm opposite that used for 
infusion of study treatment, and the arm used should be documented. 
Vital signs will be measured according to the following schedule:  
• Once before the study treatment infusion (if premedication is administered, vital signs 
should be measured after premedication) 
• midinfusion ± 5 minutes (if infusion is administered at a modified rate due to an 
infusion-related reaction, the timing should correspond to the middle of the modified 
infusion duration) 
• Within 15 minutes after the end of the study treatment infusion 
The frequency of monitoring vital signs may be increased as warranted by clinical management. 
If an AE occurs during the study treatment infusion, vital signs will be measured within 
5 minutes of the start of the AE and repeated at a minimum frequency of every 15 minutes until 
its resolution. 
 
 


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11.1.5. 
12-Lead Electrocardiograms 
Standard single 12-lead electrocardiograms (ECGs) will be performed after subjects have been 
resting for 5 minutes. If possible, the same model of ECG machine using the same algorithms 
should be used for any given subject for all assessments throughout the study. Heart rate as well 
as RR, PR, QRS, QT, and QTcF (QT interval corrected using Fridericia’s formula) intervals will 
be recorded in the eCRF. The Investigator should recalculate intervals and over read the machine 
interpretation, as necessary. A global interpretation of the ECG will be recorded as to whether 
the ECG is within normal limits or abnormal with any clinically significant findings noted.  
Standard 12-lead ECGs will be performed as shown in Table 1. During Visit 4, ECGs will be 
performed once, within 30 minutes after the end of the study treatment infusion. Additional 
ECGs may be performed if clinically indicated. 
Clinically significant changes not already noted or significantly worsened than documented in 
Medical History will be recorded as AEs. 
 
  
 
 
 
 
 
 
 
 
  
 
  
 
 
  
 
 
 
 
 
 
 
 


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11.1.11. 
Concomitant Medications 
At each study visit after signing the informed consent through to the FU visit, subjects will be 
asked about medications taken. 
11.2. 
Biological Activity 
11.2.1. 
Pulse Oximetry 
Pulse oximetry (SpO2) will be performed with vital signs as shown in Table 1. 
 
 
 
 
 
 
 
 
All documentation must include whether SpO2 was measured with the subject breathing ambient 
air or supplemental oxygen; if on supplemental oxygen, the flow and means of administration 
must also be recorded. When feasible, SpO2 measurements will be performed with the subject in 
the same position at each visit.  
SpO2 will be measured (with vital signs) according to the following schedule:  
• Once before the study treatment infusion (if premedication is administered, vital signs 
should be measured after premedication) 
• midinfusion ± 5 minutes (if infusion is administered at a modified rate due to an 
infusion-related reaction, the timing should correspond to the middle of the modified 
infusion duration) 
• Within 15 minutes after the end of the study treatment infusion 


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The frequency of monitoring may be increased as warranted by clinical management. If an AE 
occurs during the study treatment infusion, SpO2 will be measured within 5 minutes of the start 
of the AE and repeated at a minimum frequency of every 15 minutes until its resolution. 
 
 
 
 
11.2.2. 
Pulmonary Function Testing 
11.2.2.1. General Guidelines 
Pulmonary function testing will include both DLCO and spirometry. 
Pulmonary function testing (PFT) for this trial will be conducted in accordance with the PFT 
Manual that will be provided by the central PFT vendor for these services. The manual will 
include information on equipment and subject test instructions. 
 
 
 
 
 
 
PFT may only be performed on subjects in this trial by site personnel who have been determined 
by the PFT vendor to meet certification criteria. Whenever possible, all PFTs on a single subject 
should be performed: 
• on the same equipment 
• by the same site personnel 
• under the same conditions 
The Global Lung Initiative (GLI) 2012 spirometry reference values (Quanjer et al, 2012) and the 
GLI 2017 DLCO (TLCO) reference values (Stanojevic et al, 2017) will be used for all PFTs.  
11.2.2.2. Timing 
 
 
 
Timing of PFT and Bronchodilators 
All PFT on a single subject should be performed at the same time of day (± 2 hours). All PFT for 
this trial should be performed after withholding prescribed bronchodilators, either beta-agonists 
or anticholinergic agents, as follows: 
• short acting agents, typically prescribed on an as needed basis, withheld 4 hours 
before the study visit 
• twice daily agents, withheld 12 hours before the study visit 
• once daily agents, withheld 24 hours before the study visit 


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Note that inhaled corticosteroids are not bronchodilators and may continue to be taken prior to 
PFT without a change in schedule. 
All PFT will only be performed prebronchodilator; there will be no postbronchodilator testing. 
The requirement to withhold prescribed bronchodilators prior to PFT is especially important 
before the first Screening PFT (Visit 1a). If a subject is taking prescribed bronchodilators, then 
the first Screening PFT may not be performed on the day that informed consent is obtained; it is 
not acceptable to alter the SOC to accommodate research specifications until after informed 
consent has been obtained. After informed consent has been obtained, subjects should be 
provided a reminder to withhold prescribed bronchodilators before each subsequent study visit 
when PFT will be performed. If a subject should present for PFT on any occasion other than the 
first Screening visit having forgotten to withhold prescribed bronchodilators for the specified 
time(s), PFT should be delayed as long as possible but still performed at that visit and within the 
window specified above; an appropriate notation must be captured in source records and the 
corresponding eCRF. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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 In the event the repeat PFT is 
scheduled when the subject’s status has continued to deteriorate and either the subject or the 
Investigator determines testing is not feasible: 
• a notation that PFT was “not possible” should be entered into the corresponding 
eCRF and the most recent PFT results will be used for statistical analysis 
• a notation that PFT was “not possible” should be recorded in source records 
11.2.3. 
High-Resolution Computed Tomography Scanning 
11.2.3.1. Timing 
 
 
11.2.3.2. Guidelines 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Detailed specifications will be provided in the HRCT Manual. At a minimum, all HRCT scans 
should:  
• be performed only on scanners that have been “certified”, including phantom 
imaging, as specified in the HRCT Manual 
• all be performed on the same scanner for an individual subject, unless not feasible 
due to technical issues 
• be performed by the same technician for an individual subject whenever possible 
• be performed in the absence of radiopaque contrast 
• have subjects in the same position(s) as specified in the HRCT Manual 
• at full inhalation without (respiratory) motion 
• employ scanner settings and reconstruction algorithm(s) as specified in the HRCT 
Manual 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.2.5. 
Diagnosis of Idiopathic Pulmonary Fibrosis 
The diagnosis of IPF will be confirmed by the PI using ATS/ERS/JRS/ALAT consensus criteria 
(Raghu et al, 2011 or Raghu et al, 2018).  
Clinical management of the patient at the site must be for IPF and the PI must be convinced that 
all locally available information support that UIP/IPF is the most likely diagnosis. It is 
mandatory that the PI consider overreader interpretation of Visit 1b HRCT and, if performed, 
SLB in order to determine that a subject is eligible for this trial. 
The diagnosis of IPF may be made on the basis of HRCT and, when performed, SLB patterns in 
accordance with respective tables in the guidelines. Additional clinical data may also be used. In 
accordance with local implementation of the guidelines the diagnosis of IPF may also be 
established by review of the case at multidisciplinary discussion (MDD). 
Documentation of the diagnosis must be included in the subject’s source records. 


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11.3. 
Pharmacokinetics 
Details regarding PK sample collection and processing will be provided in the Lab Manual. 
Samples will be batched and analyzed throughout the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 


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11.4. 
Pharmacodynamics 
 
 
 
 
  
 
 
 
 
 
 
 


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12. 
STUDY PROCEDURES  
All study visits, assessments, and procedures involving study subjects will be performed at a 
Sponsor-approved Investigator site, and assessments and procedures will be performed by study 
center personnel under the supervision of the Investigator. The Investigator may perform 
unscheduled assessments not specified in this protocol to ensure subject safety. All 
measurements performed and results obtained during the study will be recorded in the eCRF. 
The informed consent form (ICF) should be signed before Visit 1a to allow the site to instruct the 
subject to withhold bronchodilator use as required for the PFT (Section 11.2.2) 
 
 A signed and 
dated ICF will be obtained from the subject as required by the protocol before any Screening 
procedures are conducted. A signed copy of the ICF will be given to the subject.  
Subjects should be dosed on the study day listed in the Study Schedule (± 4 days for Visit 3 or ± 
7 days for Visits 4 to 13), ensuring a minimum of 7 days between each dose. Assessments not 
associated with study treatment infusion may be performed on days other than the dosing day for 
scheduling purposes, as long as they are performed before the infusion. 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.1. 
Screening 
Screening begins with the first Visit 1a procedure (excluding signing the ICF) and may be 
shorter than 42 days.
 
ALL Visit 1a 
procedures MUST be completed before any Visit 1b procedures may be started. 
 
 
 
 
 
 
12.1.1. 
Visit 1a 
The following procedures will be performed: 
• Record demographics and baseline characteristics. 
• Record medical history (events that occurred prior to 24 hours before Visit 1a) and 
record AEs (events that occur beginning 24 hours before Visit 1a). 
• Record IPF history and previous IPF treatments. 
• 
 
• Record prior medication use (medications taken within 14 days before Visit 1a until 
24 hours before Visit 1a; see Section 10.3.1) and concomitant medications 
(medications taken beginning 24 hours before Visit 1a; see Section 10.3.2). 


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• Conduct complete physical examination, including height and weight.  
• Perform 12-lead ECG. 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 before collection of blood samples. 
• 
 
• Collect urine sample for: 
− urine pregnancy test (female subjects of childbearing potential only) 
− urinalysis 
• Collect blood samples for the following tests: 
− chemistry  
− hematology  
− 
 
 
− serology (hepatitis B surface antigen [HBsAg], hepatitis C antibody [HCV Ab], 
and HIV 1/2 antibodies)  
• SARS-CoV-2 virus or viral antigen test (See Section 8.3.3) 
• Verify and document all inclusion and exclusion criteria, and determine subject 
eligibility. 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.1.2. 
Visit 1b 
The following procedures will be performed: 
• Confirm all inclusion and exclusion criteria, and confirm subject’s eligibility for 
study participation. 
• Record AEs and the status of unresolved AEs. 
• Record concomitant medications. 
• Conduct an abbreviated physical examination. 
• Perform 12-lead ECG. 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 before collection of blood samples. 
• 
  
• Collect blood for hemoglobin analysis. 
• 
 


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Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.2. 
Treatment Period (Days 1 [Baseline] to 168) 
12.2.1. 
Visit 2 (Days 1 to 2) 
 
 
 
12.2.1.1. Day 1 
The following procedures will be performed on Day 1 before the start of the study treatment 
infusion: 
• Confirm all inclusion and exclusion criteria and confirm subject’s eligibility for study 
participation. 
• Record AEs and the status of unresolved AEs. 
• Record concomitant medications. 
• Conduct an abbreviated physical examination. 
• Collect urine sample for urine pregnancy test (female subjects of childbearing 
potential only). 
• Complete randomization procedure using IWRS schedule. Store randomization 
assigned in the Pharmacy Manual to prevent unblinding. 
• 
 
• Collect blood for the following tests: 
− chemistry 
− hematology 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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• Administer premedications, if applicable (see Section 18.5).  
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 once before the study treatment infusion (if 
premedication is administered, vital signs should be measured after premedication). 
• Administer assigned study treatment. 
The following procedures will be performed on Day 1 during the study treatment infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 midinfusion ± 5 minutes (if infusion is administered 
at a modified rate 
 the timing should correspond to 
the middle of the modified infusion duration). 
• 
 
 
The following procedures will be performed on Day 1 after the end of the study treatment 
infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 within 15 minutes after the end of the study treatment 
infusion. 
• 
 
 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.2.1.2. Day 2 
• Study personnel will call subjects not returning to the site to collect any AEs and 
concomitant medications that may have occurred after leaving the site on Day 1. 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.2.2. 
Visit 3 (Day 15) All Subjects 
Visit 3 will be conducted 14 ± 4 days after the previous dose of study treatment. The following 
study procedures will be performed at Visit 3 before the study treatment infusion:  
• Record AEs and the status of unresolved AEs. 
• Record concomitant medications. 


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• Collect blood for the following tests: 
 
 
 
 
 
 
 
 
• Administer premedications, if applicable (see Section 18.5). 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 once before the study treatment infusion (if 
premedication is administered, vital signs should be measured after premedication). 
• Administer assigned study treatment. 
The following study procedures will be performed at Visit 3 during the study treatment infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 midinfusion ± 5 minutes (if infusion is administered 
at a modified rate 
 the timing should correspond to 
the middle of the modified infusion duration). 
The following study procedures will be performed at Visit 3 after the study treatment infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 within 15 minutes after the end of the study treatment 
infusion. 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.2.3. 
Visit 4 (Day 29) All Subjects 
Visit 4 will be conducted 14 ± 7 days after the previous dose of study treatment. The following 
study procedures will be performed at Visit 4 before the study treatment infusion: 
• Record AEs and the status of previously unresolved AEs. 
• Record concomitant medications. 
• 
 
• Collect urine sample for urine pregnancy test (female subjects of childbearing 
potential only). 
• Collect blood for the following tests: 
− chemistry 
− hematology 


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• Administer premedications, if applicable (see Section 18.5). 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 once before the study treatment infusion (if 
premedication is administered, vital signs should be measured after premedication). 
• Administer assigned study treatment. 
The following study procedures will be performed at Visit 4 during the study treatment infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 midinfusion ± 5 minutes (if infusion is administered 
at a modified rate 
 the timing should correspond to 
the middle of the modified infusion duration). 
The following study procedures will be performed at Visit 4 after the study treatment infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 within 15 minutes after the end of the study treatment 
infusion. 
• Perform 12-lead ECG once, within 30 minutes after the end of the study treatment 
infusion. 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.2.4. 
Visits 5, 7, 9, 11, and 13 (Days 43, 71, 99, 127, 155) All Subjects 
Each of Visits 5, 7, 9, 11, and 13 will be conducted 14 ± 7 days after the previous dose of study 
treatment. The following study procedures will be performed at these visits before the study 
treatment infusion: 
• Record AEs and the status of previously unresolved AEs. 
• Record concomitant medications. 
• 
 
 
• Administer premedications, if applicable (see Section 18.5). 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 once before the study treatment infusion (if 
premedication is administered, vital signs should be measured after premedication). 
• Administer assigned study treatment. 


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The following study procedures will be performed at these visits during the study treatment 
infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 midinfusion ± 5 minutes (if infusion is administered 
at a modified rate 
 the timing should correspond to 
the middle of the modified infusion duration). 
The following study procedures will be performed at these visits after the study treatment 
infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 within 15 minutes after the end of the study treatment 
infusion. 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.2.5. 
Visits 6, 8, 10, and 12 (Days 57, 85, 113, and 141) All Subjects 
Each of Visits 6, 8, 10, and 12 will be conducted 14 ± 7 days after the previous dose of study 
treatment. The following study procedures will be performed at these visits before the study 
treatment infusion: 
• Record AEs and the status of previously unresolved AEs. 
• Record concomitant medications. 
• Collect urine sample for urine pregnancy test (female subjects of childbearing 
potential only) 
• 
 
• Collect blood for the following tests: 
− chemistry 
− hematology 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 


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• Administer premedications, if applicable (see Section 18.5). 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 once before the study treatment infusion (if 
premedication is administered, vital signs should be measured after premedication). 
• Administer assigned study treatment. 
The following study procedures will be performed at these visits during the study treatment 
infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 midinfusion ± 5 minutes (if infusion is administered 
at a modified rate 
, the timing should correspond to 
the middle of the modified infusion duration). 
The following study procedures will be performed at these visits after the study treatment 
infusion: 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 within 15 minutes after the end of the study treatment 
infusion. 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.3. 
End-of-Treatment (Visit 14 [Day 169]/Early Termination) 
Visit 14/ET will be conducted 14 ± 7 days after the final dose of study treatment. The following 
study procedures will be performed at this visit:  
• Record AEs and the status of previously unresolved AEs. 
• Record concomitant medications. 
• Perform a complete physical examination, including weight. 
• Perform a 12-lead ECG. 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 before collection of blood samples. 
 
 
 
 
  
 
 


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• Collect urine sample for:  
− urinalysis 
− urine pregnancy test (female subjects of childbearing potential only) 
• Collect blood for the following tests: 
− chemistry 
− hematology 
 
 
 
 
 
 
 
 
 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.4. 
Follow Up  
12.4.1. 
Follow-Up Visit 1 (Visit 15/Day 197) 
The FU visit will be conducted 4 weeks (± 7 days) after Visit 14/ET (ie, 6 weeks [± 7 days] after 
the final dose of study treatment). The following study procedures will be performed at this visit:  
• Record AEs and the status of previously unresolved AEs. 
• Record concomitant medications. 
• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 before collection of blood samples. 
• Collect urine sample for urine pregnancy test (female subjects of childbearing 
potential only) 
 
 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 
12.4.2. 
Follow-Up Visit 2 (Visit 16/Day 239) 
The second FU visit will be conducted 10 weeks (± 7 days) after Visit 14/ET (ie, 12 weeks 
[± 7 days] after the final dose of study treatment). The following study procedures will be 
performed at this visit:  
• Record AEs and the status of previously unresolved AEs. 
• Record concomitant medications. 


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• Measure vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, 
and oral temperature) and SpO2 before collection of blood samples. 
 
 
 
 
• Collect urine sample for:  
− urinalysis 
− urine pregnancy test (female subjects of childbearing potential only) 
• Blood will be collected for the following tests: 
− chemistry 
− hematology 
 
 
 
 
Refer to Section 18.6 for guidance on clinical trial conduct relating to COVID-19. 


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13. 
STATISTICS 
In addition to this section of the study protocol, a Statistical Analysis Plan (SAP) will be 
developed and finalized prior to the final database lock and unblinded data analysis. The SAP 
will provide a detailed description for the handling of missing data, subject eligibility criteria for 
the analysis, and statistical methodology for the data summary and between-group comparisons. 
Statistical analysis will be done by the Sponsor or under the authority of the Sponsor. A general 
description of the statistical methods to be used to analyze the safety and efficacy data is outlined 
below. Specific details will be provided in the SAP. 
Additional sensitivity analyses may be performed due to the COVID-19 pandemic. All analyses 
related to COVID-19 will be conducted in accordance with regulatory guidelines. These analyses 
will be described in the SAP. 
13.1. 
Study Endpoints 
13.1.1. 
Primary Endpoint 
13.1.1.1. Safety 
• Incidence of TEAEs and treatment-emergent SAEs 
• Proportion of subjects discontinuing study treatment due to TEAEs 
13.1.2. 
Secondary Endpoint 
13.1.2.1. Biological Activity 
• Rate of decline in FVC over 24 weeks (measured in mL and % of predicted over unit 
time) 
• Absolute and relative change in FVC (mL and % of predicted) at Visit 14 (Day 169) 
as compared with baseline  
• Proportion of subjects with an FVC response (mL and % of predicted) defined as 
either having improvement or a decline by 0% to ≤ 5%, > 5% to ≤ 10%, and by 
> 10% at Visit 14 (Day 169) 
• Change in DLCO and DLCO corrected for hemoglobin 
• Changes of ILA as measured by HRCT (ie, change in parenchymal feature [Baseline 
to Visit 14 (Day 169)]), as determined by qualitative assessment (central radiologist) 
and quantitative analysis (Quantitative Lung Fibrosis – QLF analysis) 
• Time to first acute IPF exacerbation (ie, an unexplained worsening of dyspnea, 
evidence of hypoxemia as defined by worsened or severely impaired gas exchange, 
new radiographic alveolar infiltrates, and an absence of an alternative explanation 
such as infection, pulmonary embolism, pneumothorax, or heart failure [Raghu et al, 
2011]) 


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• Rate of hospitalization for respiratory ailments, rate of mortality due to all causes, and 
rate of deterioration of IPF resulting in lung transplantation (up to 12 weeks after the 
end of study treatment) or death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
13.2. 
Statistical Plan 
13.2.1. 
Populations of Interest 
Safety Population: The safety population will include all subjects who receive at least 1 dose of 
study treatment. 
ITT Population: The intent-to-treat (ITT) population will include any randomized subjects. 
PK Population 1: This PK population will include subjects in the PK subset who receive at least 
1 dose of study treatment and have a majority of scheduled PK samples drawn for serial PK 
measurements that allow for PK parameters to be generated. Subjects who do not complete the 
study treatment infusion (Visit 2) will be excluded from PK analysis. 
PK Population 2: This PK population will include subjects who receive the majority of the study 
treatment doses and also have a majority of the planned trough samples collected that allow for a 
comparison of trough levels across dosing weeks. 
Per Protocol: This population will exclude nonevaluable subjects and subjects with major 
protocol deviations thought to impact the ability to assess the effect of study treatment. 
Exclusion of subjects from the Per Protocol (PP) set will be reviewed, documented, and 
approved before the study is unblinded to the study Sponsor. The criteria for excluding subjects 
from the PP population will be specified in the SAP. 
13.2.2. 
Demographic and Baseline Characteristics  
The safety population will be used for summary of demographic and baseline characteristics. 


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Demographic and baseline laboratory results will be summarized overall and by treatment arm 
using descriptive statistics. Additionally, the proportion of subjects on SOC upon randomization 
for each treatment arm will be summarized.   
13.2.3. 
Safety 
All safety analyses will be performed on the safety population. 
The analysis of safety, reported for each treatment arm, will be based on the frequency of AEs 
and their severity for all treated subjects. The safety variables, including AEs, SAEs, and AEs of 
interest (coded using the Medical Dictionary for Regulatory Activities [MedDRA]), clinical 
laboratory tests 
 physical 
examination, ECGs, and vital signs will be summarized or tabulated by treatment arm. Some of 
the variables will be tabulated by treatment arm and by visit. Incidence of AEs will be further 
tabulated by subjects on SOC within each treatment arm. 
The proportion of subjects discontinuing study treatment due to AEs will be tabulated by 
treatment arm. 
13.2.4. 
Biological Activity  
All biological activity analyses will be performed on the ITT population. 
 
 
  
 
 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
  
 


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13.2.5. 
Pharmacokinetics  
 
 
 
 
 
  
 
 
 
 
 
 
 


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13.3. 
Determination of Sample Size 
Approximately 120 subjects will be enrolled into the study, with approximately 40 subjects in 
each of 3 arms. The study will include approximately 35-40 sites and will enroll approximately 
3 to 5 subjects per site. 
 
 
 
13.4. 
Deviation from Original Analysis Plan 
All deviations from the original SAP will be provided in the final clinical study report.  


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14. 
ADVERSE EVENTS 
14.1. 
Adverse Event Definitions 
14.1.1. 
Adverse Event 
An AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug-related. An AE (also referred to as an adverse experience) can be 
any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a drug and does not imply any judgment about causality. 
An AE can arise with any use of the drug (eg, off-label use, use in combination with another 
drug) and with any route of administration, formulation, or dose, including an overdose. 
14.1.2. 
Suspected Adverse Reaction  
Any AE for which there is a reasonable possibility that the drug caused the AE. For the purposes 
of Investigational New Drug (IND) safety reporting, ‘‘reasonable possibility’’ means there is 
evidence to suggest a causal relationship between the drug and the AE. Suspected adverse 
reaction implies a lesser degree of certainty about causality than adverse reaction, which means 
any AE caused by a drug. 
14.1.3. 
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse 
Reaction 
An AE or suspected adverse reaction is considered ‘‘life-threatening’’ if, in the view of either the 
Investigator or Sponsor, its occurrence places the subject at immediate risk of death. It does not 
include an AE or suspected adverse reaction that, had it occurred in a more severe form, might 
have caused death. 
14.1.4. 
Serious Adverse Event or Serious Suspected Adverse Reaction  
An AE or suspected adverse reaction is considered ‘‘serious’’ if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening AE – see definition above  
• Admission to the hospital or prolongation of existing hospitalization1 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect  
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include allergic 
 
1 Admission to the hospital for a scheduled PK blood sample collection will not be considered an SAE. If the 
planned hospitalization should be prolonged due to an AE, an SAE would need to be documented. 


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bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
14.1.5. 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction 
An AE or suspected adverse reaction is considered ‘‘unexpected:’’  
• If it is not listed in the Investigator Brochure or is not listed at the specificity or 
severity that has been observed, or  
• If an Investigator Brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the current 
application, as amended.  
For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the Investigator Brochure referred only to elevated hepatic enzymes or hepatitis. 
Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of 
greater specificity) if the Investigator Brochure listed only cerebral vascular accidents.  
‘‘Unexpected,’’ as used in this definition, also refers to AEs or suspected adverse reactions that 
are mentioned in the Investigator Brochure as occurring with a class of drugs or as anticipated 
from the pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation. 
14.2. 
Adverse Event Classification 
14.2.1. 
Treatment-Emergent Adverse Events 
An AE is defined as treatment-emergent if it occurs at or after the first dose of study treatment 
and through 2 weeks after the last dose of study treatment. This also includes AEs which are 
observed before the first dose of study treatment and increase in severity after the first dose 
through 2 weeks after the last dose of study treatment. 
Note: 2 weeks after the last dose of study treatment was selected because it is expected to be 
longer than 5 times the terminal half-life of ND-L02-s0201. 
 
 
 
 
 
  
14.2.4. 
Respiratory Adverse Events 
It is recognized that exacerbations of IPF occur and that they may be preceded by indolent 
symptoms. These indolent symptoms should be recorded per the site’s customary practices for 
reporting AE. When a subject’s status progresses to include sufficient respiratory deterioration, 
imaging findings, histopathology, and/or clinical interventions consistent with exacerbation of 
IPF, AE reporting should convert to this term as long as it is the same event. If the Investigator 


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determines that there is a relationship between the AE (eg, upper respiratory tract infection) and 
the exacerbation, the former term should be modified to indicate the relationship (eg, upper 
respiratory tract infection preceding IPF exacerbation or upper respiratory tract infection-related 
to IPF exacerbation). If the time-relationship is unclear, separate AEs are appropriate and IPF 
exacerbation should be captured as a new event.  
14.2.5. 
Acute Exacerbation of IPF 
Idiopathic pulmonary fibrosis exacerbation is defined as an unexplained worsening of dyspnea, 
evidence of hypoxemia as defined by worsened or severely impaired gas exchange, new 
radiographic alveolar infiltrates, and an absence of an alternative explanation such as infection, 
pulmonary embolism, pneumothorax, or heart failure (Raghu et al, 2011). 
 
 
 
 
 
 
 
 
 
 
 
 
14.2.7. 
Relationship to Study Treatment, Premedication, and Standard of Care 
Relationship to study treatment, premedication, and standard of care will be assessed. Hereafter 
referred to as drug in this section. 
The Investigator’s assessment of causality must be provided for all AEs (serious and nonserious). 
An Investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the drug caused or contributed to an AE. The possibility of a causal relationship 
means that there are facts, ie, evidence, or arguments to suggest a causal relationship. Adverse 
events with a relationship of “none” are considered not related to drug. All other AE relationship 
(unlikely, possible, probable, and definite) are considered related to drug. 
Clinical judgement should be used to determine the relationship of drug to the AE. The 
Investigator should consider, for example, all relevant and/or alternative causes, including 
pattern of the reaction, temporal relationship, de-challenge, re-challenge, underlying disease(s), 
concomitant therapy(ies), concomitant illness(es), risk factor(s), and medical history. 
None: 
No relationship between the experience and the administration of drug; related to 
other etiologies such as concomitant medications or subject’s clinical state. 


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Unlikely: 
The current state of knowledge indicates that a relationship is unlikely. However, 
as a causal relationship to the drug cannot be ruled out, the causal relationship 
will be classified as related to drug. 
Possible: 
A reaction that follows a plausible temporal sequence from administration of the 
drug and follows a known response pattern to the suspected drug. The reaction 
might have been produced by the subject’s clinical state or other modes of therapy 
administered to the subject, but this is not known for sure. 
Probable: 
A reaction that follows a plausible temporal sequence from administration of the 
drug and follows a known response pattern to the suspected drug. The reaction 
cannot be reasonably explained by the known characteristics of the subject’s 
clinical state or other modes of therapy administered to the subject. 
Definite: 
A reaction that follows a plausible temporal sequence from administration of the 
drug and follows a known response pattern to the suspected drug and can be 
confirmed with a positive re-challenge test or supporting laboratory data. 
Note: AEs that occur after administration of premedication (if applicable) but before the 
administration of study treatment should not be reported as related to study treatment. 
Refer to the country-specific package insert of Summary or Product Characteristics for the risks 
and side effects associated with pirfenidone, nintedanib, and premedication (if applicable). 
14.2.8. 
Severity 
Grading of AEs will be done using the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events version 5.0 (CTCAE v5.0) 
(https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50).  
If an AE is not listed in the CTCAE v5.0, then the Investigator will use the terms: mild, 
moderate, severe, life-threatening, or death to describe the maximum intensity of the AE. For 
purposes of consistency, these intensity grades are defined as follows: 
Grade 1 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
Grade 2 
Moderate 
Minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily 
livinga 
Grade 3 
Severe or medically significant 
but not immediately life-
threatening 
Hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care activities of daily 
livingb 
Grade 4 
Life threatening consequences 
Urgent intervention indicated 
Grade 5 
Death 
Death related to an adverse event 
a Instrumental activities of daily life refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc 
b Self-care activities of daily life refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 


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14.3. 
Exposure in Utero 
The subject will be instructed to notify the Investigator if the subject or subject’s partner 
becomes pregnant during the study, The Investigator must notify the Sponsor within 24 hours, 
and must complete the Pregnancy Notification Form and submit it to the Sponsor within 
2 working days of being notified. The Investigator should obtain informed consent/assent from 
the subject or subject’s partner allowing the Investigator to obtain information regarding the 
pregnancy and its outcome. If the subject or subject’s partner provides informed consent/assent, 
the Investigator should follow the pregnancy until outcome. A final Pregnancy Notification Form 
should be completed when the outcome of the pregnancy is known. 
14.4. 
Monitoring of Adverse Event Data 
To ensure safety of the overall study an independent DMC will be established. The DMC will 
periodically review the safety and tolerability of study treatment for the duration of the study. 
Refer to Section 7.4 for details.  
14.5. 
Documentation of Adverse Events by Investigator 
Subjects will be evaluated and questioned generally to identify AEs during the course of the 
study. Adverse event collection will begin 24 hours before Visit 1a. Adverse events that occur up 
to and including 12 weeks after administration of the last dose of study treatment, including ET, 
must be reported. 
All AEs spontaneously reported by the subject and/or in response to an open question from study 
personnel or revealed by observation, physical examination, or other diagnostic procedures will 
be recorded on the Adverse Event Form for that visit. Any clinically relevant deterioration in 
laboratory assessments, intercurrent illness, or other clinical findings is considered an AE and 
must be recorded on the Adverse Event Form. In addition, an abnormal test finding will be 
classified as an AE if one or more of the following criteria are met: 
• The test finding is accompanied by clinical symptoms. 
• The test finding necessitates additional diagnostic evaluation(s) or medical/surgical 
intervention; including significant additional concomitant drug treatment or other 
therapy. Note: simply repeating a test finding, in the absence of any of the other listed 
criteria, does not constitute an AE. 
• The test finding leads to a change in study treatment dosing or discontinuation of 
subject participation in the clinical research study. 
• The test finding is considered an AE by the Investigator. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified. However, if an observed or reported sign or symptom is not 
considered a component of a specific disease or syndrome by the Investigator, it should be 
recorded as a separate AE. Laboratory data will be collected as stipulated in this protocol. 
Clinical syndromes associated with laboratory abnormalities will be recorded as appropriate 
(eg, diabetes mellitus rather than hyperglycemia). 


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For SAEs, a Serious Adverse Event Form must also be completed with as much information as 
possible and submitted in the time frame described below in Section 14.6. When new significant 
information is obtained as well as when the outcome of an event is known, the Investigator 
should record the information on a new SAE form. If the subject was hospitalized, a copy of the 
discharge summary and any other relevant hospital records (eg, admission report, laboratory test 
results, etc.) must be included as part of the subject medical file.  
The clinical course of each AE will be followed until resolution, stabilization, or until it has been 
determined that the study treatment or participation is not the cause.  
14.6. 
Notification about Serious Adverse Events and Serious and 
Unexpected Suspected Adverse Reactions 
14.6.1. 
Investigator Reporting to Sponsor 
All SAEs that occur during the course of the study must be reported by the Investigator to the 
Sponsor, designated representative, and Medical Monitor within 24 hours by fax or email. In 
addition, all SAEs that occur up to and including 12 weeks after administration of the last dose of 
study treatment must be reported to the Sponsor within 24 hours from when the Investigator 
becomes aware of the SAE. 
Investigators must report to the Sponsor all SAEs, whether or not considered drug-related, 
including those listed in the Investigator Brochure. The report must include an assessment of 
causality.  
For all SAEs, the Investigator is obligated to obtain and provide information to the Sponsor in 
accordance with the timeframes for reporting specified above. In addition, an Investigator may 
be requested by the Sponsor to obtain specific additional follow-up information in an expedited 
fashion. This information may be more detailed than that captured on the AE CRF. In general, 
this will include a description of the AE in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality. Information on other 
possible causes of the event, such as concomitant medications and illnesses must be provided. In 
the case of a subject death, a summary of available autopsy findings must be submitted as soon 
as possible to the Sponsor or its designated representative. 
 
 
 
 
 
 
14.6.2. 
Reporting to Regulatory Agencies and Institutional Review Boards/Independent 
Ethics Committees 
If there is a serious and unexpected suspected adverse reaction, the Sponsor will notify the 
appropriate regulatory agency(ies) on an expedited basis. In addition, Sponsors must submit 
expedited reports of an increased rate of occurrence of serious suspected adverse reactions over 
that listed in the Reference Safety Information. 


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It is the responsibility of the Investigator to promptly notify the Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) of all serious and unexpected suspected adverse 
reactions involving risk to human subjects. 
14.7. 
Emergency Identification of Study Medication 
In the event of a medical emergency, when knowledge of the subject’s treatment assignment may 
influence the subject’s clinical care, the Investigator may obtain the treatment assignment of the 
subject experiencing the emergency. The Investigator can unblind individual subjects via the 
study IWRS. The Investigator will create a secure account and receive a username and password 
prior to enrolling subjects. After unblinding, the Investigator should contact the Medical 
Monitor. 
If unblinding is necessary, the Investigator must document the reasons for unblinding in the 
subject’s source documents but should not divulge the subject’s treatment assignment to any 
individuals except the Medical Monitor and those individuals involved in the direct care of the 
subject. The date and the reasons for breaking the blind must be submitted to the Sponsor within 
24 hours.  
If a subject’s treatment assignment is unblinded, the subject should remain in the study and 
continue the protocol-specified follow-up evaluations. 
14.8. 
Emergency Sponsor Contact 
In a medical emergency, a qualified healthcare provider will attend to the subject’s immediate 
clinical management, including administration of medical intervention according to the SOC. 
 
 
 
 
 
 


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15. 
ETHICS 
15.1. 
Institutional Review Board or Independent Ethics Committee 
The IRB/IEC will meet all FDA and applicable regulatory authority requirements governing 
IRBs/IECs in accordance with ICH GCPs.  
The Investigator will provide the Sponsor (or designee) with documentation of IRB/IEC 
approval of the following documents before the study begins at the study site(s): protocol, ICF, 
and any other relevant materials intended for or directed to subjects (eg, subject diaries, 
advertisements). The Investigator will supply documentation to the Sponsor (or designee) of 
IRB/IEC requirements regarding continuing review and approval of revisions to any of these 
documents. 
15.2. 
Ethical Conduct of the Study 
This study will be conducted in accordance with the current IRB/IEC approved clinical protocol, 
ICH GCP Guidelines, and relevant policies and requirements of the national regulations and 
laws, including the Health Insurance Portability and Accountability Act of 1996 (HIPAA). 
15.3. 
Subject Information and Informed Consent 
Written informed consent/assent is required from each subject before any testing under this 
protocol, including Screening tests and evaluations. The ICF, as specified by the clinical site’s 
IRB/IEC, must follow the Protection of Human Subjects regulations listed in 21 Code of Federal 
Regulations (CFR) Part 50 and ICH E6 4.8.  
The ICF will be used to explain the risks and benefits of study participation in simple terms 
before the subject will be entered into the study. The ICF will contain a statement that the 
consent is freely given, that the subject is aware of the risks and benefits of entering the study, 
and that the subject is free to withdraw from the study at any time. Written informed consent 
must be given by the subject after the receipt of detailed information on the study. It is the 
responsibility of the Investigator to obtain consent/assent and to provide the subject with a copy 
of the signed and dated ICF. Confirmation of a subject’s informed consent must also be 
documented in the subject’s medical record before any testing under this protocol, including 
Screening tests and evaluations. 
All ICFs used in this study must be approved by the appropriate IRB/IEC and by the Sponsor or 
its designee. The ICF must not be altered without the prior agreement of the relevant IRB/IEC 
and the Sponsor (or designee). 


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16. 
STUDY ADMINISTRATION 
16.1. 
Administrative Structure 
A list of individuals who will have key positions in this study will be saved in the Trial Master 
File (TMF). This list will include names, titles, and roles of selected individuals from the 
Sponsor (or designee) and the Contract Research Organization (CRO) that will contribute to this 
study. 
16.2. 
Quality Control and Quality Assurance 
16.2.1. 
Overview 
According to the GCP Guidelines, the Sponsor is responsible for implementing and maintaining 
quality assurance (QA) and QC systems with written SOPs.  
QC will be applied to each stage of data handling. The following steps will be taken to ensure the 
accuracy, consistency, completeness, and reliability of the data: 
• Investigator meeting(s); 
• Site initiation visit; 
• Routine site monitoring; 
• Ongoing site communication and training; 
• Data management quality control checks; 
• Continuous data acquisition and cleaning; 
• Internal review of data; and 
• QC checks of the final clinical study report (CSR). 
In addition, the Sponsor’s (or designee) Clinical QA Department may conduct periodic audits of 
the study processes, including, but not limited to study site, site visits, vendors, clinical database, 
and final CSR. When audits are conducted, access must be authorized to Sponsor’s 
representatives and regulatory authorities for all study-related documents, including medical 
history and concomitant medication documentation. 
16.2.2. 
Risk Management 
Program risks will be evaluated on an ongoing basis by the Sponsor in accordance with ICH 
E6 (R2) Section 5, and any important deviations from prespecified quality limits will be 
documented in the clinical study report. 
16.2.3. 
Monitoring 
The Sponsor has engaged the services of a CRO to perform all monitoring functions for this 
clinical study. Monitors will work in accordance with the CRO’s SOPs and have the same rights 
and responsibilities as monitors from the Sponsor organization. Monitors will establish and 
maintain regular contact between the Investigator or designee and the Sponsor. 


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Monitors will evaluate the competence of each study site, informing the Sponsor about any 
problems relating to facilities, technical equipment, or medical staff. During the study, monitors 
will check that written informed consent/assent has been obtained from all subjects correctly and 
that data are recorded correctly and completely on the eCRFs. Monitors are also required to 
compare entries in eCRFs with corresponding source data and to inform the Investigator or 
designee of any errors or omissions. Monitors will also review adherence to the protocol and to 
regulatory requirements at the study site and discuss and deviations noted with the Investigator 
or designee. They will arrange for the study site to receive adequate supply of IP, review IP 
accountability records to IP supplies/subject use, and ensure appropriate storage conditions are 
maintained.  
In the event that onsite monitoring visits are not allowed due to health safety concerns, monitors 
will remotely monitor data entry into the database by site staff and may perform source data 
verification (if allowed by the site) to identify SAEs that may not have been reported by sites. As 
soon as feasible, onsite monitoring will resume, and data monitored remotely will be source data 
verified. 
Monitoring visits will be conducted according to the United States CFR Title 21 parts 50, 56, and 
312 and ICH Guideline for GCP. The monitor will make written reports to the Sponsor following 
each contact with the Investigator or designee, regardless of whether it is by phone or in person. 
16.2.4. 
Data Management/Coding 
Study data will be handled according to the relevant SOPs of the data management and 
biostatistics departments of the Sponsor (or designee) or CRO. 
AEs will be coded using MedDRA and medications will be coded using World Health 
Organization (WHO) Drug Dictionary Enhanced (WHODDE) drug dictionary. 
16.2.5. 
Quality Assurance Audit 
Study sites, the study database and study documentation may be subject to a QA audit by the 
Sponsor or designee on behalf of the Sponsor. In addition, inspections may be conducted by 
regulatory bodies at their discretion. 
16.3. 
Data Handling and Recordkeeping 
16.3.1. 
Electronic Data 
When using electronic trial data handling and/or remote electronic trial data systems, the Sponsor 
(or designee) will: 
• Ensure and document that the electronic data processing system(s) conforms to the 
Sponsor’s established requirements for completeness, accuracy, reliability, and 
consistent intended performance (ie, validation) 
• Maintain SOPs for using these systems 
• Ensure that the systems are designed to permit data changes in such a way that the 
data changes are documented and that there is no deletion of entered data (ie, 
maintain an audit trail, data trail, edit trail) 


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• Maintain a security system that prevents unauthorized access to the data 
• Maintain a list of the individuals who are authorized to make data changes 
• Maintain adequate backup of the data 
• Safeguard the blinding, if any (eg, maintain the blinding during data entry and 
processing) 
Documentation regarding electronic systems used in this protocol is available upon request from 
the CRO maintaining the electronic trial data system. 
16.3.2. 
Case Report Form Completion 
Electronic data capture will be used for the study. All data will be recorded on source 
documentation at each study location and entered electronically by the study center personnel. 
Data collected on each subject will be documented on the appropriate eCRF. Completed eCRFs 
will be signed off by the Investigator or his/her designee. 
16.3.3. 
Data Handling 
If data are transformed during processing, records will be maintained so that it will be possible to 
compare the original data and observations with the processed data. 
An unambiguous subject identification code will be used that allows identification of all the data 
reported for each subject. 
16.3.4. 
Retention of Study Records 
The Investigator must maintain essential study documents (protocol and protocol amendments, 
completed eCRFs, signed ICFs, relevant correspondence, and all other supporting 
documentation) until at least 2 years after the last approval of a marketing application in an ICH 
region and until there are no pending or contemplated marketing applications in an ICH region or 
at least 2 years after the formal discontinuation of clinical development of the IP. These 
documents will be retained for a longer period if required by the applicable regulatory 
requirements or the hospital, institution, or private practice in which the study is being 
conducted. Subject identification codes (subject names and corresponding study numbers) will 
be retained for this same period of time. These documents may be transferred to another 
responsible party, acceptable to the Sponsor, who agrees to abide by the retention policies. 
Written notification of transfer must be submitted to the Sponsor. The Investigator or designee 
must contact the Sponsor before disposing of any study records. 
16.4. 
Financing and Insurance 
Financing and insurance are addressed in a separate document. 
16.5. 
Confidentiality 
To maintain subject privacy, all eCRFs, study treatment accountability records, study reports and 
communications will identify the subject by the assigned subject number. The Investigator will 
grant monitor(s) and auditor(s) from the Sponsor or its designee and regulatory authority(ies) 
access to the subject’s original medical records for verification of data gathered on the eCRFs 


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and to audit the data collection process. The subject’s confidentiality will be maintained in 
accordance with applicable laws and regulations. 
Subjects will be informed that registration information, results, and other information about this 
study will be submitted to publicly available clinical trial registry databases in the United States, 
European Union, and Japan; however, protected health information of individual subjects will 
not be used. 
All information regarding the IP supplied by the Sponsor to the Investigator is privileged and 
confidential information. The Investigator agrees to use this information to accomplish the study 
and will not use it for other purposes without consent from the Sponsor. It is understood that 
there is an obligation to provide the Sponsor with complete data obtained during the study. The 
information obtained from the clinical study will be used toward the development of the IP and 
may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or 
consultants as required. 
16.6. 
Publication Policy 
The data generated by this study are considered confidential information and the property of 
Sponsor and shall not be published or disclosed without the prior written consent of Sponsor. 
16.7. 
Direct Access to Source Data 
The Investigators/institutions clinical sites will permit trial-related monitoring, audits, IRB/IEC 
review, and regulatory inspections as requested by FDA or other regulatory authorities, the 
Sponsor, or the Sponsor designee, including direct access to source data/documents (ie, original 
medical records, laboratory reports, hospital documents, progress reports, signed ICFs, etc) in 
addition to eCRFs. 
The Investigator or designee will prepare and maintain adequate and accurate source documents 
to support all observations and other pertinent data recorded on the eCRFs for each subject 
enrolled in the study.   
The Investigator will allow the Sponsor (or designee) and authorized regulatory authorities to 
have direct access to all documents pertaining to the study. 
16.8. 
Protocol Amendments 
Changes to the conduct of the study should be prepared as a protocol amendment and 
implemented only upon joint approval of the Sponsor, or a representative of the Sponsor, and the 
Investigator. Protocol amendments should also receive written IRB/IEC approval before 
implementation, except when necessary to eliminate immediate hazards to the subjects or when 
the changes involve only logistical or administrative aspects of the trial (eg, change of monitor, 
telephone numbers). In this case, the Sponsor will amend and implement the protocol change and 
subsequently notify the regulatory authorities and/or the IRB/IEC, as appropriate. 


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18. 
APPENDICES 
 
 
 


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18.5. 
Appendix E: Premedication 
Subjects may be premedicated to mitigate the risk of infusion-related reactions at the discretion 
of the Investigator. 
18.5.1. 
Premedications 
At Investigator discretion, a subject may be premedicated with: 
• H1 antagonist with local regulatory approval for marketing at a dose equivalent to 
50 mg diphenhydramine AND H2 antagonist with local regulatory approval for 
marketing at a dose equivalent to 20 mg famotidine 
OR 
• Systemic corticosteroid. 
Premedications will be obtained commercially by the study center. Whenever available, 
premedication should be done with preservative-free injectable formulations.  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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18.5.3. 
Documentation 
All premedication(s) administered will be reported on the appropriate eCRF. 


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18.6. 
Appendix F: Restrictions Relating to COVID-19 
This section describes safety measures that were taken due to the COVID-19 pandemic. These 
measures will also apply to subsequent outbreaks/pandemics resulting from SARS-CoV-2 
infections. 
18.6.1. 
Restrictions to Study Conduct 
The following will be taken into consideration when determining whether there are any 
restrictions to conducting onsite visits: 
• Local government/institution and hospital readiness to allow clinical research 
activities 
• Confirmed absence of COVID-19-related restrictions on mobility of persons (central, 
regional, & municipal government plus institutional) applicable to the trial 
candidates, subjects, or site personnel 
• Ability for clinical research associate (CRA) to perform onsite routine monitoring in 
accordance with the Monitoring Plan. 
• Confirmed ability to perform research PFT per protocol/established guidelines 
• Confirmed ability to perform research HRCT per protocol/established guidelines 
• Confirmed ability to process and ship central and local laboratory samples per 
protocol/established guidelines 
• Adequate stock of study supplies including laboratory kits, personal protective 
equipment, and study treatment preparation and administration materials  
• Unrestricted courier services 
The Investigator will be responsible for determining if it is safe to proceed with onsite study 
visits at his/her site considering the requirements above. If the Investigator determines that onsite 
study procedures are not feasible based on the criteria above, they must inform the IRB/IEC and 
advise the CRA or clinical trial lead (CTL). Recommendations for how to proceed if there are 
restrictions preventing onsite visits are included Section 18.6.2. 
To resume onsite study visits, the Investigator must inform the IRB/IEC and CRA or CTL after 
considering the guidelines above. 
18.6.2. 
Study Visit Guidelines 
18.6.2.1. Consenting and Screening 
When study procedures cannot be performed onsite, the Investigator should pause consenting of 
new subjects and suspend screening procedures for already consented subjects. Subjects who 
have been consented but have not received study treatment, should be considered screen failures 
(with the option to rescreen at a later time). If the Investigator believes these activities may 
resume after considering the guidelines in Section 18.6.1, the Investigator must inform the 
IRB/IEC and CRA or CTL. 


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18.6.2.2. Managing Treatment Period Study Visits 
When onsite study procedures cannot be performed for already randomized subjects, up to 
2 scheduled Treatment Period visits may be conducted remotely. The implementation of remote 
visits allows for a maximum delay in study treatment administration of 6 weeks after the last 
dose. Section 18.6.2.4 describes what data should be collected at a minimum during a remote 
visit. 
If onsite visits can resume and study treatment can be administered ≤ 6 weeks after the last dose, 
feasible study-related procedures should resume onsite as soon as possible per Section 12.2. In 
this case, the subject should proceed with the next protocol visit and follow those procedures. 
For example, if the subject has remote Visit 4 and Visit 5, and onsite visits can resume within 
6 weeks of their last dose of study treatment, the subject will resume the study and complete 
Visit 6 study procedures. 
18.6.2.3. Managing End-of-Treatment and Follow-Up Period Visits 
Subjects Who Complete Planned Treatment Period Visits 
If a subject completes all planned Treatment Period visits, remote or onsite through Visit 13, 
Visit 14 should be conducted per Section 12.3. If it is not safe or feasible to proceed onsite, 
Visit 14 may be postponed for up to 8 weeks after the last dose. If onsite Visit 14 will not be safe 
or feasible in ≤ 8 weeks after the last dose, the visit should be conducted remotely. If at any time 
circumstances change and it becomes safe and feasible for a subject to come to the site, 
subsequent visits should be performed onsite and follow procedures per Section 12 for the visits 
described below. 
a. Visit 14 performed onsite or remotely ≤ 8 weeks after Visit 13 
b. Visit 15 performed onsite or remotely 4 ± 1 week after Visit 14 
c. Visit 16 performed onsite or remotely 10 ± 1 week after Visit 14 
Subjects Who Do Not Complete Planned Treatment Period Visits 
If a subject misses 2 Treatment Period visits as described in Section 18.6.2.2, and it is not 
expected that study treatment administration can restart ≤ 6 weeks after the last dose, perform a 
remote ET visit. If circumstances change and it becomes safe and feasible for the subject to come 
to the site, ET and Follow-Up visits should be performed onsite and follow procedures per 
Section 12. 
a. ET visit performed onsite or remotely 2 ± 1 week after the second missed visit 
b. Visit 15 performed onsite or remotely 4 ± 1 week after ET visit 
c. Visit 16 performed onsite or remotely 10 ± 1 week after ET visit 
18.6.2.4. Data Collection During Remote Visits 
During remote visits, the following information should be collected at a minimum: 
1. Concomitant medications 
2. Adverse events (If the subject reports COVID-19, ask whether the infection has been 
confirmed via testing. If possible, the test used should be recorded.) 


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3. Vital signs (Has the subject been febrile? If so, how was this detected?) 
4. Pulse oximetry and supplemental oxygen requirement (if subject has equipment at home) 
18.6.2.5. High-Resolution Computed Tomography 
 
 
  
18.6.3. 
Analysis Related to COVID-19 
Additional sensitivity analyses may be performed due to the COVID-19 pandemic. All analyses 
related to COVID-19 will be conducted in accordance with regulatory guidelines. These analyses 
will be described in the SAP. 
18.6.4. 
Clinical Study Report 
The CSR will include information specific to the COVID-19 pandemic consistent with 
regulatory guidelines. 

SAP_001.pdf: 
Document Type:  
Final Statistical Analysis Plan 
Document Date:  
13 May 2022 
Study Title:  
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety, Tolerability, Biological Activity, and PK of 
ND-L02-s0201 in Subjects with Idiopathic Pulmonary Fibrosis (IPF) 
Protocol Reference Number: ND-L02-S0201-005 
NCT Number: NCT03538301 
 
 
 
 


 
 
CONFIDENTIAL 
Page 1 of 48 
 
 
ST-AD-008 version 05 
Statistical Analysis Plan 
 
Nitto Denko Corporation 
Protocol ID: ND-L02-s0201-005 
 
 
 
Document Version: 1.0 
Document Date: May 13, 2022 
 
 
 
 
 
 
 
 
 
 


 
 
CONFIDENTIAL 
Page 2 of 48 
 
 
ST-AD-008 version 05 
Table of Contents 
1. 
Source Documents ................................................................................. 8 
2. 
Protocol Details ..................................................................................... 8 
2.1 
Study Objectives................................................................................. 8 
2.2 
Overall Study Design ........................................................................... 8 
2.3 
Sample Size and Power ....................................................................... 9 
3. 
Efficacy and Safety Variables................................................................... 9 
3.1 
Primary Endpoints ............................................................................... 9 
3.2 
Secondary Endpoints ........................................................................... 9 
 
 
3.4 
Efficacy and Safety Variables .............................................................. 10 
3.4.1 
Spirometry .......................................................................................................................... 10 
3.4.2 
Diffusion Capacity of the Lung for Carbon Monoxide (DLco) ............................................. 11 
3.4.3 
High Resolution Computed Tomography (HRCT) ................................................................ 11 
 
 
3.4.5 
Extent of Exposure .............................................................................................................. 13 
3.4.6 
Adverse Events (AEs) ........................................................................................................... 14 
3.4.7 
Laboratory Evaluations ....................................................................................................... 15 
3.4.8 
Vital Signs and Pulse Oximetry ............................................................................................ 16 
3.4.9 
Physical Examination ........................................................................................................... 17 
3.4.10 
12-Lead Electrocardiograms ............................................................................................... 17 
3.4.11 
Other Safety Assessments................................................................................................... 17 
 
 
4. 
Pharmacokinetic variables ..................................................................... 19 
 
 
 
 
 
 
 
 
 
5. 
Analysis populations ............................................................................. 21 
5.1 
Safety Population (SAF) ..................................................................... 21 


Statistical Analysis Plan 
Sponsor Name: Nitto Denko Corporation 
Sponsor Protocol ID: ND-L02-s0201-005 
 
 
 
 
CONFIDENTIAL 
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Document Date: 30-Apr-2021 
 
ST-AD-008 version 05 
 
5.2 
Intent-to-treat Population (ITT) .......................................................... 21 
5.3 
Pharmacokinetic Population 1 (PK1) .................................................... 21 
5.4 
Pharmacokinetic Population 2 (PK2) .................................................... 21 
5.5 
Per Protocol Population (PP) ............................................................... 21 
6. 
Data Handling ..................................................................................... 22 
6.1 
Time points and Visit Windows ........................................................... 22 
6.2 
Handling of Dropouts, Missing Data, and Outliers .................................. 22 
7. 
Statistical Methods ............................................................................... 23 
7.1 
General Principles ............................................................................. 23 
7.2 
Subject Disposition and Data Sets Analyzed ......................................... 25 
7.3 
Protocol Deviations ........................................................................... 25 
7.4 
Demographics and Other Baseline Characteristics ................................. 25 
7.4.1 
Medical History ................................................................................................................... 27 
7.4.2 
Previous and Concomitant Medications ............................................................................. 27 
7.5 
Efficacy ............................................................................................ 28 
7.5.1 
Primary Efficacy Analysis ..................................................................................................... 28 
7.5.2 
Secondary Efficacy Analysis ................................................................................................ 28 
7.5.3 
Sensitivity Analysis .............................................................................................................. 32 
7.5.4 
Subgroup Analysis ............................................................................................................... 32 
 
 
7.6 
Safety ............................................................................................. 34 
7.6.1 
Extent of Exposure .............................................................................................................. 34 
7.6.2 
Adverse Events .................................................................................................................... 35 
7.6.3 
Laboratory Evaluations ....................................................................................................... 37 
7.6.4 
Vital Signs and Pulse Oximetry ............................................................................................ 38 
7.6.5 
Electrocardiograms ............................................................................................................. 38 
7.6.6 
Physical Examination ........................................................................................................... 39 
7.6.7 
Other Safety Analyses ......................................................................................................... 39 
 
 
7.6.9 
Impact of COVID-19 Pandemic ............................................................................................ 40 
7.7 
Interim Analysis................................................................................ 40 


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8. 
Changes in Planned Analysis ................................................................. 40 
 
Appendices.................................................................................................. 42 
Appendix 1: 
GAP Algorithm for IPF Stage and Predicted Mortality .................. 42 
Appendix 2: 
 Schedule of visits .................................................................. 44 
Appendix 3:  FVC and %FVC Baseline Determination ........................................ 47 
Appendix 4:  HRCT Assessment ..................................................................... 48 
 


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Glossary of Abbreviations 
Abbreviation 
Term 
 
 
AE 
Adverse event 
AEOI 
Adverse events of special interest 
AIC 
Akaike’s information criterion 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AR(1) 
First-order autoregressive 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
 
 
bpm 
beats per minute 
CI 
Confidence Interval 
COVID-19 
Coronavirus disease 
CS 
Compound symmetry 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLco 
Diffusion capacity of the lung for carbon monoxide 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eDISH 
Evaluation of drug induced serious hepatotoxicity 
EOT 
End-of-Treatment 
ET 
Early Termination 
FEV1 
Forced expiratory volume in 1 second 
FVC 
Forced vital capacity 
 
 
HRCT 
High-resolution computed tomography 
ILA 
Interstitial lung abnormalities 
ILD 
interstitial lung disease  
IPF 
Idiopathic pulmonary fibrosis 
ITT 
Intention-to-treat 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
 
 
KW 
Kruskal-Wallis 
KM 
Kaplan-Meier 
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 


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Abbreviation 
Term 
NCI 
National Cancer Institute 
PD 
Pharmacodynamics 
PFT 
Pulmonary function testing 
 
 
PK 
pharmacokinetic(s) 
PP 
Per protocol 
 
 
Q2W 
Every 2 weeks 
QLF 
Quantitative lung fibrosis 
QOL 
Quality of life 
QTcF 
QT interval corrected using Fridericia’s formula 
SAE 
Serious Adverse Event 
SAF 
Safety Population 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
 
 
SLB 
Surgical lung biopsy 
SOC 
System Organ Class 
SpO2 
Peripheral capillary oxygen saturation 
TEAE 
Treatment-emergent adverse event 
TFLs 
Tables, Figures and Listings 
TOEP 
Toeplitz 
UIP 
Usual interstitial pneumonia 
ULN 
Upper limit of normal 
VA 
Alveolar volume 
WBC 
White blood cell 
WHO 
World Health Organization 
 
 
 
 


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1. Source Documents 
The Statistical Analysis Plan (SAP) was written based on the following 
documentation: 
Document 
Date 
Version 
Protocol Amendment 
17 June 2020 
5.0 
eCRF 
19 February 2021 
Prod 3.00 
2. Protocol Details 
2.1 Study Objectives 
Primary: 
 
Evaluate the safety and tolerability of ND-L02-s0201, administered at 2 dose 
levels, once every 2 weeks (Q2W) over 24 weeks, versus placebo, in 
conjunction with standard of care   
Secondary: 
 
Evaluate the biological activity of ND-L02-s0201 as measured by spirometry 
over 24 weeks 
 
Evaluate changes of interstitial lung abnormalities (ILA) as measured by high-
resolution computed tomography (HRCT) 
 
 
 
 
 
 
2.2 Overall Study Design 
This is a Phase 2, double-blind, placebo-controlled, randomized, multicenter, 
international study of 2 doses of ND-L02-s0201 for Injection, consisting of 
3 treatment arms: 2 dose levels of ND-L02-s0201, a low dose (45 mg) and a high 
dose (90 mg), will be evaluated in 2 arms; a third arm will be administered placebo. 
This study will evaluate safety, tolerability, biological activity, and PK in subjects with 
a diagnosis of idiopathic pulmonary fibrosis (IPF) with forced vital capacity (FVC) 
≥45% of predicted and diffusion capacity of the lung for carbon monoxide (DLCO) 
≥30% of predicted. 
Approximately 120 eligible subjects will be randomized 1:1:1 to 1 of following 
3 treatment arms: 
 
ND-L02-s0201 for Injection high dose (90 mg) 


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 
ND-L02-s0201 for Injection low dose (45 mg) 
 
Placebo. 
The randomization via the interactive web response system (IWRS) will be stratified 
by the receipt of standard of care at the enrollment of the study, defined as 
administration of either nintedanib or pirfenidone, or no standard of care. As there is 
no minimum number of subjects for a given strata of standard of care, balance in 
strata across the 3 treatment arms is required. 
Eligible subjects who meet the inclusion criteria and do not meet any of the exclusion 
criteria and have provided informed consent will be enrolled in the study. Subjects 
will participate in the study for approximately 40 weeks consisting of a Screening and 
Baseline period of up to 6 weeks, a treatment period of 24 weeks including a total of 
12 doses and an End-of-Treatment visit 2 weeks after the final dose (Visit 14), and 
a follow-up visit 4 and 10 weeks after Visit 14, or until they withdraw from the study 
or the study is terminated by the Sponsor. During the treatment period 
ND-L02-s0201 for Injection will be administered by intravenous (IV) infusion Q2W 
(± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days 
between each dose) for a total of 12 doses. Subjects may be premedicated to mitigate 
the risk of infusion-related reactions at the discretion of the Investigator. 
2.3 Sample Size and Power 
Approximately 120 subjects will be enrolled into the study, with approximately 
40 subjects in each of 3 arms. The study will include approximately 35-40 sites, and 
will enroll approximately 3 to 5 subjects per site. 
 
 
 
 
3. 
Efficacy and Safety Variables 
3.1 Primary Endpoints 
Safety 
 
Incidence of TEAEs and treatment-emergent SAEs  
 
Proportion of subjects discontinuing study treatment due to TEAEs 
3.2 Secondary Endpoints 
Biological Activity 


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 
Rate of decline in FVC from baseline to Visit 14 (Day 169) (measured in L and 
% of predicted over unit time) 
 
Absolute and relative change in FVC (L and % of predicted) at Visit 14 (Day 
169) as compared with baseline 
 
Proportion of subjects with an FVC response (L and % of predicted) defined as 
either having improvement or a decline by 0% to ≤ 5%, > 5% to ≤ 10%, and 
by > 10% at Visit 14 (Day 169) 
 
Change in DLCO (mL/min/mmHg) and DLCO (mL/min/mmHg) corrected for 
hemoglobin at Visit 14 (Day 169) 
 
Changes of ILA as measured by HRCT (i.e., change in parenchymal feature 
[Baseline to Visit 14 (Day 169)]), as determined by qualitative assessment 
(central radiologist) and quantitative analysis (Quantitative Lung Fibrosis – 
QLF analysis) 
 
Time to first acute IPF exacerbation (i.e., an unexplained worsening of 
dyspnea, evidence of hypoxemia as defined by worsened or severely impaired 
gas exchange, new radiographic alveolar infiltrates, and an absence of an 
alternative 
explanation 
such 
as 
infection, 
pulmonary 
embolism, 
pneumothorax, or heart failure [Raghu et al, 2011]) or death 
 
Rate of hospitalization for respiratory ailments and time to first hospitalization 
for respiratory ailments or death  
 
Rate of mortality due to all causes and overall survival  
 
Rate of deterioration of IPF resulting in lung transplantation (up to 12 weeks 
after the end of study treatment) or death and time to deterioration of IPF 
resulting in lung transplantation (up to 12 weeks after the end of study 
treatment) or death 
 
 
 
 
  
 
 
 
 
 
 
3.4 Efficacy and Safety Variables 
3.4.1 Spirometry 
Spirometry variables include forced vital capacity (FVC) and percent predicted FVC 
(%FVC). FVC will be measured in units of liters (L) and rounded to 2 decimal places. 
%FVC will be measured in percent and rounded to 2 decimal places. The spirometry 


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variables will be provided by an external vendor in a data transfer and the results will 
not be entered into the EDC system.  
 
 
 In the event that 
no baseline measurement is designated, then the baseline measurement will be the 
last non-missing value before the first infusion of study treatment. 
 
 
 
 
 
  
3.4.2 Diffusion Capacity of the Lung for Carbon Monoxide (DLco) 
Diffusion capacity of the lung for carbon monoxide (DLco) in mL*(CO/min/mmHg) 
will be provided by an external vendor in a data transfer, and the results will not be 
entered in the EDC system. DLco will be provided with and without correction for 
hemoglobin and results will be rounded 2 decimal places.  
 
 
 In the event that no baseline 
measurement is designated, then the baseline measurement will be the last non-
missing value before the first infusion of study treatment. Values not designated as 
“Accepted” in the vendor data transfer will be excluded from statistical analyses. 
When more than two valid test values are obtained at a study visit in the event a PFT 
that has passed QC shows declines from baseline that need confirmatory testing, the 
average of both values will be included in the summary table. 
3.4.3 High Resolution Computed Tomography (HRCT) 
High resolution computed tomography (HRCT) data will be provided by a central 
reader and will include variables from qualitative and quantitative analyses of HRCT 
scans 
 
 Results of 
HRCT analyses will be provided by an external vendor in a data transfer and will not 
be entered in the EDC system 
 
3.4.3.1 
Qualitative HRCT Variables 
The qualitative HRCT variables will include central reader estimates of the extent of 
lung region abnormalities by lung (left and right) and region (upper, mid, and lower). 


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Possible values (as %) for each region will include “Absent”, “1-25”, “26-50”, “51-
75”, and “76-100”. Results for unreadable scans will be reported as “Unknown”. 
The central reader’s assessment of overall change in interstitial lung disease (ILD) 
from baseline to Visit 14 (or ET) will have possible values of “Much Better”, “Better”, 
“Same”, “Worse”, “Much Worse”, or “Unknown”. 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.4.3.2 
Quantitative HRCT Variables 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   


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3.4.5 Extent of Exposure 
Extent of exposure to study treatment will be summarized descriptively as: 
 
Duration of exposure (days) is calculated as: 
o (date of last dose – date of first dose) + 1 
 
Number and percentage of subjects who received the premedication 
 
Number of doses, total dose (mg) administered, and total infusion volume 
(mL) administered 
 
Number and percentage of subjects with any infusion interruptions, number of 
infusion interruptions per subject, total duration of infusion interruptions per 
subject, and reason for the infusion interruptions. 
Treatment compliance is calculated as: 


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 
Treatment compliance = 100 * total actual cumulative dose of administrated 
(mg) / total cumulative dose of the planned (mg) during the study. 
Where the cumulative dose of planned dose is defined as number of planned doses 
until last dose subject received multiplying by assigned dose (45 mg for low dose 
treatment arm and 90 mg for high dose treatment arm). The total planned dose is 
defined as the number of infusions planned until subject’s last dose (i.e. if subject’s 
last dose is at Week 22, then the subject’s expected number of infusions would be 
12).  
If date of first dose date is missing, then the randomization visit will be used. The 
last dose is the date of the last dose administered as of the data cut-off date. 
3.4.6 Adverse Events (AEs) 
All AEs recorded on the eCRF will be coded using the latest version of MedDRA 
dictionary, per the Data Management Plan, throughout the study and classified as 
either pre-treatment AEs or TEAEs as follows: 
 
Pre-treatment AEs are events that started prior to the first dose of any study 
treatment, including pre-medication. 
 
TEAEs are events that occur on or after the first dose of any study treatment 
including pre-medication through two weeks after the last dose of study 
treatment or adverse events which start before the first dose of study 
treatment, but increase in severity after the first dose through two weeks after 
the last dose of study treatment. 
Assessment of AE severity will be based on the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). The 
severity of all AEs is recorded as mild (Grade 1), moderate (Grade 2), severe (Grade 
3), life threatening consequences (Grade 4), or death (Grade 5), per CTCAE grading. 
If severity is missing for a TEAE, it will be considered severe only in the overall 
category in the summary tables. 
The relationship between an AE and study treatment is assessed as definite, 
probable, possible, unlikely, or none. A drug-related AE is an AE considered by the 
investigator as definitely, probably, possibly, or unlikely related to study treatment. 
If the relationship is unknown or missing, it is also considered as related to study 
treatment. 
AEs of special interest (AEOI) include 
 
 respiratory adverse events, and acute exacerbation of idiopathic 
pulmonary fibrosis. 


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3.4.7 Laboratory Evaluations 
The following hematology, serum chemistry, and urinalysis analytes recorded in the 
eCRF will be analyzed in this study. Absolute values will be compared to the 
laboratory reference range and classified as 
 
lower than reference range, clinically significant; 
 
lower than reference range, not clinically significant; 
 
normal in reference range; 
 
higher than reference range, not clinically significant; 
 
higher than reference range, clinically significant. 
All values classified as high or low will be flagged on the listings. The baseline value 
will be defined as last scheduled or unscheduled value prior to the first dose of study 
treatment. Assessments carried out on day of first study treatment administration 
are considered to have taken place before the drug administration, if the 
corresponding times have not been recorded. For post-baseline, only data from 
scheduled visits will be included in the summary tables. 


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Hematology 
Serum Chemistry 
Urinalysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.4.8 Vital Signs and Pulse Oximetry 
The following vital signs will be evaluated at the time points specified in study 
calendar. 
 
systolic and diastolic blood pressure (mmHg); 
 
heart rate (bpm); 
 
respiratory rate (breaths/min); 
 
oral temperature (°C). 
 
weight (kg) and height (cm). Height will be recorded only at first visit (visit 1a). 
 
SpO2 (%). 
The baseline value will be defined as last scheduled or unscheduled value collected 
prior to start of treatment. Assessments carried out on day of first study treatment 
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the corresponding times have not been recorded. For post-baseline, only data from 
scheduled visits will be included in the summary tables. 
3.4.9 Physical Examination 
Complete and abbreviated physical examinations will be evaluated in this study. A 
complete 
physical 
examination 
includes 
general 
appearance, 
eyes/ears/nose/throat/head/neck, chest and lungs (including inspection of the thorax 
for scars consistent with surgical lung biopsy at Screening), cardiovascular, abdomen, 
musculoskeletal, lymphatic, dermatologic, neurologic, psychiatric, and extremities. 
An abbreviated physical exam includes general appearance, nose/throat, jugular 
venous distension (sitting; absent or present), auscultation of the lungs 
(anterior/posterior, 4 quadrants; wheezes, crackles, rhonchi [absent or present], 
other sounds [describe]), auscultation of the heart, lower extremity venous distention 
(absent or present), pitting edema (0, 1+, 2+, 3+, or 4+). Any clinically significant 
abnormal result after baseline should be recorded as an AE. 
3.4.10 
12-Lead Electrocardiograms 
The following quantitative ECG measurements will be taken during the study: 
 
heart rate (bpm); 
 
RR interval (msec); 
 
PR interval (msec); 
 
QRS interval (msec); 
 
QT interval (msec); 
 
Fridericia’s corrected QT (QTcF) interval (msec). 
An overall investigator assessment of ECG will be provided (categories “normal”, 
“abnormal, not clinically significant” and “abnormal, clinically significant”). Clinically 
significant changes not already noted or significantly worsened than documented in 
Medical History will be recorded as AEs. 
The baseline value will be defined as last scheduled or unscheduled value collected 
prior to start of study treatment. Assessments carried out on day of first study 
treatment administration are considered to have taken place before the drug 
administration, if the corresponding times have not been recorded. For post-baseline, 
only data from scheduled visits will be included in the summary tables. When 
triplicate ECG tracings are obtained at a study visit or timepoint, the triplicate average 
(or if fewer, average of ECGs available) will be included in the analysis. 
3.4.11 
Other Safety Assessments 
The following other safety assessments will be performed: 


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5. 
Analysis populations 
5.1 Safety Population (SAF) 
The safety population (SAF) will include all subjects who receive at least 1 dose of 
study treatment. Subjects will be analyzed according to the study treatment they 
actually received. 
5.2 Intent-to-treat Population (ITT) 
The ITT population will include any randomized subjects with treatment assignment 
according to the planned randomization. 
5.3 Pharmacokinetic Population 1 (PK1) 
PK population 1 will include subjects in the PK subset who receive at least 1 dose of 
study treatment and have a majority of scheduled PK samples drawn for serial PK 
measurements that allow for PK parameters to be generated. A majority of samples 
is defined by sampling to at least 4 hours after end of infusion. Subjects who do not 
complete the study treatment infusion (Visit 2) will be excluded from the PK analysis. 
5.4 Pharmacokinetic Population 2 (PK2) 
PK population 2 will include subjects who have at least 3 of the 7 planned trough 
samples collected for subjects in the PK subset and both 2 planned trough samples 
collected for non-PK subjects to allow for a comparison of trough levels across dosing 
weeks. 
5.5 Per Protocol Population (PP) 
The per protocol population (PP) will exclude non-evaluable subjects and subjects 
with important protocol deviations thought to impact the ability to assess the effect 
of study treatment. 
Evaluable subjects are defined as subjects who received at least one dose of study 
treatment (not including pre-medication) and have baseline and at least one post 
baseline FVC or have baseline and at least one post baseline DLco. 
Non-evaluable subjects are subjects who do not meet the evaluable criteria. 
Protocol deviations are defined as any change, divergence, or departure from the 
study design or procedures defined in the study protocol. Important protocol 
deviations are a subset of protocol deviations that may significantly impact the 
correctness, accuracy, and/or completeness of the study data or that may 
significantly affect a subject’s rights, safety, or well-being. 


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6. 
Data Handling 
6.1 Time points and Visit Windows 
Day 1 is defined as the day of first dose of treatment (visit 2). Relative days after 
Day 1 are calculated as (assessment date – Day 1 date) + 1. Relative days prior to 
Day 1 are calculated as (assessment date – Day 1 date). The day prior to Day 1 is 
Day -1. 
All data will be analyzed using nominal study visits as defined in the Study Schedule 
of Assessment and eCRF. Data collected at unscheduled visits will be listed only, 
except for the following: 
 
Data from unscheduled visits will be included in the calculation of baseline 
laboratory values. 
 
Data from unscheduled visits will be included in the calculation of the worst 
CTCAE grade or abnormality used in the laboratory shift tables. 
 
For a nominal visit with a missing measurement, the measurements of the 
unscheduled visits occurring between this particular visit and the two 
adjacent visits will be used to assign the analysis value. The closest 
unscheduled visit value that is not assigned to previous visits will be assigned 
to this nominal visit. 
6.2 Handling of Dropouts, Missing Data, and Outliers 
Missing values on FVC, DLCO and DLCO corrected for hemoglobin, HRCT analysis 
variables, 
 at Visit 14 (Day 169) will not be imputed. In 
situations where the efficacy endpoints are missing, all available data will be analyzed 
with a mixed-effects model for repeated measures (MMRM). To evaluate robustness 
of results, sensitivity analyses will be performed by imputing missing data using 
statistical modelling of available data. 
Incomplete dates (partial or missing dates) for start date of AEs will be imputed and 
used to determine treatment-emergent status as follows: 
 
If the start date of an AE is completely missing, the first dosing date (Day 1) 
and time will be used for the imputation and the AE will be considered 
treatment-emergent. 
 
If the start date of an AE is missing day and month: 
o If the year of the AE start date is the year of the first dosing date, the 
month and day will be imputed using the month and day of first dosing 
date; 
o Otherwise, the month and day will be imputed as January 1. 
 
If the start date of an AE is missing the day only: 


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o If the year and month of the AE start date is the same as the year and 
month of the first dosing date, the day will be imputed using the day of first 
dosing date; 
o Otherwise, the day will be imputed as the first day of the month. 
 
If an imputed AE start date is later than the corresponding AE end date, the 
imputed AE start date will be replaced with the AE end date. 
AEs with missing relationship (related or not related) to study treatment will be 
treated as related AEs in summaries of AEs by relationship to study treatment. 
Partial dates with day or day and month missing for concomitant medications date 
will be imputed as follows: 
 
If the year and month are present and the day is missing, set the start date 
as the first day of the month, and set the end date as the last day of the month 
as applicable. 
 
If the year and day are present and the month is missing, set the month to 
January as the start date, and set month to December as the end month as 
applicable. 
 
If the year is present and the month and day are missing, set January 1 as the 
start date, and set December 31 as the end date as applicable. 
 
Completely missing dates will not be imputed. 
 
If the start date is completely missing and the end date is on or after the first 
dosing date, the medication will be classified as concomitant; if the end date 
is missing, the medication will be classified as ongoing. Medications for which 
both the start and end dates are missing will be classified as concomitant. 
7. 
Statistical Methods 
7.1 General Principles 
 
 
 
Efficacy data will be summarized and analyzed on the ITT population and PP 
population. Safety and treatment compliance data will be summarized based on the 
SAF population. Demography and other baseline characteristics data will be 
summarized based on the SAF population. 
Baseline is defined as the last scheduled or unscheduled value assessed on or before 
study day 1, prior to the first dose of study treatment, including pre-medication 
unless otherwise indicated. Assessments carried out on day of first dose 
administration are considered to have taken place before the dose administration, if 


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the corresponding times have not been recorded. Measurements that are obtained 
after the first date of study treatment will be considered post-baseline values. Change 
from baseline is defined as (post-baseline value – baseline value). 
Time-to-event endpoints will be summarized using Kaplan-Meier (KM) method to 
estimate the median, and the 25th and 75th percentiles. 
The following principles will be applied to all TFLs unless otherwise stated: 
Principle 
Value 
Treatment arm labels and 
order presented 
1. Placebo 
2. ND-L02-s0201 45 mg 
3. ND-L02-s0201 90 mg 
4. Total (if applicable) 
Tables 
Data in summary tables for safety will be 
presented by treatment arm, and Total, and visit 
(where applicable). Data in summary tables for 
efficacy will be presented by treatment arm. 
Listings 
All data collected presented by treatment arm, 
subject, and visit date (where applicable), unless 
otherwise specified.  
Descriptive summary 
statistics for continuous 
variables 
Number of subjects (n), mean, standard deviation, 
median, minimum, maximum  
Descriptive summary 
statistics for categorical 
variables 
Frequency counts and percentages [n (%)] 
Denominator for 
percentages 
By-visit summaries: number of subjects with non-
missing data at the visit assessed in the analysis 
population of each treatment arm; Other 
summaries: Number of subjects in the analysis 
population of each treatment arm, unless specified 
otherwise.  
Include “Missing” as 
category 
Included for demographics and other baseline 
characteristics when the number of missing is 
greater than zero for at least one treatment arm. 
Missing post-baseline values will not be 
summarized, unless otherwise specified.  
Display for percentage 
One decimal place, except for 100% 
Display for 0 percentages 
blank  
Display to one more decimal 
place than collected value 
Mean, Median 


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Principle 
Value 
Display to two more decimal 
places than collected value 
Standard Deviation 
Confidence interval 
Display to p-value 
P-values will be rounded to 3 decimal places. P-
values less than 0.0005 (e.g. 0.0002) will not be 
rounded to 3 decimal places (e.g. 0.000) but 
instead be displayed as <0.001.  
Date Format 
DDMMMYYYY 
Statistical Analysis 
All statistical tests will be conducted at the 2-sided, 
0.05 level of significance. There will be no 
adjustment for multiplicity. 
 
7.2 Subject Disposition and Data Sets Analyzed 
Subject disposition will be listed and summarized by treatment arm and overall for 
all randomized subjects and will include the number and percentage of subjects: 
 
randomized; 
 
randomized by randomization stratification factor (i.e., standard of care at 
enrollment); 
 
included in each analysis population (SAF, ITT, PK1, PK2, and PP). 
 
completed the study 
 
discontinued treatment 
 
primary reason for discontinuation of treatment 
 
terminated early from the study (terminated before Visit 8 or after visit 8) 
including early termination due to COVID-19 pandemic. 
 
primary reason for early termination. 
7.3 Protocol Deviations 
All protocol deviations will be listed. Important protocol deviations leading to 
exclusion from the PP population will be listed and summarized by treatment arm for 
the ITT population. Protocol deviations due to COVID-19 will be listed separately. 
The deviations leading to exclusion from the PP population will be identified before 
data are unblinded. 
7.4 Demographics and Other Baseline Characteristics 
Demographic and baseline characteristics will be listed and summarized by treatment 
arm and overall for the SAF population. Standard descriptive statistics will be 
presented for the continuous variables of: 
 
age (years) [as reported in the eCRF]; 


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 
weight (kg); 
 
height (cm); 
 
body mass index (kg/m2) [calculated as (weight/height2) where weight is in kg 
and height is in m];   
 
systolic blood pressure (mmHg); 
 
diastolic blood pressure (mmHg); 
 
body temperature (°C); 
 
pulse rate (beats/min); 
 
respiratory rate breaths (breaths/min); 
 
pulse oximetry (SPO2) (%); 
 
forced vital capacity (FVC) in L; 
 
percent predicted FVC (%); 
 
forced expiratory volume in 1 second (FEV1) in L; 
 
percent predicted FEV1 (%); 
 
ratio of FEV1/FVC; 
 
diffusion capacity of the lung for carbon monoxide (DLco) ; 
 
percent predicted DLco (%); 
 
hemoglobin corrected DLco; 
 
hemoglobin corrected percent predicted DLco (%); 
 
 
 
duration of IPF since diagnosis to start of study treatment (months) 
o calculated as (first dose date-initial IPF diagnosis date+1)/30.4375 
 
GAP IPF Risk of Mortality: The risk of mortality (1-, 2-, and 3-year risk) will be 
derived based on baseline data at the start of the treatment period using the 
Gender, Age, and Physiology (GAP) methodology described in Ley et al, 2012 
(Appendix 1); 
The total counts and percentages of subjects will be presented for the categorical 
variables of: 
 
gender;  
 
childbearing potential for females 
 
race; 
 
ethnicity; 
 
BMI group [Underweight (below 18.5); Normal (18.5 - 24.9); Overweight (25 
- 29.9); Obese (30 and above)] 
 
smoking history(yes/no) 
o If smoking history is yes, active smoker(yes/no) 
 
background standard of care (nintedanib, pirfenidone, none); 
 
 
 
 


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 
GAP IPF Stage: The IPF stage will be derived based on baseline data at the 
start of the treatment period using the Gender, Age, and Physiology (GAP) 
methodology described in Ley et al, 2012 (Appendix 1); 
No formal tests of statistical significance will be performed on the demographic and 
baseline data. 
7.4.1 Medical History 
Medical history will be coded using the lasted version of Medical Dictionary for 
Regulatory Activities (MedDRA), per the Data Management Plan, throughout the 
study. All medical history will be listed, and the number and percentage of subjects 
with any medical history will be summarized for the SAF population by system organ 
class (SOC) and preferred term (PT) for each treatment arm and overall. 
7.4.2 Previous and Concomitant Medications 
Medications including COVID-19 vaccination received prior to or concomitantly with 
study treatment will be coded using the lasted version of WHO Drug Dictionary 
Anatomical Therapeutic Chemical (ATC) Classification codes, per the Data 
Management Plan, throughout the study. Only medications taken within 14 days 
before Visit 1a through end of study will be included in summary table and listing. 
Prior medications and concomitant medications are defined as follows: 
 
Prior medications are those taken and ended within the interval from 14 days 
before Visit 1a up to the earliest of 24 hours before Visit 1a or date of informed 
consent. 
 
Concomitant medications are those taken on or after the earliest of 24 hours 
before Visit 1a or date of informed consent. Medication taken prior to but 
ongoing after the earliest of 24 hours before Visit 1a or date of informed 
consent will be considered concomitant medication. 
If 
a 
medication 
cannot 
be 
classified 
as 
“prior” 
or 
“concomitant” 
for 
missing/incomplete dates, it will be classified as both prior and concomitant. 
Prior medications and concomitant medications will be listed together and 
summarized separately for SAF populations for each treatment arm and overall. 
The number and percentage of patients using each medication will be displayed 
together with the number and percentage of patients using at least one medication 
within each therapeutic class (ATC-Level 2), chemical subgroup (ATC-Level 4), and 
preferred term. Tables will be sorted in descending overall frequency by ATC-Level 
2, ATC-Level 4, and preferred term, and then alphabetically. 


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7.5 Efficacy 
7.5.1 Primary Efficacy Analysis 
No primary efficacy endpoint is identified in the study protocol. Analyses of secondary 
endpoints for biological activity are described in Section 7.5.2. 
7.5.2 Secondary Efficacy Analysis 
7.5.2.1 
Analyses of FVC 
Values of FVC variables described in Section 3.4.1 will be summarized with descriptive 
statistics by treatment arm and visit for the ITT Population. The summary will include 
FVC (or percent predicted FVC) values, the change and percentage change from 
baseline to each post-baseline visit for each parameter. Results from unscheduled 
visits will not be included in summary tables, but will be included in subject-level 
listings and statistical model. 
A random coefficients model will be used to analyze the rate of decline in FVC (L) 
from baseline to Visit 14 (Day 169) as well as the absolute change from baseline in 
FVC at Visit 14 in the ITT Population. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Reporting of model results will include the estimated mean change from baseline, 
adjusted for baseline FVC and standard of care, at each timepoint 
 
with corresponding 95% CIs. In addition, mean slope (rates of 
change) of FVC from baseline to Visit 14 (Week 24) for each treatment arm will be 
estimated along with 95%CIs.  Treatment differences between mean slopes and 
corresponding p-values will be presented. No adjustments for multiple comparisons 
will be made. Spaghetti plots of individual FVC (L) data over time will be produced 
for each treatment arm with estimated means from the random coefficient model and 
95% CIs at each timepoint 
 superimposed.   
Similar analysis will be repeated for FVC (L) relative change from baseline, absolute 
and relative change from baseline for percent predicted FVC (%FVC). 


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Study treatment response is defined as a decline in FVC (L and % of predicted) of no 
more than 10% in the relative change at Visit 14 that is calculated as: 
𝐶ℎ𝑎𝑛𝑔𝑒 𝑖𝑛 𝐹𝑉𝐶 𝐿 (%) = (𝐹𝑉𝐶 𝐿 𝑎𝑡 𝑉𝑖𝑠𝑖𝑡 14 − 𝐹𝑉𝐶 𝐿 𝑎𝑡 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒)
𝐹𝑉𝐶 𝐿 𝑎𝑡 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒
∗100% 
The change in FVC % of predicted (%) will be calculated as: 
𝐶ℎ𝑎𝑛𝑔𝑒 𝑖𝑛 𝐹𝑉𝐶 % 𝑜𝑓 𝑝𝑟𝑒𝑑𝑖𝑐𝑡𝑒𝑑 (%) =  
(𝐹𝑉𝐶 % 𝑜𝑓 𝑝𝑟𝑒𝑑𝑖𝑐𝑡𝑒𝑑 𝑎𝑡 𝑉𝑖𝑠𝑖𝑡 14 − 𝐹𝑉𝐶 % 𝑜𝑓 𝑝𝑟𝑒𝑑𝑖𝑐𝑡𝑒𝑑 𝑎𝑡 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒)
𝐹𝑉𝐶 % 𝑜𝑓 𝑝𝑟𝑒𝑑𝑖𝑐𝑡𝑒𝑑 𝑎𝑡 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒
∗100% 
A positive value indicates improvement. Number and percent of subjects responding 
to treatment will be summarized. 
The number and percent of subjects within each treatment arm showing an 
improvement, and subjects showing a decline of 0% to ≤5%, >5% to ≤10%, and 
>10% at Visit 14 (day 169) will be summarized by treatment arm. Subjects with an 
FVC response is defined as improvement in FVC or a decline of ≤10% from baseline 
FVC value. 
7.5.2.2 
Analyses of DLco 
Values of DLco variables described in Section 3.4.2 will be summarized with 
descriptive statistics by treatment arm and visit for the ITT Population. The summary 
will include the absolute and percent change from baseline to each post-baseline visit 
for each parameter. Results from unscheduled visits will not be included in summary 
tables or statistical models, but will be included in subject-level listings. 
DLco corrected for hemoglobin and DLco not corrected for hemoglobin will be 
analyzed similarly as FVC as described in section 7.5.2.1. 
7.5.2.3 
Analyses of HRCT 
Values of HRCT variables described in Section 3.4.3 will be summarized with 
descriptive statistics by treatment arm and visit for the ITT Population. The summary 
will include the change from baseline to Visit 14 (or ET) for each parameter. Results 
from unscheduled visits will not be included in summary tables or statistical models, 
but will be included in subject-level listings. In addition, subjects who have visit 14 
assessment and subjects who withdraw from treatment before visit 14 and have only 
ET assessment will be summarized separately for each HRCT variable.  
The qualitative overall change in ILD from baseline to Visit 14/ET will be analyzed 
using the Kruskal-Wallis (KW) test. The test statistic and p-value from the KW test 
will be reported along with the pairwise comparisons of each active treatment arm 
with placebo. 


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A random coefficients model will be used to analyze the rate of change in the 
quantitative QLF score from baseline to Visit 14 as well as the absolute change from 
baseline at Visit 14. The model will include QLF score as the dependent variable, 
background standard of care, treatment, time and the interaction of treatment*time 
and baseline QLF score as fixed effects, and subject and subject*time as random 
effects. Subjects with missing values at Visit 14 will not be imputed for the analysis. 
The unstructured covariance model (UN) will be used to estimate the variance and 
covariance of random slopes and intercepts. If the computational algorithm fails to 
converge, the variance components (VC) covariance structure will be used for the 
analysis.  
Reporting of model results will include the estimated mean change from baseline, 
adjusted for baseline QLF and standard of care, at Visit 14 with corresponding 95% 
CIs for each treatment arm. In addition, mean slope (rate of change) of QLF from 
baseline to Visit 14 for each treatment arm will be estimated along with 95% CIs. 
Treatment differences between mean slope and corresponding p-values will be 
presented. No adjustments for multiple comparisons will be made. The analysis will 
be repeated for subjects who have visit 14 assessment and subjects who withdraw 
from treatment before visit 14 and have only ET assessment. Spaghetti plots of 
individual QLF data over time will be produced for each treatment arm with estimated 
means from the random coefficient model and 95% CIs at Visit 14 superimposed.   
Similar analysis will be repeated for relative change of QLF from baseline (derived as 
100*(QLF score at Visit 14/ET-Baseline QLF score)/Baseline QLF score).  
Other quantitative HRCT variables including ground glass opacity, reticulation, 
honeycombing, normal lung, and emphysema will be analyzed similarly as QLF score. 
7.5.2.4 
Analysis of Time to First IPF Exacerbation or Death 
Time to first IPF exacerbation or death is defined as the time from start of study 
treatment to first acute exacerbation of IPF which is determined by the investigator 
(Adverse event CRF, AE preferred term equal to Idiopathic pulmonary fibrosis) or 
death for each subject. Subjects who do not experience acute exacerbation of IPF will 
be censored to the last known alive date. 
The analysis of time to first IPF exacerbation or death of each active treatment arm 
versus placebo will be performed using a log-rank test stratified with standard of care 
to generate p-value for each comparison. Median time to first IPF exacerbation and 
corresponding 95% CI as well as proportion of subjects without the event at 8-week 
interval will be summarized for each treatment arm using the Kaplan-Meier (KM) 
analysis. KM plot of time to first IPF exacerbation will also be presented by treatment. 
In addition, the hazard ratio and 95% CI will be calculated from a stratified Cox 
proportional hazards model that includes standard of care as the strata.  


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The rate of acute IPF exacerbation, which is defined as the number of patients with 
any acute IPF exacerbation divided by the total study duration (years) summed over 
patients in that treatment arm and then multiplied by 100 to present in terms of per 
100 patient years, will be summarized by treatment arm. Tests of differences in rates 
between treatment arms will be assessed using chi-squared tests (χ2) at the 2-sided, 
0.05 level of significance. Corresponding exact 95% CIs of study treatment 
proportions and respective active ND-L02-s0201 differences from placebo will be 
estimated.  
7.5.2.5 
Other Secondary Analyses 
The rates of hospitalization for respiratory ailments, which is defined as the number 
of patients with any hospitalization for respiratory ailments divided by the total study 
duration (years) summed over patients in that treatment arm and then multiplied by 
100 to present in terms of per 100 patient years, will be tabulated by treatment arm. 
Tests of differences in event rate will be assessed using chi-squared tests (χ2) at the 
2-sided, 0.05 level of significance. Corresponding exact 95% CIs of study treatment 
proportions and respective active ND-L02-s0201 differences from placebo will be 
estimated. Time to hospitalization for respiratory ailments or death is defined as the 
time from start of study treatment to hospitalization for respiratory ailments or death 
for each subject. Subjects who do not experience hospitalization for respiratory 
ailments and have not died will be censored to last known alive date. The analysis of 
time to hospitalization for respiratory ailments or death of each active treatment arm 
versus placebo will be performed using a log-rank test stratified with standard of care 
to generate p-value for each comparison. Median time to hospitalization for 
respiratory ailments or death and corresponding 95% CI as well as proportion of 
subjects without the event at the 8- week interval will be summarized for each 
treatment arm using the Kaplan-Meier (KM) analysis. KM plot of time to 
hospitalization for respiratory ailments or death will also be presented by treatment. 
The hazard ratio and 95% CI will be calculated from a stratified Cox proportional 
hazards model that including standard of care as the strata.   
Rate of mortality due to any cause, which is defined as the number of patients who 
died due to any cause, divided by the total study duration (years) summed over 
patients in that treatment arm and then multiplied by 100 to present in terms of per 
100 patient years, will be analyzed similarly as the rate of hospitalization for 
respiratory ailments. In addition, overall survival which is defined as the time from 
start of study treatment to death due to any cause will be analyzed similarly as time 
to hospitalization for respiratory ailments. Any patient not known to have died at the 
time of analysis will be censored to the last known alive date. 
Rate of deterioration of IPF resulting in lung transplantation (up to 12 weeks after 
the end of study treatment) or death, which is defined as the number of patients with 


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any deterioration of IPF resulting in lung transplantation divided by the total study 
duration (years) summed over patients in that treatment arm and then multiplied by 
100 to present in terms of per 100 patient years, will be analyzed similarly as the 
rate of hospitalization for respiratory ailments. In addition, time to deterioration of 
IPF resulting in lung transplantation or death defined as the time from start of study 
treatment to deterioration of IPF resulting in lung transplantation (up to 12 weeks 
after the end of study treatment) or death will be analyzed similarly as time to 
hospitalization for respiratory ailments. Any patient not known to have IPF resulting 
in lung transplantation (up to 12 weeks after the end of study treatment) or death at 
the time of analysis will be censored to 12 weeks after the end of study treatment or 
the last known alive date, whichever is earlier. 
7.5.3 Sensitivity Analysis 
 
Multiple imputation assuming missing not at random (MNAR) 
Sensitivity analysis will be performed for secondary efficacy endpoints including 
change and percent change from baseline in FVC (L) and percent predicted FVC 
(%), change from baseline in DLco corrected for hemoglobin and DLco not 
corrected for hemoglobin, and change and percent change from baseline in 
quantitative HRCT variables using multiple imputations with missing data imputed 
prior to fitting the linear regression. An assumption of MNAR will be made based 
upon an approach using regression based multiple imputations with missing data 
for all subjects imputed from a regression model estimated from patients in the 
placebo arm who stay on until visit 14. SAS PROC MI and MIANALYZE will be used 
to generate 100 complete datasets and combine the results from each complete 
dataset analyzed using ANCOVA model with baseline value, treatment arm, and 
standard of care as covariates. 
 
Excluding subjects with deviations 
All the secondary efficacy analysis described in section 7.5.2 will be repeated using 
the PP population. 
7.5.4 Subgroup Analysis 
Subgroup analysis will be conducted comparing both active treatment arms with 
placebo arm to assess consistency of treatment effects across potential prognostic 
factors. 
The following subgroups of ITT population will be analyzed for the secondary efficacy 
endpoints: 
 
Standard of care (none vs. nintedanib vs. pirfenidone) 
 
Anti-fibrosis (none vs. nintedanib or pirfenidone) 


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 
BMI (<30 vs. ≥30) 
 
GAP IPF Stage (I vs. II vs. III) 
 
Duration of IPF since diagnosis to start of study treatment (≤1 vs. 1<-2 vs. 2<-3 
vs. 3<-4 vs. ≥4 year) 
 
Subjects who adhere to the protocol schedule vs. subjects who missed at least 
one treatment but continued treatment after the interruption vs. early terminated 
subjects (subjects did not miss any treatment before early termination)  
 
COVID-19 vaccination (not vaccinated vs. vaccinated prior to treatment start vs. 
vaccinated while on treatment) 
More subgroup analysis may be done ad-hoc given feasible data support. 
No adjustment to the significance level for testing will be made. For each subgroup 
level, the analysis will be as described in 7.5.2 except for subgroup analysis of 
standard of care, the standard of care covariate will be removed from the analysis 
model.  
If there are less than 10 subjects across both treatment arms in comparison in a 
subcategory then only descriptive summaries will be provided.  
Forest plots will be provided for the secondary efficacy analysis. For rate of decline 
in FVC (L) or FVC (%FVC) from baseline to Visit 14, the estimated mean slope 
difference and 95% CI will be summarized and presented on the forest plot for each 
subgroup category as well as the overall ITT population. For change from baseline in 
FVC (L), percent predicted FVC (%FVC), DLco corrected for hemoglobin, DLco not 
corrected for hemoglobin, and quantitative HRCT variables (as described in 3.4.3), 
estimated means difference and 95% CI will be summarized and presented on the 
forest plot for each subgroup category as well as the overall ITT population. If the 
model does not converge then only descriptive summaries will be presented.  
For time to event analysis described in section 7.5.2.4 and 7.5.2.5, for each subgroup 
level of a factor, the hazard ratio (HR) and 95% CI will be calculated from a Cox 
proportional hazards model that includes treatment and presented on a forest plot. 
If there are too few events available for a meaningful analysis of a particular subgroup 
(less than 10 events across both treatment arms in comparison in a subcategory), 
the HR and 95% CI will not be created for the subgroup and only descriptive 
summaries (number of event and proportion of subjects with events) will be provided.  
 
 
 
 
 


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7.5.5.2 
 Other analyses 
Analyses to compare treatment effect between the two active treatment arms may 
be conducted ad hoc if both low dose and high dose treatment arm shows 
significant results versus the placebo arm. 
7.6 Safety  
7.6.1 Extent of Exposure 
Duration of exposure will be summarized descriptively as a continuous variable in 
days, and also in the following categories: 
 
0 - <2 weeks (14 days); 
 
2 - <4 weeks (28 days); 
 
4 - <6 weeks (42 days); 
 
…; 
 
20 - ≤23 weeks (161 days) 
 
The number and percent of subjects who received the premedication will be 
summarized by visit and overall and treatment arm. The volume and dosage for study 
treatment infusion will be summarized descriptively by visit or overall and treatment 
arm. 
The number and percent of subjects who have at least 1 infusion interruption, and 
number and percent of subject who have at least 1 infusion interruption not resumed 
at any visit as documented in the eCRF will be summarized by visit or overall and 
treatment arm. 
The number of infusion interruptions per subject will be summarized both as a 
continuous variable using descriptive statistics, and as a categorical variable 
(categories: 0, 1, and ≥2) by visit or overall and treatment arm. Reasons for the 
infusion interruptions will also be presented. A reason that was recorded multiple 
times at different visits for one subject will be counted once for this subject for overall 
summary. In addition, the number of subjects who have at least 1 infusion 
interruption resumed at any visit, and the duration of such interruptions will be 
summarized. A listing will be provided for subjects with any infusion interruptions. 


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Treatment compliance will be summarized descriptively by treatment arm for the SAF 
population. The following percentage compliance categories will also be summarized: 
 
<60% 
 
60 – 79% 
 
80 – 100% 
 
>100% 
Subjects who missed 1 or 2 doses of study treatment due to COVID-19 pandemic 
as permitted by protocol will be summarized separately for exposure duration, total 
number of doses, and treatment compliance. A swimmer plot will be created for all 
scheduled study treatment administration from Day 1 to end of study. Events of IP 
administration, skipping study treatment due to COVID-19 pandemic, or treatment 
termination will be included. 
7.6.2 Adverse Events 
All AE data will be listed. Treatment-emergence status will be flagged in the listing. 
In addition, corresponding listings of serious AEs (SAEs), AEs resulting in death, 
TEAEs leading to discontinuation of study treatment, and TEAEs of special interests 
will be produced. 
An overview table will summarize the number of all TEAEs, the number and 
percentage of subjects with at least one of the following TEAEs, by standard of care 
(none, nintedanib, pirfenidone), treatment arm and overall, where subjects with 
more than one TEAE in a particular category are counted only once in that category: 
 
any TEAE; 
 
any TEAE by relationship (definite, probable, possible, unlikely, none); 
 
drug-related TEAE; 
 
any TEAE by severity (mild, moderate, severe, life-threatening consequences, 
death); 
 
TEAE leading to study treatment interrupted; 
 
TEAE leading to study treatment withdrawn; 
 
TEAE leading to discontinuation from the study; 
 
Treatment-emergent SAEs; 
 
drug-related SAE; 
 
AEOIs 
 
Each AEOIs 
 
 
 
 
o Respiratory adverse events 
o Acute exacerbation of idiopathic pulmonary fibrosis 
 
TEAE leading to death; 


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This summary table will be repeated for each of the following COVID-19 vaccination 
status: 
 
Subjects vaccinated prior to start of study treatment 
 
Subjects vaccinated while on treatment 
 
Subjects not vaccinated 
 
The number and percentage of subjects reporting each TEAE will be summarized by 
System Organ Class (SOC) and Preferred Term (PT) by treatment arm and overall 
for the SAF population. Tables will be sorted alphabetically by SOC. PTs will be sorted 
by descending overall total. The following summaries will be produced: 
 
TEAEs, by SOC and PT; 
 
TEAEs by PT; this table will also be repeated for each COVID-19 vaccination 
status as described above; 
 
TEAEs with frequency >10% in one or more treatment arms by PT; 
 
TEAEs related to the study treatment, by SOC and PT; 
 
TEAEs related to the study treatment, by PT; 
 
TEAEs by relationship to the study treatment, by SOC and PT; 
 
TEAEs related to pre-medication, by SOC and PT; 
 
TEAEs by maximum severity and PT; 
 
TEAEs related to the study treatment by maximum severity and PT; 
 
TEAEs leading to the study treatment interruption, by SOC and PT; 
 
TEAEs leading to the study treatment withdrawn, by SOC and PT; 
 
TEAEs related to the study treatment leading to the study treatment 
withdrawn, by SOC and PT; 
 
Serious TEAEs, by SOC and PT; 
 
Serious TEAEs related to the study treatment, by SOC and PT; 
 
Serious TEAEs with frequency >5% in one or more treatment arm by PT; 
 
In the above summaries, subjects with more than one AE within a particular SOC are 
counted only once for that SOC. Similarly, subjects with more than one AE within a 
particular PT are counted only once for that PT. For summaries by maximum severity, 
subjects with multiple AEs within a particular SOC or PT will be counted under the 
category of their most severe AE within that SOC or PT. AEs with missing severity 
will be included as severe in the overall count of subjects with AEs, but will not be 
included in the counts of subjects with AEs within a SOC or PT. 
The number and percentage of subjects with at least 1 treatment-emergent AEOI, 
and each type of treatment-emergent AEOI will be summarized. The number and 
percentage of subjects reporting at least 1 treatment-emergent AEOI will be 
summarized by SOC and PT for the following in the SAF population: 


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 
treatment-emergent AEOI by SOC and PT; 
 
serious treatment-emergent AEOI by SOC and PT; 
 
treatment-emergent AEOI leading to study treatment interruption by SOC and 
PT; 
 
treatment-emergent AEOI leading to study treatment withdrawn by SOC and 
PT. 
 
 
 
 
 
 
 
 
 
No statistical comparisons of AEs between treatment arms will be performed. 
7.6.3 Laboratory Evaluations 
All laboratory data will be reported in conventional units. Reference range will be 
presented in the listing. Out-of-reference-range values will be flagged as high (H) or 
low (L) in the listings. 
Laboratory data will be summarized by treatment arm, overall, and visit using 
standard descriptive statistics for the SAF population. Changes from baseline will also 
be summarized. 
For hematology and serum chemistry, shift tables presenting movement in and out 
of reference range from baseline to each scheduled post-baseline visit will be 
provided for each treatment arm. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
For subjects with abnormal baseline values, the following summary will also be 
created: 


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 
ALT or AST >2x Baseline or total bilirubin >1.5x Baseline 
 
ALT or AST >2x Baseline and a concomitant total bilirubin >2x Baseline 
 
If baseline measurements were <2.5x ULN: ALT or AST >5x baseline 
For all subjects, number of subjects with elevated ALT or AST and Total Bilirubin 
following the Hy’s Law (ALT or AST >3X ULN and Total Bilirubin >2X ULN) will be 
summarized. The onset date of ALT or AST elevation should be prior to or on the date 
of Total Bilirubin elevation. Additionally, Evaluation of Drug Induced Serious 
Hepatotoxicity (eDISH) plots will be generated for peak total bilirubin vs peak ALT 
and peak AST. 
Box-plots of the absolute value of lab tests at each scheduled visit will be provided. 
All lab tests results will also be listed. 
7.6.4 Vital Signs and Pulse Oximetry 
Vital signs and SpO2 data and changes from baseline in vital signs and SpO2 will be 
summarized by visit using standard descriptive statistics for the SAF population. For 
visits that have vital sign data collected before, during, and after study treatment 
infusion, the pre-infusion vital sign will be included in the summary table. A table for 
change from pre-infusion will also be provided for the visits with multiple vital sign 
measurements before, during, and after study treatment infusion. Vital sign findings 
per subject will be detailed in a listing. 
7.6.5 Electrocardiograms 
The ECG measurements and changes from baseline in ECG will be listed and 
summarized by treatment arm and visit using standard descriptive statistics for the 
SAF population. For visits (visit 4 and visit 8) where both pre-infusion and post-
infusion ECG are measured, the pre-infusion ECG will be included in the summary 
table of change from baseline. In addition, difference of ECG measurements between 
pre-infusion and post-infusion of study treatment for visit 4 and visit 8 will be listed 
and summarized. 
The number and percent of subjects with the averaged QT interval (msec) and 
Fridericia’s corrected QT (QTcF) interval (msec) meeting below criteria will be 
summarized by treatment arm for baseline and post-baseline visits: 
 
QT interval >450 msec; 
 
QT interval >480 msec; 
 
QT interval >500 msec; 
 
QTcF interval >450 msec; 
 
QTcF interval >480 msec; 
 
QTcF interval >500 msec. 


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In addition, the number and percentage of subjects with average QT or QTcF interval 
meeting the following criteria will be summarized by treatment arm for each post-
baseline visit: 
 
change from baseline in QT interval >30 msec; 
 
change from baseline in QT interval >60 msec; 
 
change from baseline in QTcF interval >30 msec; 
 
change from baseline in QTcF interval >60 msec. 
ECG overall interpretation (normal, abnormal not clinically significant and abnormal 
clinically significant) will be presented as a categorical summary by treatment arm 
and scheduled visit. The ECG measurements and changes from baseline in ECG Shifts 
from baseline (normal vs. abnormal, not clinically significant vs. abnormal, clinically 
significant) at each post-baseline visit will be presented. 
7.6.6 Physical Examination 
Physical examination results (normal/abnormal) will be summarized for each visit 
by treatment arm. Details of abnormalities will be listed for each subject. 
7.6.7 Other Safety Analyses 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
Serology tests of HIV, HIV-1 RNA, hepatitis B, and hepatitis C as well as SARS-
COV-2 will be listed.  


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7.6.9 Impact of COVID-19 Pandemic 
The impact of COVID-19 pandemic on subject participation in the study will be 
summarized by treatment arm (including a total column) and visit with the number 
and percentage of subjects whose planned study visit was not performed, partially 
performed, performed by telephone visit, or performed outside of the protocol-
specified window. In addition, a summary of subjects who early terminated study 
treatment or the study due to COVID-19 also will be provided. The subject-level 
listing will be provided and it will include any alternative procedures used to collect 
data per the eCRF. 
Listing of protocol deviations due to COVID-19 will also be provided. 
7.7 Interim Analysis 
No formal interim analyses are planned for this study. 
8. 
Changes in Planned Analysis 
The following changes from protocol specified statistical analyses are made in this 
SAP. 
Section 3.2 and 7.5.2.4 The efficacy endpoint Time to first acute IPF exacerbation 
has been updated to Time to first acute IPF exacerbation and death to avoid 
dependent censoring.   
Section 7.5.2.1, 7.5.2.2, 7.5.2.3, and 7.5.5 Analysis of change from baseline in 
FVC, DLco, HRCT QLF, 
 will be using random 
coefficient model instead of ANCOVA. The random coefficient model will handle 
missing data by making use of all available data include subjects with missing data 
and no missing value will be imputed. 
Section 7.5.3 Sensitivity analysis of FVC will use multiple imputation instead of 
ANCOVA without missing value imputation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Appendices 
Appendix 1: GAP Algorithm for IPF Stage and Predicted 
Mortality  
GAP IPF stage for each subject will be derived by summing the points in each of the 
following categories for each randomized subject: 
Gender 
Points 
Male 
0 
Female 
1 
Age 
 
≤60 
0 
61-65 
1 
>65 
2 
Baseline FVC, % Predicted 
 
>75 
0 
50-75 
1 
<50 
2 
Baseline DLco*, % Predicted 
 
>55 
0 
36-55 
1 
≤35 
2 
Not Performed 
3 
*Corrected for hemoglobin 
IPF stage for each subject will be assigned based on the total points as follows: 
Sum of Points 
IPF Stage 
0-3 
I 
4-5 
II 
6-8 
II 
 
Risk of mortality will be derived using the following algorithm: 
Step 1: Calculate S 
S = [0.337 (GENDER) – 0.015 (FVC – 68.464) + 0.092 (AGE1 – 67.676) – 0.052 
(AGE2) + 2.237 (DLco1) + 0.024 (DLco2)] x 0.909 
Where: 


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1) GENDER = 
a. 0.293 if the patient is male 
b. –0.707 if the patient is female 
2) FVC = FVC, % predicted at baseline 
3) AGE1 = patient’s age (years) 
4) AGE2 = refer to the table below. Enter the value of AGE2 that corresponds to the 
patient’s age. 
AGE 
AGE2 
AGE 
AGE2 
AGE 
AGE2 
AGE 
AGE2 
≤50 
0 
60 
0.236 
70 
6.345 
80 
22.043 
51 
0 
61 
0.408 
71 
7.625 
81 
23.739 
52 
0 
62 
0.648 
72 
9.009 
82 
25.435 
53 
0 
63 
0.968 
73 
10.481 
83 
27.130 
54 
0 
64 
1.378 
74 
12.027 
84 
28.826 
55 
0 
65 
1.890 
75 
13.632 
85 
30.522 
56 
0.002 
66 
2.516 
76 
15.280 
86 
32.217 
57 
0.015 
67 
3.266 
77 
16.959 
87 
33.913 
58 
0.051 
68 
4.153 
78 
18.652 
88 
35.609 
59 
0.121 
69 
5.183 
79 
20.348 
89 
37.304 
 
5) DLco1 = 
a. 0.921 if the subject could not do the DLco test 
b. –0.079 if the subject could do the DLco test 
6) DLco2 = 
a. –50.549 if the subject could not do the DLco test 
b. (49.451 – the subject’s baseline DLco, % predicted) if the subject could do the 
test 
Step 2: Calculate risk using S: 
1-year risk = 100 x [1 – exp(–exp (S) x 0.225)] 
2-year risk = 100 x [1 – exp(–exp (S) x 0.486)] 
3-year risk = 100 x [1 – exp(–exp (S) x 0.768)] 


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Appendix 2:  Schedule of visits 
 
 Screeninga 
Treatment Period 
EOT 
Follow-Up 
Visit 
1a 
1b 
2 
3 
4 
5, 7, 9, 11, 13 
(Simple tests) 
6, 8, 10, 12  
(Detailed 
tests) 
14 (or ET) 
15 
16 
Week 
-6 to -1 
0 
2 
4 
6, 10, 14, 18, 
22 
8, 12, 16, 
20 
24  
(2 wk 
postdose) 
28  
(4 wk post 
V14/ET) 
34  
(10 wk 
post 
V14/ET) 
Study Day -42 to -7 
1 2 15 29 
43, 71, 99, 
127, 155 
57, 85, 
113, 141 
169 
197 
239 
Allowable Window (days)b 
 
 
 
± 
4 
± 
7 
± 7 
± 7 
± 7 
± 7 
± 7 
Study Procedure 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
Xc 
 
 
 
 
 
 
 
 
 
 
Eligibility  
X 
X 
X 
 
 
 
 
 
 
 
 
Demographics and baseline 
characteristics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Adverse events 
Xd 
X 
X Xe X X 
X 
X 
X 
X 
X 
IPF history and previous 
treatments 
X 
 
 
 
 
 
 
 
 
 
 
Prior medications  
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medications  
Xd 
X 
X Xe X X 
X 
X 
X 
X 
X 
Physical examination 
(complete) 
X 
 
 
 
 
 
 
 
X 
 
 
Physical examination 
(abbreviated)f 
 
X 
X 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
 
X 
 
 
12-lead ECG 
X 
X 
 
 
 
Xg 
 
 
X 
 
 
Vital signsh 
X 
X 
X 
 
X X 
X 
X 
X 
X 
X 
Chemistry 
X 
 
X 
 
X X 
 
X 
X 
 
X 
Hematology 
X 
Xn X 
 
 
X 
 
X 
X 
Xn 
X 
Urinalysis  
X 
 
 
 
 
 
 
 
X 
 
X 
Pregnancy test (urine) for 
WCBPo 
X 
 
X 
 
 
X 
 
X 
X 
X 
X 
Serology (HCV Ab, HBsAg, 
HIV 1/2) 
X 
 
 
 
 
 
 
 
 
 
 
SARS-CoV-2 testr 
X 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 


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 Screeninga 
Treatment Period 
EOT 
Follow-Up 
Visit 
1a 
1b 
2 
3 
4 
5, 7, 9, 11, 13 
(Simple tests) 
6, 8, 10, 12  
(Detailed 
tests) 
14 (or ET) 
15 
16 
Week 
-6 to -1 
0 
2 
4 
6, 10, 14, 18, 
22 
8, 12, 16, 
20 
24  
(2 wk 
postdose) 
28  
(4 wk post 
V14/ET) 
34  
(10 wk 
post 
V14/ET) 
Study Day -42 to -7 
1 2 15 29 
43, 71, 99, 
127, 155 
57, 85, 
113, 141 
169 
197 
239 
Allowable Window (days)b 
 
 
 
± 
4 
± 
7 
± 7 
± 7 
± 7 
± 7 
± 7 
Premedication (optional)w 
 
 
X 
 
X X 
X 
X 
 
 
 
Study treatment 
 
 
X 
 
X X 
X 
X 
 
 
 
Abbreviations: 
 COVID-19 = coronavirus disease; 
 
 ECG = electrocardiogram; EOT = end-of-treatment; ET = Early Termination; 
 HBsAg = 
hepatitis B surface antigen; HCV Ab = hepatitis C virus antibody; HIV 1/2 = human immunodeficiency virus type 1 or 2; 
 
ICF = informed consent form; IPF = idiopathic pulmonary fibrosis; 
 
 
 QC = quality control; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; 
; SOC = standard of care; 
 
; V = Visit; WCBP = women of childbearing potential; 
 
 
Note: Refer to Section 18.6 of the protocol for guidance on clinical trial conduct relating to COVID-19. 
a Screening begins with the first Visit 1a procedure (excluding signing the ICF) and may be shorter than 42 days. If possible, 
plan Visit 1b and schedule the 
at the time of Visit 1a. To assure that an ineligible subject does not undergo an 
unnecessary 
 ALL Visit 1a procedures MUST be completed before any Visit 1b procedures may be started. 
 
 
 
 
 
b Subjects should be dosed on the study day listed in the Study Schedule (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13), 
ensuring a minimum of 7 days between each dose. Assessments not associated with study treatment infusion may be performed 
on days other than the dosing day for scheduling purposes, as long as they are performed before the infusion. 
c The ICF should be signed before Visit 1a to allow the site to instruct the subject to withhold bronchodilator use as required for 
the Visit 1a PFT (see Section 11.2.2 of the protocol) 
 
 
d Adverse event and concomitant medication collection will begin 24 hours before Visit 1a. 
e On Day 2, study personnel will call subjects not returning to the site to collect any AEs and concomitant medications that may 
have occurred after leaving the site on Day 1. 
f Other abbreviated physical examinations may be performed at the discretion of the Investigator on the basis of signs or 
symptoms. See Section 11.1.3 for more information. 
g During Visit 4 (Day 29), ECGs will be performed once, within 30 minutes after the end of the study treatment infusion. 


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h Vital signs and SpO2 will be measured at every study visit, except at Visit 2 (Days 2 and 3; subjects participating in the PK 
substudy will only have vital signs measured). On dosing days vital signs and SpO2 will be measured thrice: once before the 
study treatment infusion (if premedication is administered, vital signs should be measured after premedication), midinfusion ± 
5 minutes 
 
 and within 15 minutes after the end of the study treatment infusion. The frequency 
of monitoring vital signs may be increased as warranted by clinical management. See Section 11.1.4 and Section 11.2.1 of the 
protocol for more information.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
o A positive urine pregnancy test will be followed up with a serum pregnancy test. 
 
 
 
 
 
r Every effort should be made to test for SARS-CoV-2 virus or viral antigen at Visit 1a if testing is available. The test used 
should have regulatory approval for marketing and sample collection should be performed per the assay’s specifications. 
Depending on the site and its location, options for subject testing may vary. Refer to Section 8.3.3 of the protocol for guidance 
on SARS-CoV-2 testing. 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
w Subjects may be premedicated to mitigate the risk of infusion-related reactions at the discretion of the Investigator 
(see Section 18.5 of the protocol). 


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Appendix 3:  FVC and %FVC Baseline Determination 
The baseline for FVC and %FVC will be determined as per the 
 
Specification.   
 
 
 
































































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Appendix 4:  HRCT Assessment 
The qualitative and quantitative HRCT assessments are included in the 
 
Independent Review Charter V 3.0.