Clinical trial NCT04419558
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic Pulmonary Fibrosis IPF Idiopathic Interstitial Pneumonia Interstitial Lung Disease Lung Fibrosis
Sponsor: FibroGen
Start date: 2020-09-30; Completion date: 2023-09-04
Enrollment: 372 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 3 trial to evaluate the efficacy and safety of 30 milligrams (mg)/kilogram (kg) intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in participants with Idiopathic Pulmonary Fibrosis (IPF). There is a 48-week randomized treatment phase followed by an optional, open-label extension phase.

Detailed description:
The intent of this study is to evaluate the efficacy and safety of pamrevlumab as monotherapy in participants with IPF. Participants who are not being treated with approved IPF therapies (that is, nintedanib or pirfenidone) may be eligible for screening. Examples of reasons participants may not be treated with approved IPF therapies include but are not limited to:

* Intolerant or not responsive to approved IPF therapies
* Ineligible to receive these therapies
* Participant voluntarily declines to receive approved IPF therapies after being fully informed of the potential benefits/risks

NOTE: No participant should discontinue an approved IPF therapy for the purpose of enrolling in this study.

During the 48-week treatment phase of the study, co-administration of an approved IPF therapy (such as, pirfenidone or nintedanib) is acceptable if clinically indicated in the Investigator's opinion, after assessment of potential risks/benefits of such combination with blinded study treatment.

Participants who complete the 48-week study will be eligible for an optional, open-label extension phase with continued access to pamrevlumab, regardless of their randomized assignment.

Arms: arm 1: Treatment phase: Pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks.

Open-label extension phase: Pamrevlumab 30 mg/kg administered by intravenous infusion, every 3 weeks for up to 48 weeks arm 2: Pamrevlumab-matching placebo administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks
Interventions: intervention 1: Pamrevlumab intervention 2: Placebo
Intervention descriptions: intervention 1: Sterile solution for injection intervention 2: Sterile solution for injection

Protocol documents:
Prot_000.pdf: 
 TITLE PAGE 
CLINICAL STUDY PROTOCOL 
STUDY TITLE: 
Zephyrus II: A Phase 3, Randomized, Double-Blind, 
Placebo-Controlled Efficacy and Safety Study of 
Pamrevlumab in Subjects with Idiopathic 
Pulmonary Fibrosis (IPF) 
PROTOCOL NUMBER: 
FGCL-3019-095 
PHASE: 
Phase 3 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
KEY SPONSOR CONTACT(S):           Name: 
  
Title: 
 
 Mobile:  
 
E-mail Address: 
Name: 
Title: 
Mobile:  
E-mail Address:
IND NUMBER: 
EudraCT NUMBER: 
011212 
2020-000697-22 
STUDY DRUG: 
Pamrevlumab (FG-3019) 
INDICATION: 
Idiopathic Pulmonary Fibrosis 
ORIGINAL PROTOCOL: 
Amendment 0.1 Germany: 
Amendment 0.1 UK: 
Amendment 0.1 Denmark: 
Amendment 0.1 Czech Republic: 
Amendment 0.1 France: 
Amendment 1.0: 
Amendment 1.2: UK 
Amendment 2.0 
11 February 2020 
07 July 2020 
07 August 2020 
16 September 2020 
12 October 2020 
12 October 2020 
03 March 2021 
25 August 2021 
09 January 2023 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and proprietary to FibroGen, Inc. No part of 
this document or any of the information contained herein may be transmitted, disclosed, shared, 
reproduced, published or utilized by any persons without prior written authorization by FibroGen, Inc.
NCT #: NCT04419558


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INVESTIGATOR SIGNATURE PAGE 
STUDY ACKNOWLEDGEMENT 
Zephyrus II: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety 
Study of Pamrevlumab in Subjects with Idiopathic Pulmonary Fibrosis (IPF) 
 
FGCL-3019-095 
Original: 11 February 2020 
Amendment 0.1 Germany: 07 July 2020 
Amendment 0.1 UK: 07 August 2020 
Amendment 0.1 Denmark: 16 September 2020 
Amendment 0.1 Czech Republic: 12 October 2020 
Amendment 0.1 France: 12 October 2020 
Amendment 1.0: 03March2021 
Amendment 1.2 UK: 25August 2021 
Amendment 2.0: 09 January 2023 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and the current Investigator’s Brochure (IB), 
and I agree that it contains all necessary details for me and my staff to conduct this study as 
described. I will conduct this study as outlined herein and will make a reasonable effort to 
complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by FibroGen, Inc. I will discuss this material with them to ensure that they 
are fully informed about the drugs and the study. 
I will conduct the trial in accordance with the guidelines of Good Clinical Practice (GCP) 
including the archiving of essential documents, the Declaration of Helsinki, and any applicable 
local health authority, and Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) requirements. 
 
 
 
Investigator Name (Printed) 
 
Institution 
 
 
 
Signature 
 
Date 
Please return a copy of this signature page to FibroGen (or designee). Please retain the 
original for your study files. 


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CONFIRMATION OF PROTOCOL APPROVAL 
Original Protocol Date: 11 February 2020 
Amendment 0.1 Germany: 07 July 2020 
Amendment 0.1 UK: 07 August 2020 
Amendment 0.1 Denmark: 16 September 2020 
Amendment 0.1 Czech Republic: 12 October 2020 
Amendment 0.1 France: 12 October 2020 
Amendment 1.0: 03March2021 
Amendment 1.2 UK: 25 August 2021 
Amendment 2.0: 09 January 2023 
This protocol is approved by FibroGen. 
 
 
 
 
 
 
 
FibroGen, Inc. 
*See appended final page for 21 CFR 
part 11 compliant approval  
 
Date 
 
 
 
 


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AMENDMENT 2.0: KEY CHANGES 
The protocol has been edited for clarity, consistency, and quality of content (typos, grammatical 
errors, flow, etc.). A redline version documenting all changes from the previous version of this 
document is available upon request 
Description of Key Change 
Rationale for Change 
Section(s) Affected 
Primary efficacy endpoint updated from 
time to disease progression to Change 
in FVC.  Sample size calculations and 
related analysis language were adjusted 
to reflect this change 
To align the primary efficacy 
endpoint with that of the 
Zephyrus I trial   
Synopsis,  
Section 3.2.1,  
Section 8.1  
Secondary endpoints updated to reflect 
shift in primary endpoint and also to 
move several secondary endpoints to 
exploratory endpoints.  Additionally, a 
composite efficacy endpoint was added.  
Related analysis language was adjusted 
to reflect this change 
Updated and ordered for 
clinical relevance 
Synopsis,  
Section 3.2.2 
Section 8.3.4.2 
Exploratory endpoints were updated to 
include several of the previous 
secondary endpoints.  Related analysis 
language was added to reflect these 
changes. 
Updated for clinical relevance 
Synopsis  
Section 3.2.3 
Section 8.3.4.3 
Removed outdated IB language 
To remove outdated IB language.  Section 2.5,  
Section 2.6.3  
Clarified required procedures/assessments 
at early termination visits 
To further clarify the required 
procedures/assessments for early 
termination visits 
Section 4.4,  
Appendix 1,  
Appendix 4 
Added language describing infusion 
duration and post-infusion observation 
periods in the Open-label Extension.  
To further clarify the infusion 
and post-infusion observation 
periods for Open-label Extension 
visits.  
Table 1,  
Appendix 6 
Clarified requirement for medications 
and supplies for Home Health Care.  
To further clarify the 
requirement for medication and 
supplies for suspected 
hypersensitivity/analytical 
events for Home Health Care  
Section 5.1.7,  
Appendix 6 
Added preliminary non-clinical study 
results  
Preliminary results of rabbit 
embryo-fetal development 
study available to inform 
contraception 
recommendations.  
Section 5.2.3  
Added language regarding pregnancy 
testing  
To align with the CTFG v1.1. 
embryo-fetal risk contraception 
recommendations  
Section 5.2.3,  
Appendix 1,  
Appendix 2, 
Appendix 6 


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Added PK, HAHA and, HAHA-NA, 
CTGF and tryptase scheduled blood 
draws at the time of any suspected 
hypersensitivity/anaphylactic reactions  
 
To meet Regulatory 
recommendations for 
immunogenicity testing  
Synopsis,  
Section 6.2.4.2,  
Appendix 2,  
Appendix 6 
Added additional timepoints as follows 
in the main phase of the study: 
- 
CTGF: Week 24, Week 36 
- 
HAHA & HAHA-NA: Week 36, 
Week 48/Last dose/ET 
To meet Regulatory 
recommendations for 
immunogenicity testing 
Synopsis,  
Section 6.2.4.2,  
Appendix 2 
Clarified the order of Patient Reported 
Outcome questionnaire administration.  
To further clarify the order in 
which Patient Report Outcome 
questionnaires should be 
administered.  
Section 6.2.6  
OLE objective added 
Long-term safety of 
pamrevlumab added as the 
objective for the open label 
extension (OLE) phase  
Appendix 6 
Additional safety assessments – vitals 
and immunogenicity 
Clarified that pre- and post-
infusion vitals and 
immunogenicity are part of 
safety assessment in the OLE 
phase  
Appendix 6 
Clarified main study procedures and 
AEs  
To clarify main study 
procedures and AEs versus 
OLE.  
Appendix 6  
OLE Home Health care requirements 
added 
Added clarification that any 
home infusions via home health 
care are not permitted until at 
least 3 infusions in the OLE 
phase have been administered 
without safety concerns  
Appendix 6 
In addition to the changes listed above, 
minor editorial changes were made 
throughout the document to improve 
consistency and clarity  
To correct typographical errors, 
and to improve consistency and 
clarity  
 
Throughout the 
document  
 
 
 
 


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1. 
PROTOCOL SYNOPSIS 
 
 
PROTOCOL SYNOPSIS 
Study Title: 
Zephyrus II: A Phase 3, Randomized, Double-Blind, Placebo-
Controlled Efficacy and Safety Study of Pamrevlumab in Subjects 
with Idiopathic Pulmonary Fibrosis (IPF) 
Protocol Number: 
FGCL-3019-095 
Investigational Product: 
Pamrevlumab (FG-3019) 
Study Phase: 
Phase 3 
Indication: 
Idiopathic Pulmonary Fibrosis 
Number of 
Subjects Planned: 
Approximately 340 
Number of Sites Planned: 
Approximately 170  
OBJECTIVES 
The overall objective of this trial is to evaluate the efficacy and safety of pamrevlumab as 
compared to placebo in subjects with Idiopathic Pulmonary Fibrosis.   


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ENDPOINTS 
Primary Endpoint: 
•  Change in FVC (L) from baseline at Week 48 
Secondary Endpoints: 
• Time to disease progression, defined as absolute FVC percent predicted (FVCpp) 
decline of ≥10% or death, whichever occurs first 
• Change in Quantitative Lung Fibrosis (QLF) volume from baseline at Week 48 
• Time to any component of the clinical composite endpoint, whichever occurs first: 
acute IPF exacerbation, respiratory hospitalization, or death  
• Time to first acute IPF exacerbation during study    
• Time to all-cause mortality during study 
• Time to first respiratory hospitalization during study 
Exploratory endpoints: 
• 
Time to composite of: respiratory hospitalization, absolute FVCpp decline ≥10%, or 
death, whichever occurs first  
• 
Change in absolute FVCpp from baseline at Week 48  
• 
Change in relative FVCpp from baseline at Week 48  
• 
Change in St. George’s Respiratory Questionnaire (SGRQ) score from baseline at Week 
48 
• 
Change in University of California San Diego – Shortness of Breath Questionnaire 
(UCSD-SOBQ) score from baseline at Week 48  
• 
Change in Leicester Cough Questionnaire (LCQ) from baseline at Week 48 
• 
Exploratory biomarkers 
 Safety Assessments: 
Adverse events (including serious adverse events), clinical laboratory parameters, vital signs, 
immunogenicity (Human Anti-Human Antibody [HAHA] formation), and 
hypersensitivity/anaphylactic reactions. 
STUDY DESIGN 
This is a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate 
the efficacy and safety of pamrevlumab in subjects with idiopathic pulmonary fibrosis (IPF).  
Subjects who were previously treated with approved IPF therapies (i.e., nintedanib or 
pirfenidone; unless neither treatment is available in the host country) may be eligible for 
screening, provided that the subject is not currently receiving treatment with an approved IPF 
therapy.   


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NOTE: No subject should discontinue an approved IPF therapy for the purpose of enrolling in 
this study. 
Approximately 340 eligible subjects will be randomized at a 1:1 ratio to Arm A or Arm B, 
respectively:   
Arm A: pamrevlumab, 30 mg/kg IV, Day 1 and every 3 weeks thereafter  
Arm B: Matching placebo IV, Day 1 and every 3 weeks thereafter  
Randomization will be stratified by GAP stage (I, II, III) derived from the GAP score obtained 
during screening (See Appendix 5). NOTE:  For calculation of the GAP score: Use the Best-
Test Review (BTR) assessment provided by the spirometry vendor over-reader of the screening 
value (see Section 6.2.5 and Appendix 5). 
The intent of this study is to evaluate the efficacy and safety profile of pamrevlumab as 
monotherapy in subjects with IPF who were previously treated with an approved therapy but 
who discontinued that therapy (possible reasons for discontinuation of approved therapy could 
include, but are not limited to, intolerance or disease progression), unless neither treatment is 
available in the host country.  
During the treatment period, co-administration of an approved IPF therapy (i.e., pirfenidone or 
nintedanib) is acceptable if clinically indicated in the Investigator’s opinion, after assessment of 
potential risks/benefits of such combination with blinded study treatment. However, since 
subjects either tried and stopped treatment with an approved IPF therapy, or have no such 
treatment available, it is not expected that many subjects will resume treatment with an 
approved IPF therapy during this study. 
Subjects who complete the Week 48 visit of the main study (regardless of the number of study 
drug infusions received) will be eligible to participate in the optional open-label extension 
(OLE) phase of the study that offers continuing access to pamrevlumab regardless of 
randomization assignment in the main study. Details of this OLE phase are outlined in 
Appendix 6. 
Subjects who discontinue study treatment for any reason should be encouraged to remain in the 
study and be followed for all study visits and assessments.  
The following assessments will be assessed centrally:  
• Pulmonary function tests (PFTs)  
• High-resolution computed tomography (HRCT)  
• Acute IPF exacerbations and respiratory hospitalizations    
STUDY PERIODS 
The study consists of the following study phases: 
• Main (double blind, placebo-controlled) phase:  
o Screening period: Up to 6 weeks 
o Treatment period: 48 weeks  


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• Optional, open label extension (OLE) phase of pamrevlumab:  
o Access to pamrevlumab will be available until the last subject completes 48 
weeks of treatment in the OLE phase, or pamrevlumab is commercially available 
for the indication of IPF, or the Sponsor decides to end the OLE phase, 
whichever occurs first.  
• Follow-up period/final safety assessments:   
o 28 days after last dose 
o 60 days after last dose: follow-up phone call, for a final safety assessment   
Note: These two final safety assessments are to be scheduled after the last, final 
dose of study drug (e.g.: for subjects not progressing to the optional, OLE phase, the 
last dose is the one received during double blind phase; for subjects continuing in 
the OLE, it is the last pamrevlumab dose in the OLE phase).  
SUBJECT ELIGIBILITY CRITERIA 
Inclusion Criteria: 
1. Age 40 to 85 years, inclusive, at screening initiation. 
2. Diagnosis of IPF as defined by ATS/ERS/JRS/ALAT guidelines (Raghu 2018).  
3. IPF diagnosis within the past 7 years, with onset defined as the date of the first recorded 
diagnosis of IPF by HRCT and/or surgical biopsy (SLB) or other appropriate tissue 
sample (e.g., cryobiopsy) in the medical history. 
4. Interstitial pulmonary fibrosis defined by HRCT scan at screening, with evidence of 
≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing, within the 
whole lung. NOTE: this requires confirmation by an Independent Radiology Imaging 
Review Group, prior to randomization. If a recent HRCT scan (within 3 months prior to 
screening) is available, it can be utilized for screening purposes, provided it is submitted 
and evaluated by the Independent Radiology Imaging Review Group, is adhering to the 
same imaging acquisition parameters detailed in the Imaging Core Manual (ICM), and 
is either using the same accredited scanner, or is performed using the same modality, as 
the on-study HRCT scans. 
5. FVCpp value >45% and <95% at screening and Day 1(prior to randomization).  
6. Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted and 
corrected by Hb value ≥25% and ≤90% at screening (determined locally). If a DLCO is 
available within 3 months prior to screening, it can be utilized for screening purposes. 
7. Both FVC and DLCO testing must be representative of the IPF underlying disease (i.e. 
have been obtained in absence of an acute respiratory event [e.g. lung infection, cold] or 
other events that are known to affect PFT testing results [e.g., broken rib, chest pain, 
other]). 


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8. Previously treated with an approved IPF therapy (i.e., pirfenidone or nintedanib) but 
discontinued at least 1 week prior to screening, unless neither treatment is available in 
the host country. NOTE: no subject should discontinue approved therapy for the 
purpose of enrolling in this study. 
9. Male subjects with partners of childbearing potential and female subjects of 
childbearing potential (including those <1 year postmenopausal) must use a highly 
effective method of contraception per Clinical Trial Facilitation Group (CTFG) 
recommendation (see protocol section 5.2.3 for details) during the conduct of the study, 
and for 3 months after the last dose of study drug.  Women not of childbearing potential 
are defined as: 
a. Post-menopausal women (defined as at least 12 months with no menses without an 
alternative medical cause); in women < 45 years of age, a high follicle stimulating 
hormone (FSH) level in the post-menopausal range may be used to confirm a post-
menopausal state in women not using hormonal contraception or hormonal 
replacement therapy; OR 
b. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or 
bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR 
c. Have a congenital or acquired condition that prevents childbearing. 
10. Able to understand and sign a written informed consent form. 
Exclusion Criteria: 
1. Previous exposure to pamrevlumab. 
2. Evidence of significant obstructive lung disease by any of the following criteria: (1) 
forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio <0.70, or 
(2) extent of emphysema greater than the extent of fibrosis on HRCT. NOTE: this 
requires confirmation by an Independent Radiology Imaging Review Group, prior to 
randomization. 
3. Female subjects who are pregnant or nursing. 
4. Smoking within 3 months of screening and/or unwilling to avoid smoking throughout 
the study. 
5. Interstitial lung disease (ILD) other than IPF, including but not limited to any of the 
other types of idiopathic interstitial pneumonias; lung diseases related to exposure to 
fibrogenic agents or other environmental toxins or drugs; other types of occupational 
lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic 
diseases, including vasculitis, infectious diseases and connective tissue diseases. In 
cases of uncertain diagnosis, serological testing and/or review by multi-disciplinary 
team should be performed to confirm diagnosis of IPF vs. other types of ILD. 
6. Sustained improvement in the severity of IPF during the 12 months prior to screening, 
based on changes in FVC, DLCO, and/or HRCT scans of the chest. 


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7. History of other types of respiratory diseases, including diseases or disorders of the 
airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall that, in 
the opinion of the Investigator, would impact the primary protocol endpoint or 
otherwise preclude the subject’s participation in the study. 
8. Medical conditions (e.g. MI/stroke within the past 6 months), or logistical challenges 
that in the opinion of the Investigator preclude the subject’s adequate participation in the 
study. 
9. Poorly controlled chronic heart failure (NYHA Class 3 or above); clinical diagnosis of 
cor pulmonale requiring specific treatment; or severe pulmonary arterial hypertension 
requiring specific treatment that, in the opinion of the Investigator, would preclude the 
subject’s participation in the study.  
10. Clinically important abnormal laboratory tests (including serum creatinine ≥1.5 x upper 
limit of normal [ULN], hemoglobin (Hb) <10 g/dL, white blood cells <3,000/mm3, 
platelets less than 100,000/mm3, serum total bilirubin >1.5 x ULN, serum alanine 
aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 x ULN, or serum 
alkaline phosphatase ≥2 x ULN. 
11. Ongoing acute IPF exacerbation, or suspicion of such process during screening or 
randomization, including hospitalization due to acute IPF exacerbation within 4 weeks 
prior to or during screening. 
12. High likelihood of lung transplantation (in the opinion of the Investigator) within 6 
months after Day 1. 
13. Use of any investigational drugs or unapproved therapies, or participation in any clinical 
trial with an investigational new drug within 30 days prior to screening. 
14. Daily use of PDE-5 inhibitor drugs (e.g. sildenafil, tadalafil) except for treatment of 
severe pulmonary artery hypertension. 
15. Any current malignancy (this does not include localized cancer such as basal or 
squamous cell carcinoma of skin). Any history of malignancy likely to result in 
mortality, or requiring significant medical or surgical intervention within the next year. 
16. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies, or to any component of the excipient. 
17. Any condition (other than IPF) that is likely to result in the death of the patient within 
the next year. 
18.  Acute infection requiring any of the following: 
a. Hospital admission for ≥24 hours within four weeks prior to screening, or during 
screening 
b. Treatment with antibiotics (IV, IM, oral, or inhaled) within four weeks prior to 
screening, or during screening 
c. Active or recent (≤4 weeks prior to randomization) upper or lower respiratory 
tract infection 
d. Active tuberculosis requiring treatment within 12 months prior to screening 


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19. Known history of immunodeficiency, including but not limited to HIV infection. 
20. Receipt of a live/attenuated vaccine within the four weeks prior to randomization.  
21. Chronic treatment with any of the following within four weeks or five half-lives 
(whichever is longer) prior to randomization, if used to treat IPF: 
a. Immunosuppressive or immunomodulatory therapies (e.g., azathioprine, 
cyclosporine A, cyclophosphamide, D-penicillamine, interferon-gamma, tumor 
necrosis factor- α antagonists) 
b. Cytotoxic drugs (e.g., colchicine) 
22. The Investigator judges that the subject will be unable to fully participate in the study 
and complete it for any reason, including inability to comply with study procedures and 
treatment, addiction, or any other relevant medical or psychiatric conditions. 
23. Country Specific Criteria (Czech Republic Only): Positive result from a Tuberculosis 
(TB) screening test performed within 6 months prior to screening for the study. TB 
testing may be done locally. 
STUDY TREATMENT 
Dose and Mode of Administration: 
Main Phase (Double-Blind, Placebo-Controlled):  
Pamrevlumab or placebo, 30 mg/kg, IV, Day 1 and every 3 weeks thereafter, up to Week 48, 
for a total of  up to 17 infusions. 
Optional, Open Label Extension (OLE) Phase of Pamrevlumab: 
Pamrevlumab (30 mg/kg) every 3 weeks  
Other Important Information: 
Other medications and therapies intended to treat IPF, other than approved IPF therapies 
(pirfenidone or nintedanib), will not be allowed during the study except for some protocol-
specified exceptions. 
Study drug should not be administered to subjects with a history of allergic or anaphylactic 
reaction to human, humanized, or chimeric monoclonal antibodies, or to any of the components 
of the excipient. 
 


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STATISTICAL METHODS 
Sample Size Calculations: 
This study will enroll approximately 340 subjects with a 1:1 randomization ratio to either 
pamrevlumab or placebo.  
A sample size of 340 subjects will have at least 90% power, based on a two-sided alpha level of 
0.05 for a two-sample t-test, to detect a treatment difference of 120 mL in the primary efficacy 
endpoint, change from baseline in FVC (L), assuming a standard deviation of 300 mL. This 
sample size allows for a dropout rate of approximately 20%. 
 
Statistical Analysis Methods: 
The primary efficacy endpoint, change from baseline to Week 48 in FVC (L), will be analyzed 
using a random coefficient model (RCM) with treatment, visit, visit-by-treatment interaction, 
randomization stratification factor, baseline FVC volume, age, sex, height as fixed effects; the 
intercept and linear slope of visit are random effects.  
For the other efficacy endpoints, unless stated otherwise, the RCM model will be used for 
pulmonary function test variables; the Mixed Model for Repeated Measure (MMRM) model 
will be used for patient reported outcome questionnaires and other continuous variables; and the 
Cox regression model will be used in time-to-event variables. The analysis models will include 
the stratification factor and appropriate baseline factors.   
Safety Analyses:  
All subjects who received any dose of study treatment will be included in the safety analyses. 
Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events 
(TESAEs) will be summarized by treatment arm.  
Clinically significant changes from baseline in vital signs and laboratory tests will be identified 
and summarized by treatment arm. Additionally, hypersensitivity/anaphylactic and 
immunogenicity reactions will be monitored and assessed. 
Safety data collected during the OLE phase will be summarized descriptively. 
OPTIONAL BLOOD DRAWS 
Optional Pharmacokinetics (PK) and Genomic Analyses:  
Two optional sub-studies, one for PK assessment, and one for genomic analyses, will be 
performed in a subset of subjects at select sites. Such subjects will provide their consent to 
these optional sub-studies prior to their participation in these sub-studies. PK assessments will 
continue to be optional except in the case of suspected hypersensitivity/anaphylactic reactions (see 
Section 6.2.4.2.3 for more detail).  
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
and the applicable regulatory requirement(s), including the archiving of essential documents. 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
AMENDMENT 2.0: KEY CHANGES ...........................................................................................4 
1. 
PROTOCOL SYNOPSIS .............................................................................................6 
2. 
INTRODUCTION ......................................................................................................19 
2.1. 
Description of Pamrevlumab ......................................................................................19 
2.2. 
Idiopathic Pulmonary Fibrosis ....................................................................................19 
2.3. 
Connective Tissue Growth Factor ..............................................................................22 
2.4. 
Connective Tissue Growth Factor in Idiopathic Pulmonary Fibrosis ........................23 
2.5. 
Clinical Trial Experience with Pamrevlumab .............................................................23 
2.6. 
Rationale for Pamrevlumab in Idiopathic Pulmonary Fibrosis ..................................24 
2.6.1. 
Clinical Studies in IPF ................................................................................................24 
2.6.2. 
Dose Rationale ............................................................................................................25 
2.6.3. 
Safety Summary, and Benefit – Risk Assessment ......................................................26 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................28 
3.1. 
Objective .....................................................................................................................28 
3.2. 
Endpoints ....................................................................................................................28 
3.2.1. 
Primary Endpoint: .......................................................................................................28 
3.2.2. 
Secondary Endpoints ..................................................................................................28 
3.2.3. 
Exploratory Endpoints ................................................................................................28 
3.2.4. 
Safety Assessment ......................................................................................................28 
3.3. 
Overall Study Design ..................................................................................................29 
3.3.1. 
Study Duration ............................................................................................................30 
3.3.2. 
Placebo Control Group ...............................................................................................31 
3.4. 
Randomization and Treatment Assignment ................................................................31 
3.4.1. 
Randomization ............................................................................................................31 
3.4.2. 
Treatment Assignment ................................................................................................31 
3.5. 
Blinding ......................................................................................................................32 
3.5.1. 
Maintenance of Blinding ............................................................................................32 
3.5.2. 
Request for Unblinding of Treatment Assignment .....................................................32 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................33 
4.1. 
Subject Inclusion Criteria ...........................................................................................33 


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4.2. 
Subject Exclusion Criteria ..........................................................................................34 
4.3. 
Subject Study Withdrawal Criteria .............................................................................36 
4.4. 
Subject Study Withdrawal Procedures/Assessments ..................................................36 
4.5. 
Replacement of Study Subjects ..................................................................................37 
4.6. 
Study Closure ..............................................................................................................37 
5. 
TREATMENT OF SUBJECTS ..................................................................................38 
5.1. 
Study Treatment ..........................................................................................................38 
5.1.1. 
Pamrevlumab or Placebo ............................................................................................38 
5.1.2. 
Formulation .................................................................................................................38 
5.1.3. 
Study Drug Packaging and Labeling ..........................................................................38 
5.1.4. 
Study Drug Storage .....................................................................................................38 
5.1.5. 
Study Drug Preparation ..............................................................................................38 
5.1.6. 
Study Drug Administration .........................................................................................38 
5.1.7. 
Home Health Care ......................................................................................................40 
5.1.8. 
Missed Dose ................................................................................................................41 
5.1.9. 
Study Drug Handling and Disposal ............................................................................41 
5.1.10. 
Co-Administration of an Approved IPF Therapy .......................................................41 
5.1.11. 
Treatment Compliance ................................................................................................41 
5.2. 
Concomitant Medications ...........................................................................................42 
5.2.1. 
Permitted Concomitant Medications ..........................................................................42 
5.2.2. 
Prohibited Concomitant Medications .........................................................................42 
5.2.3. 
Contraception Requirements ......................................................................................43 
6. 
ASSESSMENTS OF EFFICACY ..............................................................................45 
6.1. 
Study Assessments ......................................................................................................45 
6.1.1. 
Screening Period .........................................................................................................45 
6.1.2. 
Treatment Period ........................................................................................................45 
6.1.3. 
Safety Follow-Up ........................................................................................................45 
6.1.4. 
Early Study Termination Visit ....................................................................................46 
6.1.5. 
Missed Visits ..............................................................................................................46 
6.1.6. 
Unscheduled Visits .....................................................................................................46 
6.2. 
Assessments ................................................................................................................47 
6.2.1. 
Vital Signs (including Weight and Height) ................................................................47 
6.2.2. 
Physical Exam ............................................................................................................47 


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6.2.3. 
Electrocardiogram (ECG or EKG) .............................................................................47 
6.2.4. 
Laboratory Evaluations ...............................................................................................47 
6.2.4.1. 
Central Laboratory Evaluations ..................................................................................47 
6.2.4.2. 
Pharmacokinetics (PK) and Pharmacodynamics ........................................................49 
6.2.5. 
High Resolution Computerized Tomography (HRCT) Scans and Spirometry ..........51 
6.2.6. 
Patient Reported Outcomes (PROs) ...........................................................................51 
6.2.6.1. 
St. Georges Respiratory Questionnaire (SGRQ) ........................................................52 
6.2.6.2. 
University of California, San Diego – Shortness of Breath Questionnaire 
(UCSD-SOBQ) ...........................................................................................................52 
6.2.6.3. 
Leicester Cough Questionnaire (LCQ) .......................................................................52 
7. 
ASSESSMENTS OF SAFETY ..................................................................................53 
7.1. 
Background .................................................................................................................53 
7.2. 
Definitions ..................................................................................................................53 
7.2.1. 
Definition of an Adverse Event (AE) .........................................................................53 
7.2.2. 
Definition of a Serious Adverse Event (SAE) ............................................................53 
7.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events ........................54 
7.3.1. 
Adverse Event Reporting Period ................................................................................54 
7.3.2. 
Adverse Event Eliciting/Reporting .............................................................................54 
7.3.3. 
Assessing Adverse Event Severity .............................................................................55 
7.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug ......................................55 
7.3.5. 
Reporting Serious Adverse Events (SAEs) ................................................................56 
7.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review Board / 
Independent Ethics Committee ...................................................................................57 
7.3.5.2. 
Deaths .........................................................................................................................57 
7.3.6. 
Pregnancies: Reporting and Follow-up of Subjects and Female Partners of 
Subjects .......................................................................................................................57 
7.3.7. 
Laboratory or other Test Abnormalities/ Findings .....................................................58 
7.3.8. 
Hypersensitivity/Anaphylactic Reactions: ..................................................................58 
7.3.9. 
Safety Monitoring .......................................................................................................59 
7.3.9.1. 
Special Reporting Situations .......................................................................................59 
7.3.9.2. 
Data Monitoring Committee (DMC) ..........................................................................59 
8. 
STATISTICS ..............................................................................................................60 
8.1. 
Sample Size Determination ........................................................................................60 


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8.2. 
Analysis Populations ..................................................................................................60 
8.2.1. 
Intent to Treat (ITT) Population .................................................................................60 
8.2.2. 
Safety Population ........................................................................................................60 
8.3. 
Statistical Analysis ......................................................................................................60 
8.3.1. 
General Considerations ...............................................................................................60 
8.3.2. 
Subject Enrollment and Disposition ...........................................................................61 
8.3.3. 
Demographics and Baseline Characteristics ...............................................................61 
8.3.4. 
Efficacy Analyses .......................................................................................................61 
8.3.4.1. 
Primary Endpoint Analysis .........................................................................................61 
8.3.4.2. 
Secondary Endpoint Analyses ....................................................................................62 
8.3.4.3. 
Exploratory Analyses ..................................................................................................62 
8.3.5. 
Pharmacokinetic Analyses ..........................................................................................63 
8.3.6. 
Safety Analyses ..........................................................................................................63 
8.4. 
Interim Analysis ..........................................................................................................63 
8.5. 
Statistical Analysis Plan .............................................................................................63 
9. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................64 
9.1. 
Data Quality Assurance ..............................................................................................64 
9.2. 
Audit and Inspection ...................................................................................................64 
10. 
ETHICS ......................................................................................................................65 
10.1. 
Ethical Considerations ................................................................................................65 
10.2. 
Communication with the Institutional Review Board or Independent Ethics 
Committee ...................................................................................................................65 
10.3. 
Subject Information and Consent ...............................................................................65 
10.4. 
Subject Confidentiality ...............................................................................................66 
11. 
DATA HANDLING AND RECORD KEEPING ......................................................67 
11.1. 
Source Documents ......................................................................................................67 
11.2. 
Direct Access to Source Documents ...........................................................................67 
11.3. 
Data Collection, Handling, and Verification ..............................................................67 
11.4. 
Protocol Deviations ....................................................................................................67 
11.5. 
Retention of Data ........................................................................................................68 
11.6. 
Financial Disclosure ...................................................................................................68 
12. 
PUBLICATION POLICY ..........................................................................................69 
13. 
REFERENCES ...........................................................................................................70 


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14. 
APPENDICES ............................................................................................................77 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................78 
APPENDIX 2. PHARMACOKINETIC, BIOMARKER, IMMUNOGENICITY AND   
GENOMICS SAMPLING ..................................................................................81 
APPENDIX 3. HRCT CRITERIA AND HISTOPATHOLOGICAL CRITERIA FOR 
UIP PATTERN ...................................................................................................82 
APPENDIX 4. RADIATION RISK ASSESSMENT .................................................................84 
APPENDIX 5. GAP SCORE CALCULATION .........................................................................86 
APPENDIX 6. OPTIONAL, OPEN LABEL EXTENSION (OLE) PHASE OF 
PAMREVLUMAB .............................................................................................87 
 
LIST OF TABLES 
Table 1 
Pamrevlumab (or placebo): Dose, Route, and Administration ...................................39 
Table 2: 
Laboratory Tests .........................................................................................................48 
 
LIST OF FIGURES 
Figure 1: 
FGCL-3019-095 Study Schema .................................................................................31 
 
 


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2. 
INTRODUCTION 
2.1. 
Description of Pamrevlumab 
Pamrevlumab is a recombinant fully human immunoglobulin G1 (IgG) kappa monoclonal 
antibody that binds to connective tissue growth factor (CTGF) and is being developed for 
treatment of diseases in which tissue fibrosis has a major pathogenic role, as  hepatitis induced 
liver fibrosis, idiopathic pulmonary fibrosis, certain fibrotic cancers and Duchenne muscular 
dystrophy (DMD). Pamrevlumab (MW ~150 kDa) is produced by mammalian Chinese hamster 
ovary (CHO) fed-batch cell culture system. Pamrevlumab contains 1,326 amino acids and binds 
with high affinity to domain 2 of CTGF (dissociation constant: Kd=0.1–0.2 nM). 
2.2. 
Idiopathic Pulmonary Fibrosis 
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fatal lung disease of unknown 
etiology characterized by fibrotic interstitial infiltrates that are consistent with the 
histopathologic pattern of usual interstitial pneumonia (Gross, 2001, Raghu, 2018). IPF is the 
most common of seven recognized types of idiopathic interstitial pneumonia (Kim, 2006,  
Travis, 2013). 
The pathogenesis of IPF has not been clearly defined. The long-held view that fibrosis in IPF is 
triggered by chronic inflammation (alveolitis) has given way to the current belief that IPF is a 
disorder caused by repetitive epithelial injury (Selman, 2001, Selman, 2006, Wilson, 2009). The 
recurrent, subclinical epithelial injury superimposed on accelerated epithelial aging leads to 
aberrant repair of the injured alveolus and deposition of interstitial fibrosis by myofibroblasts 
(Lederer 2018).  According to this hypothesis, alveolar cell injury and activation initiate a 
dysregulated, exaggerated fibrotic healing process characterized by myofibroblast proliferation 
and progressive deposition of extracellular matrix (ECM) in genetically susceptible individuals 
(Agostini, 2006, Gross, 2001, Selman, 2004, Selman, 2006, Willis, 2006). ECM deposition and 
other pathologic processes in IPF, including epithelial basement membrane disruption, 
angiogenesis, smooth muscle cell proliferation, infiltration of mononuclear cells, accumulation 
of loose connective tissue, and cyst formation, eventually remodel the normal lung architecture 
and impair the lung’s ability to perform gas exchange. 
Exogenous and endogenous insults to the alveolar epithelium have been proposed as possible 
stimuli of the fibrotic process in IPF, but conclusive associations have not been established. The 
most commonly cited exogenous triggers of alveolar injury are exposure to cigarette smoke 
(Baumgartner, 1997, Flaherty, 2004) and environmental and occupational dusts (Hubbard, 2001, 
Taskar, 2006), viral infection (Kelly, 2002, Tang, 2003), and gastroesophageal reflux (Raghu, 
2006). Alveolar epithelial cell apoptosis and failure of alveolar re-epithelialization (Barbas-Filho, 
2001, Li, 2004, Selman, 2001, Selman, 2006), resistance of myofibroblasts to apoptosis 
(Thannickal, 2006), shortened telomeres, oxidative injury, proteostatic dysregulation and 
endoplasmic reticulum stress, and mitochondrial dysfunction lead to decreased alveolar 
epithelial-cell proliferation and secretion of profibrotic mediators (Beeh, 2002, Cantin, 1987, 
Daniil, 2008, Hunninghake, 2005, Waghray, 2005, Alder 2008, Selman 2014). Additionally, 
activation of the coagulation cascade (Chambers, 2008, Selman, 2001), and circulating bone 
marrow-derived fibroblast precursors (fibrocytes) (Andersson-Sjoland, 2008, Hashimoto, 2004) 
have also been implicated in the pathogenesis of IPF. Genetic factors may play a role, as gene 


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mutations account for some cases of familial IPF (Lawson, 2006), including mutations in the 
gene encoding surfactant protein C and telomerase genes that are responsible for telomere length 
shortening (Armanios, 2007, Loyd, 2008, Tsakiri, 2007). 
Transforming growth factor-beta (TGF-β) is considered a key cytokine that is thought to drive 
the fibrotic process in IPF (Agostini, 2006, Bergeron, 2003). However, many other proteins have 
been implicated in regulation of the complex process of cellular interactions among activated 
epithelial cells, myofibroblasts, fibroblasts, macrophages, endothelial cells, and lymphocytes, 
including connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), tumor 
necrosis factor-alpha (TNF-α), endothelin-1, interleukin (IL)-1β, IL-4, IL-10, IL-13, IL-17, 
osteopontin, matrix metalloproteases, and multiple chemokines (Agostini, 2006, Ask, 2006, 
Pardo, 2006, Selman, 2004, Selman, 2006, Strieter, 2007, Wilson, 2009). The roles of epithelial-
mesenchymal transition (EMT) and circulating fibrocytes and other extrapulmonary fibroblast 
progenitor cells in expanding the myofibroblast population within the lung have been the subject 
of active debate (Lama, 2006, Strieter, 2009, Willis, 2006, Kage 2012). Connective tissue growth 
factor is a central mediator of tissue remodeling and fibrosis and has been reported to be essential 
for the fibrotic activity of TGF- β (Blom, 2002, Grotendorst, 1997, Wang 2011, Lipson, 2012). 
The epidemiology of IPF is not clearly defined. A report of a population-based study of adults 
with IPF in Olmstead County, Minnesota, from 1997 to 2005, revealed a prevalence of IPF of 
27.9 to 63 cases per 100,000, and an incidence of 8.8 to 17.4 cases per 100,000, again depending 
on the diagnostic criteria (Fernandez Perez, 2010). In the United States, the prevalence of IPF 
has been reported to range from 10 to 60 cases per 100,000, although in one study, the 
prevalence was 494 cases per 100,000 in 2011 among adults over the age of 65 years, which was 
twice as high as the prevalence recorded 10 years earlier (Lederer, 2018). The prevalence of IPF 
increases with age, and most IPF patients are age 60 or older at the time of diagnosis, although it 
is unclear whether this reflects increased recognition or a true increase in incidence  
(Lederer, 2018) The disease is more common in men than in women (Fernandez Perez, 2010). 
Most patients are current or former smokers. A familial form of IPF may account for as many as 
20% of cases of IPF (Loyd, 2008). 
Patients with IPF suffer from progressive dyspnea and cough, and most have been symptomatic 
for several years by the time of their initial presentation. Delayed diagnosis is therefore common. 
Physical examination often reveals bibasilar inspiratory crackles, but it may be normal. Digital 
clubbing is observed in about one quarter of IPF patients (King, Jr., 2001). The chest radiograph 
reveals non-specific bilateral, reticular infiltrates in the periphery of the lower lung zones, often 
with findings suggestive of pulmonary hypertension. Pulmonary function tests demonstrate 
reduced lung volumes, proportionate reduction in the pulmonary diffusing capacity, and a normal 
to increased FEV1/FVC ratio (Martinez, 2006). Arterial hypoxemia, oxyhemoglobin 
desaturation, and an increased alveolar-arterial oxygen gradient that worsens with exercise are 
typically observed in patients with IPF (Idiopathic pulmonary fibrosis: diagnosis and treatment. 
International consensus statement. American Thoracic Society (ATS), and the European 
Respiratory Society (ERS), 2000, King, Jr., 2001). High resolution computed tomography 
(HRCT) scans display subpleural reticular abnormalities and honeycombing, especially in the 
lung bases (Kim, 2006). Traction bronchiectasis is a common finding. The presence of extensive 
ground glass opacities, peribronchial and perivascular predominance of infiltrates, discrete lung 
cysts, small nodules, air trapping, mosaic attenuation, and consolidation suggest alternative 


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diagnoses (Misumi, 2006). The sensitivity and specificity of HRCT for the diagnosis of IPF in 
the hands of expert radiologists approach 90% and 80%, respectively (Kim, 2006, Raghu, 1999). 
Acute exacerbations of IPF, defined as an acute, clinically significant respiratory deterioration 
(acute worsening or development of dyspnea typically <1 mo duration) characterized by 
evidence of new widespread alveolar abnormality (computed tomography with new bilateral 
ground-glass opacity and/or consolidation superimposed on a background pattern consistent with 
usual interstitial pneumonia pattern), not fully explained by cardiac failure or fluid overload 
(Collard, 2016). These exacerbations are the leading cause of hospitalization and death in 
patients with IPF (Kondoh, 2010, Daniels 2008, Kim, 2015). The etiology of acute exacerbations 
of IPF remains uncertain, and its pathobiology may be related to intrinsic biological dysfunction 
of the lung that makes individuals with IPF more susceptible to external insults than individuals 
without IPF (Collard, 2016). A meta-analysis of six clinical trials in patients with IPF revealed a 
weighted average of 4.1 acute exacerbations per 100 patient-years (Atkins, 2014).  A less 
common, rapidly progressive form of IPF, which is common in actively smoking males, has been 
described (Selman, 2007). 
The diagnosis of IPF is suspected when the clinical and radiographic features described above 
occur in a patient with no known risk factors for interstitial disease and after other types of 
idiopathic interstitial pneumonias have been excluded. Transbronchial lung biopsy and 
bronchoalveolar lavage are occasionally performed to rule other causes of lung infiltrates. The 
diagnosis of IPF is confirmed when HRCT demonstrates definite features of “usual interstitial 
pneumonia” (UIP) (Subpleural and basal predominant reticular infiltrates; distribution is often 
heterogeneous, Honeycombing with or without peripheral traction bronchiectasis or 
bronchiolectasis) in the appropriate clinical setting. For patients with newly detected Interstitial 
lung disease (ILD) of apparently unknown cause who are clinically suspected of having IPF and 
have an HRCT pattern of UIP, the current recommendation is to not perform Surgical Lung 
Biopsy (SLB) (strong recommendation). On the other hand, patients with an HRCT pattern of 
probable UIP, indeterminate, or an alternative diagnosis, SLB is recommended (conditional 
recommendation) (Raghu, 2018).  
The histopathologic pattern of UIP is a dense fibrosis with architectural distortion (i.e., 
destructive scarring and/or honeycombing), predominant subpleural and/or paraseptal 
distribution of fibrosis, patchy involvement of lung parenchyma by fibrosis, fibroblast foci, and 
the absence of features to suggest an alternate diagnosis (Raghu, 2018). These histopathologic 
features are more commonly found in subpleural regions in the lower lung zones. Interstitial 
infiltrates of lymphocytes and plasma cells are usually not prominent (Visscher, 2006).
Pirfenidone and nintedanib are approved drugs for the treatment of IPF. In addition to these 
drugs, IPF patients are usually managed with supportive measures such as symptomatic 
treatment of cough and dyspnea, supplemental oxygen for hypoxemia, smoking cessation, 
pulmonary rehabilitation, and prophylaxis and control of respiratory tract infections (Idiopathic 
pulmonary fibrosis: diagnosis and treatment. International consensus statement. American 
Thoracic Society (ATS), and the European Respiratory Society (ERS), 2000, (Collard, 2004, 
Walter, 2006, Wuyts, 2009). Corticosteroids and the immunosuppressive drugs 
cyclophosphamide and azathioprine were commonly prescribed for IPF in the past, but there is 
no evidence that these drugs improve patient outcomes or alter the natural course of the disease 
(Collard, 2004, Walter, 2006). Furthermore, IPF subjects taking a combination of prednisone, 


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azathioprine, and N-acetylcysteine (NAC) in one arm of a three-arm multicenter Phase 3 clinical 
trial experienced increased risks of hospitalization and death compared with those taking NAC 
only or placebo only (Raghu, 2012). A multicenter Phase 3 randomized trial of warfarin in 
patients with progressive IPF was stopped because of increased mortality in subjects taking 
warfarin compared with those taking placebo (Noth, 2012). Lung transplantation is the only 
treatment that improves survival (Noth, 2007, Walter, 2006, Lancaster 2019), but most IPF 
patients are not eligible for transplantation because of their age or comorbid conditions. 
In two Phase 3 clinical trials examining the safety and efficacy of pirfenidone in patients with 
IPF, the mean decline in percent predicted FVC (FVCpp) from baseline to 72 weeks was 12.4% 
in one group receiving placebo and 9.6% in the other placebo group (Karimi-Shah, B., 2010). As 
the interstitial fibrosis and architectural distortion advance in IPF, the lung becomes more 
noncompliant, and the work of breathing and dyspnea increase. Progressive pulmonary 
hypertension and cor pulmonale often characterize the late course of the disease.  
Several retrospective studies suggest that the median survival time from diagnosis is 2–3 years 
(Raghu, 2011). The 5-year survival rate of patients with IPF is approximately 20% to 40%  
(Kim, 2006), which is worse than that of all major cancers except cancer of the lung, pancreas, 
and esophagus (Siegel, 2012). Mortality from IPF was reported to have increased 28% in men 
and 41% in women between 1992 and 2003 (Olson, 2007). The majority of IPF patients die from 
complications of the disease, such as respiratory failure, pulmonary hypertension, and 
pneumonia, or from coronary artery disease (Daniels, 2008, Gross, 2001, Martinez, 2005,  
Olson, 2007).  
2.3. 
Connective Tissue Growth Factor 
Connective tissue growth factor is a 38 kDa secreted matricellular glycoprotein of the cysteine-
rich 61/CTGF/nephroblastoma overexpression (CCN) family (Perbal, 2004, Rachfal, 2005) 
which was recently renamed cellular communication network family (Perbal 2018). It is 
produced by many cells, including fibroblasts, myofibroblasts, endothelial cells, mesangial cells, 
and stellate cells. 
The name “connective tissue growth factor” implies a mechanism of action akin to that of 
classical growth factors, which signal through specific cell-surface receptors. However, 
experimental evidence does not support this concept. Instead, CTGF and the other members of 
the CCN family have activities associated with matricellular proteins that function in a more 
subtle modulatory fashion. Matricellular proteins, with prototypical representatives including 
secreted protein acidic and rich in cysteine (SPARC), osteopontin, and thrombospondins, are a 
subclass of ECM proteins that modulate cellular functions and signaling pathways through 
multiple mechanisms depending on cell type and the cellular context (Bornstein, 2002). These 
proteins are generally expressed at high levels during development and in response to injury; 
they typically bind to multiple cell-surface receptors, ECM components, growth factors, and 
cytokines. Connective tissue growth factor fits squarely within this definition (Chen, 2009). The 
cellular functions that can be modulated by CTGF include secretion and/or organization of ECM, 
cell proliferation, survival, adhesion, migration and EMT. Modulation of cellular signaling 
appears to occur through interactions of CTGF with 1) cell surface components such as integrins 
or the low density lipoprotein receptor-related protein (LRP)-1 (a multifunctional endocytic and 
signaling receptor), 2) cytokines and cytokine inhibitors, and 3) matrix components such as 


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heparin sulfate proteoglycans (HSPGs) and fibronectin. Interactions with HSPGs may displace 
other HSPG-binding proteins such as vascular endothelial growth factor (VEGF) and bone 
morphogenetic proteins (BMPs). It is believed that binding of cytokines to CTGF may either 
sequester them in an inactive conformation, or help to present cytokine binding partners to their 
receptors. 
Connective tissue growth factor is a central mediator of tissue remodeling and fibrosis  
(Lipson, 2012). Connective tissue growth factor is essential for the fibrotic activity of TGF-β 
(Mori, 1999, Wang, 2011) but it may also act independently of TGF-β. While much has been 
made of the role of TGF-β in fibrosis, studies of the role of fibronectin in pulmonary fibrosis 
showed that the activity of TGF-β is dependent on cellular fibronectin to induce myofibroblast 
differentiation and that cellular fibronectin may have a fundamental role in activation of latent 
TGF-β (Muro, 2008). Shi-wen and colleagues showed that critical activities of TGF-β in the 
fibrotic process are dependent on CTGF expression, including EMT and ECM deposition, 
supporting the idea that CTGF over-expression is critical for activities attributed to TGF-β  
(Shi-wen, 2006). 
Connective tissue growth factor has been shown to be an important mediator of pulmonary 
fibrosis in a mouse model of bleomycin-induced pulmonary fibrosis (Bonniaud, 2004). Lasky 
and coworkers observed upregulation of CTGF messenger ribonucleic acid (mRNA) gene 
expression in a mouse model of bleomycin-induced pulmonary fibrosis, suggesting a possible 
role of CTGF in the pathogenesis of lung fibrosis (Lasky, 1998). 
2.4. 
Connective Tissue Growth Factor in Idiopathic Pulmonary Fibrosis 
Transcripts of genes for TGF-β1 and CTGF were reported to be approximately 7-fold and 4-fold 
higher, respectively, in transbronchial lung biopsy specimens of patients with IPF compared with 
normal (Ziesche, 1999). TGF-β is expressed at fibrogenic foci in IPF (Broekelmann, 1991). 
Increased CTGF gene expression has been described in transbronchial biopsy specimens and in 
bronchoalveolar lavage fluid in patients with IPF (Allen, 1999, Pan, 2001). Allen and coworkers 
also reported that CTGF mRNA expression is increased 10-fold in bronchoalveolar lavage fluid 
in patients with IPF, compared with healthy control subjects (Allen, 1999). Connective tissue 
growth factor in plasma was reported to be elevated in IPF patients and the abundance correlated 
with change in FVC (Kono, 2011). These observations suggest that CTGF may have a role in the 
pathogenesis of IPF. 
2.5. 
Clinical Trial Experience with Pamrevlumab 
The clinical trial experience with pamrevlumab is presented in the current Investigator’s 
Brochure (IB). Overall, pamrevlumab has been well tolerated.  
Adverse events (AEs) have been generally mild or moderate in severity and transient in duration. 
The AEs have been typical of the subjects’ underlying medical condition(s) and, in placebo-
controlled studies, were equally distributed between the placebo and pamrevlumab treatment 
groups. Infusions of pamrevlumab have been well tolerated.  
Duration of exposure to pamrevlumab by indication is described in the current version of the IB. 
See the IB for additional information. 


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2.6. 
Rationale for Pamrevlumab in Idiopathic Pulmonary Fibrosis 
The observations that CTGF is a central mediator in the process of fibrosis suggest a potential 
role for pamrevlumab in interfering with the activity of CTGF and thereby preventing or 
reversing fibrotic lung damage in IPF. Connective tissue growth factor is considered a potential 
target for therapeutic intervention in pulmonary fibrosis (Antoniou, 2007, Ask, 2006,  
Blom, 2002, Bonniaud, 2004, Grotendorst, 1997). 
In a mouse model of radiation-induced pulmonary fibrosis (Bickelhaupt et al, 2017), 
pamrevlumab at 10 mg/kg or placebo was administered by IP injection 3 times a week for 8 
weeks starting before or up to 16 weeks after the irradiation. Pamrevlumab-treated mice 
demonstrated better survival compared with untreated irradiated mice. Pamrevlumab attenuated 
lung remodeling, improved pulmonary function, and improved lung density in a schedule 
dependent manner. Additional observations in gene-expression changes in the lungs also 
indicated that pamrevlumab can disrupt physiological tissue remodeling after the process has 
begun.  In particular, pamrevlumab appears to disrupt a CTGF autocrine loop in mesenchymal 
cells like myofibroblasts that reduces their recruitment of leukocytes like macrophages, mast and 
dendritic cells via chemokine secretion.  This disruption results in collapse of the cellular 
crosstalk that drives tissue remodeling (Sternlicht et al, 2018). 
In another study, administration of pamrevlumab to mice with bleomycin-induced pulmonary 
fibrosis significantly inhibited lung hydroxyproline content, a marker of lung collagen content 
(FibroGen, 2003, data on file). 
These preclinical findings are supported by preliminary efficacy data in the FGCL-3019-049 
study, which suggest that treatment of subjects with IPF with pamrevlumab 15 mg/kg and 30 
mg/kg IV every 3 weeks is associated with improvement or stability in quantified scores of 
whole lung fibrosis in approximately 45 percent of subjects at 24 weeks (Raghu, 2012). Changes 
from baseline in these scores were significantly correlated with changes in FVCpp value (Raghu, 
2012). In 2012, the Food and Drug Administration (FDA) granted Orphan Drug Designation to 
pamrevlumab for the treatment of IPF. Additionally, results from the Phase 2, randomized, 
double-blind, placebo-controlled trial of pamrevlumab in IPF (Study 067) has shown a 
statistically significant difference from placebo for the primary efficacy endpoint of FVCpp 
change from baseline to week 48 favoring pamrevlumab. Other important efficacy endpoints 
favoring pamrevlumab include: proportion of subjects with disease progression, time to disease 
progression, change from baseline in lung fibrosis (QLF, FIB) score to Week 48 measured by 
quantitative HRCT, patient-reported quality of life measurements using the SGRQ (positive 
trends) and the UCSD-SOBQ, as well as favorable trend in all-cause mortality. These results of 
an open-label Phase 2 study and a randomized placebo-controlled Phase 2 study suggest 
pamrevlumab slows the progression of IPF as measured by change in FVCpp, quantitative 
analysis of fibrosis, and time to disease progression or death. 
2.6.1. 
Clinical Studies in IPF 
FibroGen has sponsored 5 studies in idiopathic pulmonary fibrosis (IPF), three Phase 1 / 2 
studies that are completed, and two Phase 3 studies that are ongoing. 


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Study FGCL-MC3019-002, was a Phase 1 open-label, dose-escalation study to determine the 
safety, pharmacokinetics, immunogenicity, and bioactivity of escalating single doses of 
pamrevlumab in subjects with IPF; a total of 21 subjects were treated with pamrevlumab. 
Study FGCL-3019-049, was an open-label, Phase 2 study to evaluate the safety, tolerability, and 
efficacy of pamrevlumab in subjects with IPF; subjects were treated with 2 doses of 
pamrevlumab every 3 weeks: 15mg/kg and 30mg/kg. Subjects who met extension criteria 
continued to receive pamrevlumab treatment every 3 weeks until disease progression. Results of 
the 049 study were published (Raghu et al. 2016, Clukers et al. 2018). 
Study FGCL 3019-067 (PRAISE Study), was a Phase 2, randomized, double-blind, placebo-
controlled study in subjects with IPF to evaluate the safety and efficacy of pamrevlumab 
administered at 30 mg/kg by IV infusion every 3 weeks for 45 weeks for a total of 16 infusions. 
Following the double-blind randomized treatment period, qualifying subjects had the option to 
enter an open-label extended treatment period to receive pamrevlumab 30 mg/kg every 3 weeks. 
Fifty subjects were randomized to pamrevlumab and fifty-three were randomized to placebo in 
the main study. The study was amended to include an additional subset of subjects (called “sub-
study” to differentiate from the “main” study) receiving background IPF approved therapy with 
pirfenidone or with nintedanib in a stratified manner. For the sub-study, the randomized double-
blind placebo-controlled treatment period was 24 weeks with no extended treatment period. 
For details on studies 049 and 067 (main study, extended treatment period, and the sub-study) 
see Section 2.6.3 below, and the current version of the IB. Results of the PRAISE study were 
published (Richeldi et al, 2019). 
2.6.2. 
Dose Rationale 
Pamrevlumab has been tested in a Phase 1 single-ascending dose study (FGCL-MC3019-002) 
and two repeat-dose Phase 2 studies (Study 049 and Study 067) in IPF patients. The single-dose 
study utilized intravenous infusions of 1, 3, or 10 mg/kg. Study 049 was an open-label study 
testing 15 mg/kg and 30 mg/kg every 3 weeks for 45 weeks as monotherapy. Study 067 was a 
placebo-controlled study testing 30 mg/kg every 3 weeks for 45 weeks as monotherapy. All 
studies collected safety and tolerability data, samples for pharmacokinetic analyses and 
pulmonary function test measurements. 
Prior to studying IPF, pamrevlumab was tested in a Phase 1 multiple ascending dose study in 
combination with gemcitabine and erlotinib in advanced pancreatic cancer patients using IV 
doses of 3 mg/kg up to 45 mg/kg every 2 weeks, and weekly doses up to 22.5 mg/kg. The Phase 
1 study in pancreatic cancer included assessments of safety and tolerability, samples for 
pharmacokinetic analyses and measures of disease progression.  
Collectively these studies have investigated repeat doses up to 30 mg/kg every three weeks in 
IPF and up to 45 mg/kg every 2 weeks in pancreatic cancer. The doses in all studies were found 
to be safe and tolerable and active doses were identified in each indication.   
The combined data were analyzed via population pharmacokinetics (PopPK) to determine if the 
PK for the two indications were similar. The combined PopPK model was used to derive steady 
state trough exposures of pamrevlumab leading to exposure-response relationships for the two 
Phase 2 IPF studies. The efficacy measure was forced vital capacity FVCpp. Clinical trial 
simulations of FVCpp were also performed to evaluate the probability of success of 


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pamrevlumab versus placebo at different doses. Safety data for the two Phase 2 IPF studies were 
tabulated by dose group, and exposure-response relationships were explored for selected adverse 
events. These analyses form the basis for the Phase 3 dose in IPF patients and shows that an IV 
administration of 30 mg/kg of pamrevlumab every three weeks to IPF patients achieves better 
efficacy than placebo for FVCpp, and reaches the mean pamrevlumab trough where efficacy 
begins to plateau (approximately 150 µg/mL). 
2.6.3. 
Safety Summary, and Benefit – Risk Assessment 
Overall, pamrevlumab has been well-tolerated. 
Three Phase 1/2 studies were completed in IPF: Study FGCL-MC3019-002(N=21); Study 
FGCL-3019-049(N=89; 53 receiving 15mg/kg and 36 receiving 30mg/kg pamrevlumab); and 
Study FGCL 3019-067(N=103; 50 randomized to pamrevlumab 30mg/kg, 53 randomized to 
placebo). The majority of TEAEs reported were of respiratory nature and consistent with those 
reported for historical, comparable IPF populations (Richeldi, 2014). Across the IPF studies, the 
most common treatment emergent adverse event (TEAEs) by subject have been cough, fatigue, 
dyspnea, upper respiratory tract infection, bronchitis, and nasopharyngitis. 
In study FGCL-MC3019-002, pamrevlumab was well tolerated across the range of doses studied; 
there were no dose-limiting toxicities, and adverse events were generally mild or moderate. A 
single TESAE, interstitial lung disease in the 10 mg/kg dose cohort, was reported during the 
study. No subject withdrew due to a TEAE.  
During a post-PK long term follow up three subjects died: approximately two, six, and 11 
months after the administration of pamrevlumab, respectively, due to disease progression. None 
of the deaths were considered related to pamrevlumab. 
In study FGCL-3019-049, the most frequent TEAEs were cough, fatigue, dyspnea, upper 
respiratory tract infection and bronchitis, which are consistent with those AEs reported for 
historical, untreated controls in IPF populations in randomized, placebo-controlled studies  
(King 2009; Raghu et al, 2004; Zisman et al, 2010; King et al, 2014; Richeldi et al, 2014). 
TEAEs were similar across cohorts and also similar when comparing these observed during the 
initial 48 weeks and during the extension. Approximately one-third of study subjects experienced 
TEAEs Grade ≥3 and these were of respiratory nature, related to IPF or its complications. 
TESAEs were reported in about one-third of subjects, mainly related to IPF or its complications. 
Treatment or study discontinuation was reported for 16 subjects, the most frequent cause being 
IPF progression. A total of 13 deaths have been reported during the entire study duration 
(including the first 48 weeks and the extension periods), 12 of them from respiratory causes. The 
mortality rate observed in this study is below the calculated expected mortality rate as per the 
GAP system (Ley et al, 2012). 
In Study FGCL 3019-067, pamrevlumab was well tolerated, with a safety profile similar to that 
of placebo: 48 (96%) patients, in the pamrevlumab group compared to 52 (98%) patients in the 
placebo group had at least one TEAE. TESAEs were observed in 12 patients (24%) in the 
pamrevlumab group and 8 (15%) in the placebo group and were mostly respiratory-related; 
however, fewer patients in the pamrevlumab group discontinued study treatment because of a 
TESAE than did those in the placebo group: three (6%) versus seven (13%), and fewer patients 
in the pamrevlumab group five [10%]) compared to placebo (seven [13%]) were hospitalized 


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following a respiratory-related TESAE. Nine patients died during the study: three (6%) in the 
pamrevlumab group and six (11%) in the placebo group. No safety concerns were identified in 
the analysis of clinical laboratory results or ECG parameters.   
Regarding efficacy results in study 067, subjects receiving pamrevlumab showed a statistically 
significant difference from placebo for the primary efficacy endpoint of FVCpp change from 
baseline to week 48 favoring pamrevlumab. In addition, other efficacy results showed that 
pamrevlumab slowed the progression of IPF as measured by change in HRCT quantitative lung 
fibrosis, and time to disease progression as measured by 10% categorical decline in FVCpp or 
death. 
In summary, across all completed phase 2 IPF studies, the observed TEAEs have been generally 
mild or moderate in severity and transient in duration, have been typical of the patients’ 
underlying medical condition(s) and, in the placebo-controlled study, were equally distributed 
between the placebo and pamrevlumab treatment groups.  
Therefore, based on the cumulative safety data and the potential benefit of pamrevlumab in IPF, 
the benefit/risk profile is considered overall favorable (Wells, 2019). 
 


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3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Objective 
The overall objective of this trial is to evaluate the efficacy and safety of 30 mg/kg IV infusions 
of pamrevlumab as compared to placebo in subjects with Idiopathic Pulmonary Fibrosis.   
3.2. 
Endpoints 
3.2.1. 
Primary Endpoint:  
• Change in FVC (L) from baseline at Week 48 
3.2.2. 
Secondary Endpoints 
• Time to disease progression, defined as absolute FVC percent predicted (FVCpp) 
decline of ≥10% or death, whichever occurs first 
• Change in Quantitative Lung Fibrosis (QLF) volume from baseline at Week 48  
• Time to any component of the clinical composite endpoint, whichever occurs first: 
acute IPF exacerbation, respiratory hospitalization, or death  
• Time to first acute IPF exacerbation during study    
• Time to all-cause mortality during study 
• Time to first respiratory hospitalizations during study 
 
3.2.3. 
Exploratory Endpoints 
Exploratory endpoints include:  
• Time to composite of: respiratory hospitalization or death or absolute FVCpp decline 
≥10%, whichever occurs first  
• Change in absolute FVCpp from baseline at Week 48  
• Change in relative FVCpp from baseline at Week 48  
• Change in St. George’s Respiratory Questionnaire (SGRQ) score from baseline at 
Week 48  
• Change in University of California San Diego – Shortness of Breath Questionnaire 
(UCSD-SOBQ) score from baseline at Week 48  
• Change in Leicester Cough Questionnaire (LCQ) from baseline at Week 48  
• Exploratory biomarkers  
 
3.2.4. 
Safety Assessment  
Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events 
(TESAEs), clinical laboratory parameters, vital signs, immunogenicity (Human Anti-Human 
Antibody [HAHA] formation), and hypersensitivity/anaphylactic reactions.  


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3.3. 
Overall Study Design 
This is a Phase 3, randomized, double-blind, placebo-controlled multi-center trial to evaluate the 
efficacy and safety of pamrevlumab in subjects with IPF. Approximately 340 subjects will be 
enrolled in this trial.   
Subjects must be fully informed of the potential benefits of approved products and make an 
informed decision that they prefer to participate in a clinical trial in which they could be 
randomized to placebo. 
NOTE: Plans to re-screen a subject must be discussed with and approved by the Medical 
Monitor, prior to re-screening 
Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms:  
Arm A: pamrevlumab, 30 mg/kg IV, Day 1 and every 3 weeks thereafter 
Arm B: Matching placebo IV, Day 1 and every 3 weeks thereafter  
Subjects will be stratified at randomization by GAP stage (I, II, III) derived from the GAP score 
obtained during screening (See Appendix 5).  NOTE:  For calculation of the GAP score: Use the 
Best-Test Review (BTR) assessment provided by the spirometry vendor over-reader of the 
screening value (See Section 6.2.5 and Appendix 5) 
This study consists of the following study phases: 
• Main (double blind, placebo-controlled) phase:  
o Screening period: Up to 6 weeks 
o Treatment period: 48 weeks  
• Optional, open label extension phase:  
o Access to pamrevlumab will be available until the last subject completes 48 
weeks of treatment in the OLE phase, or pamrevlumab is commercially available 
for the indication of IPF, or the Sponsor decides to end the OLE phase, whichever 
occurs first 
• Follow-up period/final safety assessment:  
o 28 days after last dose: safety follow-up visit 
o 60 days after last dose: follow-up phone call, for a final safety assessment   
Note: These two final safety assessments are to be scheduled after the last, final dose 
of study drug (e.g.: for subjects not progressing to the optional OLE phase, the last 
dose is the last dose  received in the double blind phase; for subjects continuing in the 
OLE phase, the last dose is the last dose received in the OLE phase.)  
The intent of this study is to evaluate the efficacy and safety profile of pamrevlumab as 
monotherapy in subjects with IPF who had previously been treated with an approved therapy but 
who discontinued that therapy (possible reasons for discontinuation of approved therapy could 
include, but are not limited to, intolerance or disease progression), unless neither treatment is 
available in the host country.  


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NOTE: No subject should discontinue an approved therapy for the purpose of enrolling in this 
study. 
During the treatment period, co-administration of one of the two approved IPF therapies, 
pirfenidone or nintedanib, is acceptable if clinically indicated in the Investigator’s opinion, after 
assessment of potential risks / benefits of such combination with blinded study treatment. 
However, since subjects either tried an approved IPF therapy prior to study participation, or have 
no such treatment available, it is not expected that many subjects will resume treatment with an 
approved IPF therapy during this study. See also Section 5.1.10. 
A schematic overview of the study is provided in Figure 1. A detailed overview of assessments 
and the timing of assessments is provided in Appendix 1. A detailed overview of the OLE 
assessments and procedures is provided in Appendix 6. 
3.3.1. 
Study Duration 
Subjects are encouraged to receive all 17 study drug doses in the main study. Subjects who do 
not receive all doses are encouraged to continue with study visits and assessments. 
Subjects who complete the Week 48 visit (regardless of the number of study drug doses 
received) will be eligible for an open-label, extension (OLE) phase, which will provide 
continuing access to pamrevlumab until the last subject completes 48 weeks of treatment in the 
OLE phase, or pamrevlumab is commercially available for the indication of IPF, or the Sponsor 
decides to end the OLE phase, whichever occurs first.  
Subjects who withdraw from the main study early, for any reason, will have an Early Study 
Termination visit (ET) as soon as feasible. Study procedures to be performed during the ET visit 
can be found in the SOA (Appendix 1). These subjects will also have a safety follow up visit 28 
days after the last dose, with a follow-up phone call 60 days after the last dose for a final safety 
assessment. Such subjects should also be contacted by phone at weeks 24 and 48 to check the 
subject’s vital status. These subjects will not be eligible for the OLE phase  
See also Section 4.3 for mandatory Study Withdrawal reasons, and Section 4.4 for procedures 
related to Early Study Withdrawal. 


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Figure 1: 
FGCL-3019-095 Study Schema 
 
 
3.3.2. 
Placebo Control Group 
In order to evaluate the effect of treatment with pamrevlumab on the endpoints described in 
Section 3.2 50% of subjects will be randomized to placebo treatment. 
A placebo control is appropriate and ethical for this trial given the intended population of 
participating subjects: those who have not responded to or are intolerant of approved IPF 
therapies. For these subjects the best treatment option is supportive care, which is available to 
them within this protocol. In addition, they have the option of receiving treatment with an 
approved IPF therapy any time after randomization, if clinically indicated in the Investigators 
opinion, without the need to end study participation.  All study subjects who complete the Week 
48 visit (regardless of the number of study drug infusions received) will be offered participation 
in the optional OLE phase which provides continuing access to pamrevlumab treatment 
(Appendix 6). NOTE: No unblinding of subject’s treatment assignment in the main study will 
occur for purposes of OLE participation 
3.4. 
Randomization and Treatment Assignment 
3.4.1. 
Randomization  
Approximately 340 subjects will be randomized 1:1 to receive either pamrevlumab or placebo, 
resulting in approximately 170 subjects per treatment arm.  Each subject will receive a unique 
study ID number during screening.   
Subjects will be stratified at randomization according to GAP stages (I, II, III), derived from the 
GAP score obtained during screening (See Section 6.2.5 and Appendix 5).  Automated 
randomization and treatment assignments will be performed by an Interactive Response System 
(IXRS or IRT).   
3.4.2. 
Treatment Assignment 
Subjects will be randomized 1:1 to one of two treatment arms: 
Arm A: Pamrevlumab 
Arm B: Placebo 


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3.5. 
Blinding 
This is a double-blind, placebo-controlled study. The Investigator, study site staff, subjects, 
selected Sponsor clinical team and designees are blinded to study drug assignment. Blinded 
treatment with a placebo control is the gold standard method for obtaining unbiased assessments 
of safety and efficacy in clinical trials of investigational drugs such as pamrevlumab. 
3.5.1. 
Maintenance of Blinding 
The study blind will be maintained for all parties specified above throughout the study with the 
exception of the scenarios outlined in Section 3.5.2. Pamrevlumab and placebo are identical in 
appearance, packaging, and labeling in order to maintain the study blind.   
3.5.2. 
Request for Unblinding of Treatment Assignment 
Breaking the blind during the study (for a single subject) should be considered only when 
knowledge of the treatment assignment is deemed essential by the Investigator due to immediate 
safety concerns, or is considered essential for the immediate subject management. The 
responsibility to break the blind (for a single subject) in emergency situations resides solely with 
the Investigator.  It is the Investigator’s responsibility to promptly document and explain any 
unblinding to the Sponsor.   
Such emergency unblinding will be done by the Investigator using the automated Interactive 
Response System (IXRS or IRT) which ensures rapid unblinding in emergency situations. 


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4. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1. 
Subject Inclusion Criteria 
In order to be eligible for inclusion in this trial, a subject must meet all of the following: 
1. Age 40 to 85 years, inclusive, at screening initiation. 
2. Diagnosis of IPF as defined by ATS/ERS/JRS/ALAT guidelines (Raghu 2018).  
3. IPF diagnosis within the past 7 years, with onset defined as the date of the first recorded 
diagnosis of IPF by HRCT and/or surgical lung biopsy (SLB), or other appropriate tissue 
sample (e.g., cryobiopsy) in the medical history. 
4. Interstitial pulmonary fibrosis defined by HRCT scan at screening, with evidence of 
≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing, within the 
whole lung. NOTE: this requires confirmation by an Independent Radiology Imaging 
Review Group, prior to randomization. If a recent HRCT scan (within 3 months prior to 
screening) is available, it can be utilized for screening purposes, provided it is submitted 
and evaluated by the Independent Radiology Imaging Review Group, is adhering to the 
same imaging acquisition parameters detailed in the Imaging Core Manual (ICM), and is 
either using the same accredited scanner, or is performed using the same modality, as the 
on-study HRCT scans. 
5. FVCpp value >45% and <95% at Screening and Day 1(prior to randomization).  
6. Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted and 
corrected by Hb value ≥25% and ≤90% at screening (determined locally). If a DLCO is 
available within 3 months prior to screening, it can be utilized for screening purposes 
7. Both FVC and DLCO testing must be representative of the IPF underlying disease (i.e. 
have been obtained in absence of an acute respiratory event [e.g. lung infection, cold] or 
other events that are known to affect PFT testing results [e.g., broken rib, chest pain, 
other]). 
8. Previously treated with an approved IPF therapy (i.e., pirfenidone or nintedanib) but 
discontinued at least 1 week prior to screening, unless neither treatment is available in the 
host country. NOTE: no subject should discontinue approved therapy for the purpose of 
enrolling in this study.  


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9. Male subjects with partners of childbearing potential and female subjects of childbearing 
potential (including those <1 year postmenopausal) must use a highly effective method of 
contraception per Clinical Trial Facilitation Group (CTFG) recommendation (see 
protocol section 5.2.3 for details) during the conduct of the study, and for 3 months after 
the last dose of study drug.  Women not of childbearing potential are defined as: 
a. Post-menopausal; women (defined as at least 12 months with no menses without an 
alternative medical cause); in women < 45 years of age, a high follicle stimulating 
hormone (FSH) level in the post-menopausal range may be used to confirm a post-
menopausal state in women not using hormonal contraception or hormonal 
replacement therapy. OR 
b. Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or 
bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR 
c. Have a congenital or acquired condition that prevents childbearing. 
10. Able to understand and sign a written informed consent form. 
4.2. 
Subject Exclusion Criteria 
Subjects will be ineligible for and excluded from this trial if any of the following apply:  
1. Previous exposure to pamrevlumab. 
2. Evidence of significant obstructive lung disease by any of the following criteria: (1) 
forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio <0.70, or 
(2) extent of emphysema greater than the extent of fibrosis on HRCT. NOTE: this 
requires confirmation by an Independent Radiology Imaging Review Group, prior to 
randomization. 
3. Female subjects who are pregnant or nursing. 
4. Smoking within 3 months of screening and/or unwilling to avoid smoking throughout the 
study. 
5. Interstitial lung disease (ILD) other than IPF, including but not limited to any of the other 
types of idiopathic interstitial pneumonias; lung diseases related to exposure to fibrogenic 
agents or other environmental toxins or drugs; other types of occupational lung diseases; 
granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including 
vasculitis, infectious diseases and connective tissue diseases. In cases of uncertain 
diagnosis, serological testing and/or review by multi-disciplinary team should be 
performed to confirm diagnosis of IPF vs. other types of ILD. 
6. Sustained improvement in the severity of IPF during the 12 months prior to screening, 
based on changes in FVC, DLCO, and/or HRCT scans of the chest. 
7. History of other types of respiratory diseases, including diseases or disorders of the 
airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall that, in 
the opinion of the Investigator, would impact the primary protocol endpoint or otherwise 
preclude the subject’s participation in the study. 


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8. Medical conditions (e.g. MI/stroke within the past 6 month), or logistical challenges that 
in the opinion of the Investigator preclude the subject’s adequate participation in the 
study. 
9. Poorly controlled chronic heart failure (NYHA Class 3 or above); clinical diagnosis of 
cor pulmonale requiring specific treatment; or severe pulmonary arterial hypertension 
requiring specific treatment that, in the opinion of the Investigator, would preclude the 
subject’s participation in the study.  
10. Clinically important abnormal laboratory tests (including serum creatinine ≥1.5 x upper 
limit of normal [ULN], hemoglobin (Hb) <10 g/dL, white blood cells <3,000/mm3, 
platelets less than 100,000/mm3, serum total bilirubin >1.5 x ULN, serum alanine 
aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 x ULN, or serum 
alkaline phosphatase ≥2 x ULN. 
11. Ongoing acute IPF exacerbation, or suspicion of such process during screening or 
randomization, including hospitalization due to acute IPF exacerbation within 4 weeks 
prior to or during screening. 
12. High likelihood of lung transplantation (in the opinion of the Investigator) within 6 
months after Day 1. 
13. Use of any investigational drugs or unapproved therapies, or participation in any clinical 
trial with an investigational new drug within 30 days prior to screening. 
14. Daily use of PDE-5 inhibitor drugs (e.g. sildenafil, tadalafil), except for treatment of 
severe pulmonary artery hypertension. 
15. Any current malignancy (this does not include localized cancer such as basal or 
squamous cell carcinoma of skin).  Any history of malignancy likely to result in 
mortality, or requiring significant medical or surgical intervention within the next year.  
16. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies, or to any component of the excipient. 
17. Any condition (other than IPF) that is likely to result in the death of the patient within the 
next year. 
18. Acute infection requiring any of the following: 
a. Hospital admission for ≥24 hours within four weeks prior to screening, or during 
screening 
b. Treatment with antibiotics (IV, IM, oral, or inhaled) within four weeks prior to 
screening, or during screening 
c. Active or recent (≤4 weeks prior to randomization) upper or lower respiratory tract 
infection 
d. Active tuberculosis requiring treatment within 12 months prior to screening 
19. Known history of immunodeficiency, including but not limited to HIV infection 
20. Receipt of a live/attenuated vaccine within the four weeks prior to randomization 


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21. Chronic treatment with any of the following within four weeks or five half-lives 
(whichever is longer) prior to randomization, if used to treat IPF: 
a. Immunosuppressive or immunomodulatory therapies (e.g., azathioprine, cyclosporine 
A, cyclophosphamide, D-penicillamine, interferon-gamma, tumor necrosis factor- α 
antagonists) 
b. Cytotoxic drugs (e.g., colchicine) 
22. The Investigator judges that the subject will be unable to fully participate in the study and 
complete it for any reason, including inability to comply with study procedures and 
treatment, addiction, or any other relevant medical or psychiatric conditions. 
23. Country Specific Criteria (Czech Republic Only): Positive result from a Tuberculosis 
(TB) screening test performed within 6 months prior to screening for the study. TB 
testing may be done locally. 
4.3. 
Subject Study Withdrawal Criteria 
Subjects who do not receive all study drug doses in the main study are encouraged to remain in 
the study and continue with the regular study visits and assessments. However, subjects may 
withdraw from the study at any time, for any reason. Reasons for discontinuing study drug 
treatment, as well as reasons for withdrawing from study, will be captured on CRF. 
Mandatory reasons for withdrawing the subject from the study include the following:  
• Any safety concern in the Investigator’s opinion, that precludes further study 
participation, including infusion-associated reactions deemed life-threatening by the 
Investigator (see also/ Section 5.1.6) 
• Lung transplant 
• Pregnancy 
• Major protocol deviation that substantially affects subject safety or assessment of 
efficacy endpoints  
• Withdrawal of Consent 
4.4. 
Subject Study Withdrawal Procedures/Assessments 
Subjects who terminate / withdraw from the study early, for any reason, will have an Early Study 
Termination (ET) visit as soon as feasible. Study procedures to be performed during the ET visit 
can be found in the SOA (Appendix 1). At the ET visit, PFTs and questionnaires do not have to 
be repeated, if the last one (excluding screening visit) was performed within 8 weeks of this visit; 
HRCT does not have to be repeated, if the last one (excluding the screening visit) was performed 
within 4 months of this visit.  
These subjects will have a safety follow-up visit 28 days after the last dose. A follow-up phone 
call 60 days after last dose will also be completed for a final assessment of safety. 
In addition, these subjects should be contacted by phone for vital status at weeks 24 and 48. 
These subjects will not be eligible for the OLE phase. 


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4.5. 
Replacement of Study Subjects 
All randomized subjects will be included in the study. Subjects who terminate the study early 
will not be replaced.  
4.6. 
Study Closure 
FibroGen reserves the right to close any investigational site(s) or terminate the study at any time 
for any reason.  Reasons for the closure of the study site or termination of the study by FibroGen 
may include (but are not limited to): 
• Successful completion of the study at the investigational site 
• The required number of subjects for the study has been recruited 
• Failure of the Investigator to comply with the protocol, GCP guidelines or local 
requirements 
• Safety concerns 
• Inadequate recruitment of subjects by the Investigator  


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5. 
TREATMENT OF SUBJECTS 
5.1. 
Study Treatment 
5.1.1. 
Pamrevlumab or Placebo 
Pamrevlumab is a fully human IgG1 kappa monoclonal antibody that binds to CTGF and is 
formulated as solution for administration by IV infusion. 
Matching placebo is formulated as solution to be administered in a manner that is identical to 
pamrevlumab infusion. 
5.1.2. 
Formulation 
Pamrevlumab is supplied in single-use glass vials containing sterile, preservative-free solution 
(100 mg pamrevlumab/vial or 500 mg pamrevlumab/vial respectively).  The solution is 
composed of 10 mg/mL pamrevlumab, 1.60 mg/mL L-histidine, 3.08 mg/mL L-histidine HCl, 
8.01 mg/mL sodium chloride, and 0.05 mg/mL polysorbate 20, resulting in a solution with a 
tonicity of approximately 290 mmol/kg and a pH of 6.0.   
The placebo formulation is of identical composition as the pamrevlumab formulation, except for 
the absence of pamrevlumab. 
5.1.3. 
Study Drug Packaging and Labeling 
Labels will be prepared and will comply with Good Manufacturing Practice requirements for 
labelling and local regulatory guidelines.   
5.1.4. 
Study Drug Storage 
All Investigational Product (IP) vials must be stored refrigerated (2°C to 8°C), in a temperature- 
controlled and monitored environment, protected from light, and in a securely locked area to 
which access is limited to appropriate study personnel. Documentation of the storage conditions 
must be maintained by the site for the entire period of study participation. Details regarding the 
reporting of temperature excursions can be found in the study Investigational Product (IP) 
Manual. 
5.1.5. 
Study Drug Preparation 
IP is infused undiluted after pooling the contents of the calculated number of vials in an empty 
infusion bag according to the Dose Preparation Instructions in the IP Manual. 
Once prepared, the IP for infusion is stable at room temperature for up to 6 hours. However, if 
prepared IP is stored refrigerated at 2˚C to 8˚C, the IP is stable for 48 hours.  
IP is administered by IV infusion, using an infusion set with a 0.2 µm in-line filter. 
5.1.6. 
Study Drug Administration 
Dosing is based on the weight obtained on Day 1 and every 12-weeks thereafter. The total dose 
is not to exceed 4.1g.  The total volume of fluid is not to exceed 410 mL. Study Drug is 
administered by IV infusion, using an infusion set with a sterile, nonpyrogenic, low-protein-


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binding in-line filter (0.2-micron pore size). The infusion and post-infusion observation periods 
are provided in Table 1 below. 
Table 1 
Pamrevlumab (or placebo): Dose, Route, and Administration 
Agent 
Dose 
Route 
Infusion Rate 
Frequency 
Pamrevlumab/ 
matching placebo 
30 mg/kg 
IV 
• 
First Infusion (including first infusion in 
OLE) : Infuse over approximately 2 
hours.   
• 
Second Infusion (including second 
infusion in OLE): If first infusion is well 
tolerated, infuse over approximately 1 
hour.  
• 
Subsequent Infusions: If 1 hour 
infusion(s) are well tolerated, infuse over 
approximately 30 minutes. 
 
For ALL infusions: A Post-infusion 
observation period has to be included 
throughout the study: It is 1 hour for at least 
the first 3 infusions (including in OLE); this 
may be reduced to 30 minutes if there were no 
infusion-related AEs after the first 3 infusions. 
For Czech Republic only: A Post-infusion 
observation period has to be included 
throughout the study:  2 hours for the first 3 
infusions; this may be reduced to 30 minutes 
if there were no infusion-related AEs after the 
first 3 infusions 
Day 1 and 
Every 3 
weeks 
thereafter 
 
NOTE: 
Infusions 
must be AT 
LEAST 10 
days apart 
NOTE:  DO NOT ADMINSITER STUDY DRUG AS AN IV PUSH OR BOLUS INJECTION, OR 
CONCURRENTLY IN THE IV LINE WITH OTHER AGENTS. 
The first infusion should be completed in approximately 2 hours. If the first infusion is well 
tolerated and no infusion-associated AEs are observed during the infusion and observation 
period, the second infusion should be completed in approximately 1 hour. The subsequent 
infusion periods may be shortened to approximately 30 minutes, if no infusion-associated AEs 
were observed during the initial two infusions.  
If an infusion-associated AE occurs during any of the subsequent infusions, study drug will be 
administered over approximately 1 hour for the next three infusions. If no infusion associated 
AEs are observed in any of these three infusions, the infusion may be decreased again to 
approximately 30 minutes. 
The Investigator or other qualified personnel must be either present, or immediately available, 
during all infusions and observation periods for each subject. If a subject has a significant 
infusion associated AE, the infusion rate may be slowed or temporarily stopped, depending on 
the severity of symptoms. If such a subject continues study drug dosing, a physician should be 
immediately available during all subsequent infusions and observation periods at the site.  
Subjects who experience an infusion associated AE will not be allowed to participate in Home 
Health Care (HHC). In addition, if a subject experiences a life-threatening (per Section 7.3.3) 
infusion-associated AE, study drug treatment must be permanently discontinued  
(see Section 4.3).  


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 The Investigator has the option to use premedication, e.g., antihistamines, nonsteroidal anti-
inflammatory drugs (NSAIDs) for a subsequent infusion: this may be discussed with the 
FibroGen Medical Monitor or designee.  
Infusions are to be continued until the total volume has been administered. Subjects will remain 
at the study site for 1 hour (2 hours for Czech Republic Only) after the end of the infusion for 
clinical observation. This post-infusion observation period may be reduced to 30 minutes if the 
subject has had no infusion-associated AEs during the first three infusions. 
Study drug will be administered at a hospital or ambulatory setting with adequate facilities for 
managing medical emergencies. Medications for the treatment of acute reactions, including 
anaphylaxis, must be available to study site staff for immediate use. There is no specific 
treatment for a pamrevlumab overdose or infusion-associated AEs. Signs and symptoms should 
be managed with appropriate standard of care treatment. 
The Sponsor may consider the use of properly trained home health care staff to administer the 
infusions of study drugs at the subject’s home and corresponding study assessments during the 
conduct of the study (after the completion of at least three 30-minute infusions without safety 
concerns), consistent with institutional regulations and policies. See Section 5.1.7 for details. 
COVID-19 Vaccine and Study Drug Administration 
If a subject receives a COVID-19 vaccine during the study, it is recommended that a time 
separation of at least 48 hours is maintained between administration of the COVID-19 vaccine 
(single/multiple dose) and study drug infusion. The time separation may allow for better 
interpretation of any adverse events and their relationship to the vaccine or study drug.  
The following procedures must be performed prior to each infusion: 
• Vital signs (blood pressure [BP], pulse, and temperature) within 30 minutes before  
starting the infusion 
• Query subject and assess AEs and SAEs 
• Record concomitant medications 
The following procedures must be performed after each infusion: 
• Vital signs (BP, pulse, and temperature) within 30 minutes after completion of the 
infusion  
• Query subject and assess AEs and SAE’s 
5.1.7. 
Home Health Care 
The Sponsor may consider the use of properly trained and qualified home health care staff in 
specific regions/countries, depending on local acceptance and adoption of home visits, to 
administer study drug at the subject’s home, after completion of at least the first three infusions 
without safety concerns.  Home Health Care (HHC) is optional and the decision to utilize this 
service is determined by the site, consistent with institutional regulations and policies.  
NOTE: Subjects who experience a significant infusion-associated AE may not receive HHC. In 
addition, if a new safety concern arises during a home infusion, the subject has to attend an on-
site visit for an Investigator assessment as soon as feasible. HHC support will only be on weeks 


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with study drug infusions and no scheduled study assessments. Visits that include collection of 
PFT, ePRO, safety labs or HRCT must be performed on-site. Medications and supplies to treat 
suspected hypersensitivity/anaphylactic reactions must be available for immediate use for all study 
drug infusion visits. 
5.1.8. 
Missed Dose 
Every attempt should be made to complete all study visits within the windows as outlined in the 
Schedule of Assessment (SOA) (Appendix 1).  
Scheduled visit dates are determined from the time of the first dose, which is defined as Day 1. A 
visit schedule is provided in Section 6.1.2 and the SOA (Appendix 1). Visits conducted outside 
the visit windows will be recorded as a protocol deviation. Missed doses are not to be made up 
through extra visits. If a subject misses more than two infusions in any 18-week period 
throughout the study, or two sequential infusions, the FibroGen Medical Monitor should be 
notified.  The reason for missed doses must be documented in the subject’s clinical record. 
If a dose is missed due to a missed visit, see section 6.1.4 and 6.1.5. 
Refer to the case report form (CRF) completion guidelines for additional information on CRF 
completion requirements for missed visits.  
5.1.9. 
Study Drug Handling and Disposal 
All study drug provided by the Sponsor should be retained at the site until otherwise instructed in 
writing by the Sponsor (or designee). If local/regional/institutional policies do not allow the site 
to retain study drug, the site must provide the Sponsor (or designee) their drug destruction 
SOP/process for review and approval. The Sponsor (or designee) will perform drug 
accountability and reconciliation for all study drug received at the site prior to approving study 
drug return/destruction. Upon completion of accountability/reconciliation or upon completion of 
the study or termination of the investigational site, all used, unused, partially used study drug, 
and all study drug that was not dispensed will be shipped to a destruction site designated by the 
Sponsor (or designee) for destruction. IV bags used to infuse study drug can be disposed of per 
institutional policy. Please refer to the IP Manual for additional information on study drug 
materials, management and accountability.   
5.1.10. 
Co-Administration of an Approved IPF Therapy  
During the treatment period, co-administration of an approved IPF therapy (i.e., pirfenidone or 
nintedanib) is acceptable if clinically indicated in the Investigator’s opinion, provided that the 
Investigator assesses the potential risks/benefits of combining approved IPF therapies with 
blinded study treatment. 
Dosing of approved IPF therapy, and safety monitoring while receiving such therapy, must be in 
accordance with the approved therapy’s local label. 
5.1.11. 
Treatment Compliance 
All treatments are administered at the investigational site by qualified personnel and documented 
in the corresponding case report form (CRF). 


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5.2. 
Concomitant Medications 
5.2.1. 
Permitted Concomitant Medications 
Concomitant medications (any prescription and/or over-the-counter [OTC] preparation) and 
procedures or nondrug therapies (e.g., physical therapy, acupuncture, continuous positive airway 
pressure [CPAP]) used by a subject while participating in this clinical trial must be recorded 
from the Screening Visit through 28 days after the last dose. If the subject experiences an AE or 
SAE before the end of the final safety phone call (60 days after last dose), concomitant 
medications and nondrug therapies may also be collected, if part of the treatment of the AE/SAE.   
Other than the restrictions that follow, concomitant medications may be given at the discretion of 
the Investigator. It is expected that Investigators will provide optimal medical care for the 
subject’s various co-existing medical conditions. The Investigator should ensure optimal medical 
care is provided the course of the study. 
Oral prednisone or equivalent oral corticosteroid: up to 10 mg daily for chronic use is permitted, 
as long as such use is for a condition other than IPF,and has to be documented accordingly. 
Higher doses for acute conditions are permitted.  N-acetylcysteine (NAC): up to 1800 mg daily, 
is also permitted during the study. 
COVID-19 vaccination is permitted during the study. Refer to section 5.1.6 for additional details, 
for the recommended timing between COVID-19 vaccinations and study drug dosing. 
5.2.2. 
Prohibited Concomitant Medications 
Pirfenidone and nintedanib are permitted as approved IPF therapies, if clinically indicated during 
the study. For details, see Section 5.1.10. 
Prohibited medications include any other (off-label or investigational) agents for the treatment of 
interstitial lung diseases including IPF. The list of prohibited concomitant medications for 
treatment of IPF includes, but is not limited to, the following:  
• sildenafil: if  used for erectile dysfunction the frequency of administration should be 
no more than two times a week,  
• azathioprine,  
• cyclophosphamide,  
• cyclosporine,  
• interferon gamma 1b,  
• D penicillamine,  
• methotrexate,  
• leflunomide,  
• colchicine,  
• bosentan,  
• ambrisentan,  


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• aminobenzoate,  
• mycophenolate mofetil,  
• imatinib,  
• relaxin,  
• etanercept,  
• adalimumab,  
• infliximab,  
• anakinra,  
• abatacept,  
• rituximab  
If any of these treatments are prescribed for their approved indications, for other co-existing 
medical conditions such as systemic inflammatory diseases (e.g., rheumatoid arthritis, severe 
pulmonary hypertension, etc.), such uses are allowed. All indication needs to be clearly 
documented in the subject’s clinical record. 
Questions about concomitant medications should be discussed with the FibroGen Medical 
Monitor. 
5.2.3. 
Contraception Requirements  
A non-clinical study evaluating the potential effects of pamrevlumab on embryo-fetal development 
has been conducted (rabbit embryo-fetal development study 352021017). The pamrevlumab systemic 
exposure levels at 200 mg/kg to the pregnant female rabbits which resulted in fetal external and 
skeletal abnormalities are approximately 20-fold greater than the systemic exposure levels in humans 
at doses of 30 mg/kg or 35 mg/kg in our current protocols. 
No adverse effects of pamrevlumab administration were observed in a study of rat male and 
female fertility. Lacking information from clinical studies, female subjects of childbearing 
potential and male subjects who have partners with reproductive potential are required to use a 
highly effective method of contraception per Clinical Trial Facilitation Group (CTFG) 
recommendation (for reference see section 13) during the  study and for 3 months after the last 
dose of study drug as follows : 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1:  
- oral  
- intravaginal  
- transdermal  


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• Progestogen-only hormonal contraception associated with inhibition of ovulation1:  
- oral  
- injectable  
- implantable2  
• Intrauterine device (IUD)2  
• Intrauterine hormone-releasing system (IUS)2  
• Bilateral tubal occlusion2  
• Vasectomised partner2,3  
• Sexual abstinence4  
In each case of delayed menstrual period (over one month between menstruations) confirmation of 
absence of pregnancy is strongly recommended. This recommendation also applies to women of 
childbearing potential with infrequent or irregular menstrual cycles. 
1Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method (see section 4.3 of the CTGF guidance document).  
2Contraception methods that in the context of the CTGF guidance are considered to have low user dependency.  
3Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of 
the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical 
success.  
4In the context of the CTGF guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred 
and usual lifestyle of the subject. 
  


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6. 
ASSESSMENTS OF EFFICACY 
6.1. 
Study Assessments 
A signed and dated IRB/IEC-approved informed consent must be obtained before any study-
specific assessments are performed. Assessments that are part of routine care are not considered 
study-specific and may be used at screening to determine eligibility. All subjects will be 
screened for eligibility before randomization. Only eligible subjects will be randomized into the 
study.  
6.1.1. 
Screening Period 
All screening procedures must be performed within 6 weeks.  Plans to rescreen a subject should 
be discussed with the medical monitor.. Study procedures to be performed during the screening 
period can be found in the SOA (Appendix 1).   
6.1.2. 
Treatment Period 
The study procedures and assessments are presented for the Treatment phase in Appendix 1. 
The treatment period begins on Day 1 (first study drug infusion) and continues through Week 48. 
Visit windows are within ±7 days of the scheduled visit date for Weeks 3 through 48; however, 
visits should be at least 10 days apart, to ensure intervals of at least 10 days between study drug 
infusions. The visit window of ±7 days also applies to assessments that cannot be performed on 
the same day; these assessments are considered part of that specific visit, and are to be labelled 
as such. 
Subjects who complete the Week 48 visit may be eligible to participate in an optional OLE 
period where all subjects are offered continuing access to pamrevlumab treatment. The details of 
procedures and assessments, including visit window for OLE are described in Appendix 6.   
6.1.3. 
Safety Follow-Up 
Safety assessments will be performed at the following two time points: 
• 28 days after last dose  
• 60 days after last dose: follow-up phone call, for a final safety assessment   
The visit windows for the safety assessments are: 28 days +7 days and 60 days +7 days (phone 
call) after the last dose. 
After this protocol-required reporting period, the Investigator does not need to actively monitor 
subjects for SAEs.  However, if the Investigator becomes aware of an SAE/death that may be 
possibly related to study treatment after the protocol-required reporting period, the Investigator 
may report the event to FibroGen as outlined in Section 7. SAEs reported outside of the protocol-
required reporting period will be captured within the safety database only as clinical trial cases 
for the purposes of expedited reporting. 


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6.1.4. 
Early Study Termination Visit 
Subjects who terminate / withdraw from the study early, for any reason, will have an Early Study 
Termination (ET) visit as soon as feasible. Study procedures to be performed during the ET visit 
can be found in the SOA (Appendix 1). At the ET visit, PFTs and questionnaires do not have to 
be repeated, if the last one was performed within 8 weeks of this visit; HRCT does not have to be 
repeated, if the last one was performed within 4 months of this visit. These subjects will have a 
safety follow up visit 28 days after the last dose. A follow-up phone call 60 days after last dose 
will also be completed for a final assessment of safety. 
In addition, these subjects should be contacted by phone for vital status at weeks 24 and 48. 
These subjects will not be eligible for the OLE phase. 
6.1.5. 
Missed Visits 
Scheduled visit dates are determined from the time of the first dose, which is defined as Day 1. 
Protocol-defined visits conducted outside the study visit window (see Section 6.1.2) will be 
recorded as a protocol deviation unless there is an AE/SAE/intercurrent illness or other 
extenuating circumstance (such as during the COVID-19 pandemic), resulting in  “missed” 
visit(s). Refer to Section 5.1.8 for additional details. For missed visits, the subject will be asked 
to resume the planned visit schedule at the next scheduled visit.  
NOTE: In accordance with FDA/ EMA Guidance: During the COVID-19 pandemic, the visit 
modality (e.g.: in-person versus remotely) and scheduling may be adjusted and conducted at the 
discretion of the Investigator, in accordance with the site’s rules and recommendations, and 
using all necessary precautions. If a visit has to be done remotely, it can be conducted with any 
technology available to the site and study subjects, such as via tele-health visits, phone calls, etc. 
Subjects who do not receive all study drug doses, but complete the Week 48 visit, are considered 
study completers, and may be considered for participation in the OLE of pamrevlumab (see also 
Appendix. 6). 
6.1.6. 
Unscheduled Visits 
Unscheduled visits/assessments may be scheduled as needed.  Unscheduled visit data will be 
captured accordingly in the clinical database. 
Unscheduled assessments (PFT/HRCT/PRO/Labs): if these assessments are not done / on a 
scheduled visit, or if a subject misses a visit with these scheduled assessments, they should be 
performed as unscheduled assessments at the next scheduled visit. 
If the subject is unable to perform any assessments at the Week 48 visit, the subject must have an 
unscheduled visit at the nearest possible date to perform any missed Week 48 assessments. 
NOTE: In accordance with FDA/ EMA Guidance: During the COVID-19 pandemic, the visit 
modality (e.g.: in-person versus remotely) and scheduling maybe adjusted and conducted at the 
discretion of the Investigator, in accordance with the site’s rules and recommendations, and 
using all necessary precautions. If a visit has to be done remotely, it can be conducted with any 
technology available to the site and study subjects. 


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6.2. 
Assessments 
Refer to the SOA (Appendix 1) for details regarding the timing and frequency of study 
assessments.  Spirometry, laboratory evaluations and patient reported outcomes assessments 
should be performed prior to infusions.   
6.2.1. 
Vital Signs (including Weight and Height) 
Vital signs to be collected include; heart rate, blood pressure and temperature:   
• Heart rate should be collected as beats/min 
• Systolic and diastolic blood pressure should be collected from subjects in seated 
position (mmHg) 
• Temperature should be taken as oral or tympanic and captured as °F or °C 
Weight is collected during screening, Day 1 and every 12 weeks thereafter.  Height is collected 
during screening only. 
6.2.2. 
Physical Exam 
Full physical exams (PEs) will be performed according to the SOA (Appendix 1). In addition, 
PEs may be performed throughout the study as needed, if clinically indicated. 
6.2.3. 
Electrocardiogram (ECG or EKG) 
12-lead ECGs will be performed in accordance with institutional standards and according to the 
SOA (Appendix 1). In addition, ECGs may be performed throughout the study as needed, if 
clinically indicated. 
6.2.4. 
Laboratory Evaluations 
Details regarding sample collection, preparation and transport can be found in the central lab 
manual.   
6.2.4.1. 
Central Laboratory Evaluations 
The following labs will be evaluated by a central laboratory in accordance with the SOA 
(Appendix 1): 


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Table 2: 
Laboratory Tests 
CBC: 
Chemistry Panel: 
Absolute neutrophil count (ANC) 
Bicarbonate  
Eosinophils 
BUN 
Erythrocyte count (RBC) 
Calcium 
Hematocrit % 
Creatinine 
INR 
Chloride 
PT/PTT 
Magnesium 
Hemoglobin 
Glucose 
WBCs (Leukocyte count) 
   ALP 
Lymphocytes 
ALT 
Mean corpuscular volume  
AST  
Monocytes 
Bilirubin, total  
Neutrophils 
Albumin 
Platelets 
Phosphorous 
Basophils 
   Potassium 
 
   Sodium 
 
   Cholesterol  
 
Total Protein  
 
GGT 
 
Triglycerides  
Pregnancy Test: Urine; Serum hCG at screening and to confirm a positive urine test 
Abbreviations:         ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = 
Gamma-glutamyltransferase; BUN = blood urea nitrogen; CBC = complete blood count; INR = international 
normalized ratio; PT/PTT = prothrombin time/partial thromboplastin time; RBC = red blood cell; 
WBCs = white blood cells; hCG =Human chorionic gonadotropin 
 
Central lab results obtained during the screening period will be used to determine subject 
eligibility for participation in the trial.  Central lab results will be reviewed by the Investigator 
for clinical significance and to determine appropriate reporting of adverse events  
(see Section 7.3).  A Central Laboratory Manual with instructions on specimen collection, 
processing, storing, and shipping to the central laboratory will be provided to all participating 
sites. 
Local laboratory assessments are not required for this study, but the results of any local 
laboratory assessments may be used to assess subject safety. If a local lab abnormality is 
reflective of an AE, report the etiology, if known, as per section 7.3.7.  Local laboratory results 
will not be captured in the clinical database. 


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NOTE: Local laboratory assessments may also be used in case of Central Laboratory supply 
shortages or shipment delays. If local laboratory assessments are used instead of central labs, the 
following points need to be considered: 
• In case of local screening labs, the Investigator needs to review the results with respect to 
Exclusion #10. 
• For on-study laboratory assessments, only laboratory abnormalities that are considered 
clinically significant in the Investigator’s assessment need to be reported as TEAEs, as 
per Protocol Section 7.3.7. In such a case, if possible, the etiology of a lab abnormality 
should be reported as TEAE, not the abnormal lab value. 
• For specialty labs, please collect HAHA samples according to the SOA in Appendix 2 
using local supplies while processing/storing these samples as described in the ICON lab 
manual. Other specialty samples (PK, Biomarkers, Genomic and CTGF) will not be 
required if local labs are being used 
Note: For Czech Republic only, Tuberculosis (TB) screening test to be done using site local 
lab, if this test was not performed within 6 months prior to screening per study exclusion criteria 
23. 
6.2.4.2. 
Pharmacokinetics (PK) and Pharmacodynamics 
Additional samples will be collected to evaluate PK, HAHA, HAHA-NA, CTGF, exploratory 
biomarkers and genomics in accordance with the SOA in Appendix 2. The central laboratory will 
manage the storage of these samples while analysis will be performed at a specialty lab. 
6.2.4.2.1. Pharmacokinetics (Optional) 
An optional PK assessment will be performed in a subset of subjects at select sites. PK 
assessments will continue to be optional except in the case of suspected hypersensitivity/anaphylactic 
reactions (see Section 6.2.4.2.3 for more detail).  Plasma samples will be collected for estimates of 
PK parameters using population PK and exposure-response analysis, if possible, according to the 
SOA in Appendix 2. A specialty laboratory will measure plasma pamrevlumab levels using a 
validated assay.  For the population PK analysis, it is critical to accurately record the dosing time 
and date in addition to the sampling collection time and date. Both pre-dose and post-dose 
samples are required for PK. The pre-dose PK sample should be taken within 2 hours prior to 
dosing, the post-dose PK sample should be between 1-4 hours after the end of dosing. 
6.2.4.2.2.  Human Anti-Human Antibodies (HAHA) 
Plasma samples will be collected for evaluation of human anti-human antibodies (HAHA) , in all 
subjects according to the SOA in Appendix 2. A specialty laboratory will measure HAHA titers 
using a validated assay.   
Samples with positive HAHA results will be tested for neutralizing antibody (HAHA-NA) . The 
prevalence and duration of binding and neutralizing antibodies and the effect of these antibodies 
on the pharmacokinetics, pharmacodynamics markers, efficacy, and safety of pamrevlumab will 
be assessed. 


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6.2.4.2.3. Suspected Hypersensitivity or Anaphylactic Reactions 
Any immunogenic reactions, including drug-related hypersensitivity or anaphylaxis, should have 
PK, HAHA, HAHA-NA, CTGF and tryptase drawn within 24 hours of a suspected reaction from 
pamrevlumab (see Appendix 2 for more detail). This is in addition to timepoints in which PK, 
HAHA, and HAHA-NA and CTGF were drawn pre-infusion and post-infusion. 
This will not be considered optional for the subject unless there is local institutional guideline 
consideration for total blood volume collection on the same day as a standard blood draw timepoint, 
which could preclude the subject from having this collection take place within 24 hours. The 
Tryptase sample should be drawn within 1 to 6 hours of immunogenic reaction, and all other samples 
should be collected within 24 hours of the immunogenic reaction. See Appendix 2 for more detail. 
6.2.4.2.4. Exploratory Biomarkers  
Serum and plasma samples will be collected in all subjects according to the SOA in Appendix 2. 
These samples will be stored and used to explore additional biomarkers of pamrevlumab’s 
effects in the context of the current clinical trial.  
Exploratory biomarkers to be analyzed may include markers of inflammation such as CRP, TNF, 
IL-6, IL-8 and CCL18; markers of fibrosis and collagen synthesis such as TGF-beta, PINP and 
PIIINP, as well as other markers of tissue remodeling and angiogenesis such as angiopoietins, 
VEGF, MMP7 and KL-6. 
NOTE: Biomarker samples will be collected, except in countries where the Regulatory Agencies 
do not allow collection of these markers.  
6.2.4.2.5. DNA for Genomic Analysis (Optional) 
A genome-wide association study was performed in subjects with fibrotic idiopathic interstitial 
pneumonias (N = 1616) and controls (N = 4683) (Fingerlin, 2013) and determined an association 
of disease with TERT and MUC5B on chromosomes 5p15 and 11p15, respectively, the 
chromosome 3q26 region near TERC, and identified 7 novel chromosome loci. The novel loci 
include FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13), and 
chromosomal regions 7q22 and 15q14-15. Their findings indicate that genes involved in host 
defense, cell-cell adhesion, and DNA repair contribute to the risk of fibrotic pulmonary disease. 
In this study, we plan to collect whole blood samples to isolate patient DNA and evaluate the 
relationship between clinical response to pamrevlumab and variants in loci such as those 
described above. 
A whole blood sample will be collected for DNA analysis on Day 1 before dosing for all subjects 
who agree to DNA analysis. This testing is optional, requires specific consent by participating 
subjects and subjects may refuse DNA testing. Only tests for genetic loci associated with ILD, 
fibrosis or CTGF biology will be performed and all samples will be destroyed after testing is 
completed. 
NOTE: DNA samples for genomics analysis will be collected for subjects who consent, except 
in countries where the Regulatory Agencies do not allow collection of these samples. 


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6.2.5. 
High Resolution Computerized Tomography (HRCT) Scans and Spirometry 
The key study procedures that measure efficacy are serial spirometries to assess lung function 
(refer to the PFT Procedure Manual for additional details) and serial HRCT assessments to 
evaluate fibrosis. These measurements will be performed in all patients according to the SOA in 
Appendix 1.  
 
HRCT: 
An Independent Radiology Review Group is assessing all HRCTs for: 
- 
Quantitation of fibrosis, a secondary efficacy measure, and 
- 
Confirmation of HRCT-related eligibility, specifically:  
o Inclusion # 4 
o Exclusion # 2 
Assessment of UIP pattern. For the screening HRCT, the Independent Radiology Review Group 
is providing their assessment to study sites, in accordance with the Independent Radiology 
Review Imaging Charter. It is the responsibility of the Investigator to review this assessment 
prior to randomization, to make sure all HRCT-related eligibility criteria are met. 
For the screening HRCT: if a recent scan, i.e., within 3 months prior to screening, is available, it 
can be utilized as the screening HRCT, provided it is submitted and evaluated by the 
Independent Radiology Imaging Review Group, is adhering to the same imaging acquisition 
parameters detailed in the Imaging Core Manual (ICM), and is either using the same accredited 
scanner, or is performed using the same modality, as the on-study HRCT scans.  
Spirometry: 
Subjects must have an FVCpp value >45% and <95% at screening and Day 1 (prior to 
randomization), in order to be eligible for the study.  
For the screening FVCpp value and GAP score calculation: the quality-controlled, Best-Test 
Review (BTR) assessment provided by the spirometry vendor over-reader, which is provided to 
sites within 48 hours after uploading the test, is to be used for eligibility assessment and GAP 
score calculation.  
For the Day 1 (pre-randomization) FVCpp value: the real-time value obtained from the device is 
to be used for eligibility confirmation, without the need to wait for the BTR assessment.  
BTR assessments of all spirometries are conducted for statistical purposes, and will be provided 
to the site, for quality feedback. 
NOTE: For spirometries deemed “unacceptable” by the spirometry vendor over-reader, the test 
has to be repeated. 
6.2.6. 
Patient Reported Outcomes (PROs) 
Patient reported outcome (PRO) data will be collected in all subjects to evaluate specific patient 
reported symptoms, treatment related symptoms and functional impacts that may be responsive 
to treatment.  All questionnaires will be administered as specified in the SOA (see Appendix 1)  


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in the same order at Week 48 as was done at baseline. On weeks where both questionnaires and 
spirometry are performed, the PFT should be completed prior to administering the PRO. 
6.2.6.1. 
St. Georges Respiratory Questionnaire (SGRQ) 
The St. Georges Respiratory Questionnaire is a disease-specific instrument designed to measure 
impact on overall health, daily life, and perceived well-being in patients with obstructive airways 
disease. 
6.2.6.2. 
University of California, San Diego – Shortness of Breath Questionnaire (UCSD-
SOBQ) 
The UCSD-SOBQ is a self-administered rating of dyspnea associated with activities of daily 
living (ADLs).  The questionnaire is designed to assess severity of shortness of breath during 
specific ADLs and to assess the limitations due to shortness of breath, fear of harm from 
overexertion and fear of shortness of breath. 
6.2.6.3. 
Leicester Cough Questionnaire (LCQ) 
The Leicester Cough Questionnaire is a self-administered instrument designed to monitor 
individual patients cough, assess different aspects of health affected in patients and detect 
changes in health status within an adult chronic cough population (Birring, 2003).   


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7. 
ASSESSMENTS OF SAFETY 
7.1. 
Background 
Adverse event reports from Investigators are the critical building blocks to the development of 
the safety profile of the Study Drug. Subjects will be asked non-leading questions in general 
terms to determine the occurrence of AEs, according to the schedule outlined in Appendix 1. In 
addition, all AEs reported spontaneously during the course of the study will be recorded. The 
Investigator must immediately (within 24 hours of awareness) report to the Sponsor or 
designated safety management vendor all SAEs, regardless of whether the Investigator believes 
they are related to the study drug. 
7.2. 
Definitions 
7.2.1. 
Definition of an Adverse Event (AE) 
An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The 
event does not necessarily have a causal relationship with study treatment. The Investigator is 
responsible for ensuring that any adverse events observed by the Investigator or reported by the 
subject as defined in the study protocol are recorded in the subject’s medical record. The 
definition of adverse events includes worsening of a pre-existing medical condition. Worsening 
indicates that the pre-existing medical condition (e.g., diabetes, migraine headaches and gout) 
has increased in severity, frequency, and/or duration, and/or has an association with a 
significantly worse outcome. A pre-existing condition that has not worsened during the study or 
involves an intervention, such as elective cosmetic surgery, or a medical procedure while on 
study, is not considered an adverse event. 
7.2.2. 
Definition of a Serious Adverse Event (SAE) 
A serious adverse event is any adverse event or suspected adverse reaction that results in any of 
the following outcomes: 
• Death, 
• A life-threatening AEs (i.e., if in the view of the Investigator or Sponsor, the subject 
was at immediate risk of death at the time of the event). Life-threatening does not 
refer to an event which hypothetically might have caused death if it were more 
severe, 
• Inpatient hospitalization or prolongation of existing hospitalization, 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, 
• A congenital anomaly or birth defect, or 
• Is considered a medically important event not meeting the above criteria, but which 
may jeopardize a subject or may require medical or surgical intervention to prevent 
one of the other criteria listed in this definition. Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or 


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at home, and blood dyscrasias or convulsions that do not result in inpatient 
hospitalization. 
Please note that death is an outcome, not an event; the primary cause of death would be the 
adverse event. 
Surgical procedures, per se, are not SAEs. The condition requiring the surgical procedure, 
however, may be a SAE. 
Scheduled or pre-planned hospitalization or prolongation of a hospitalization due to standard of 
care assessments and procedures (including elective procedures) do not warrant reporting as 
adverse events unless resulting observations are deemed by the Investigator to meet the 
definition of an adverse event. 
7.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events 
7.3.1. 
Adverse Event Reporting Period 
The safety reporting period begins after the subject has signed the informed consent and ends 60 
days after the last dose of study drug.  It is only required that SAEs be reported prior to first 
dose, while all AEs (serious and non-serious) be reported thereafter.  The Investigator should 
notify FibroGen of any death or other SAEs occurring after a subject has discontinued or 
terminated study participation that may reasonably be related to this study (Section 7.3.5). 
Pregnancy reporting requirements are outlined in Section 7.3.6. 
Adverse events will be followed until resolved, stable, or until the subject’s last study visit or 
subject is lost to follow-up. 
7.3.2. 
Adverse Event Eliciting/Reporting 
During the AE reporting period, study site personnel will actively seek information from each 
subject at each visit to collect any AEs occurring since the previous visit. All AEs will be 
collected in response to a general question about the subject’s well-being and any possible 
changes from the BL or previous visit. There will be no directed questioning for any specific AE. 
This does not deter the site from collecting and recording any AEs reported by the subject to site 
personnel at any other time. 
Whenever possible, diagnoses should be recorded when signs and symptoms are due to a 
common etiology, as determined by qualified medical study staff. The Investigator is responsible 
for reviewing laboratory test results and determining whether an abnormal value in an individual 
study subject represents a clinically significant change from the subject’s baseline values. In 
general, abnormal laboratory findings without clinical significance (based on the Investigator's 
judgment) are not to be recorded as adverse events. However, laboratory value changes that 
require treatment or adjustment in current therapy are considered adverse events. Where 
applicable, clinical sequelae (not the laboratory abnormality) are to be recorded as the adverse 
event. The Investigator is expected to follow reported adverse events until stabilization or 
reversibility. 


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The following attributes must be assigned to each AE: 
• Description (Investigator’s verbatim term describing the event) 
• Dates of onset and resolution 
• Severity 
 
• Relationship to study drug 
• Outcome 
• Action taken regarding study drug 
• Other treatment required 
• Determination of “seriousness” 
7.3.3. 
Assessing Adverse Event Severity 
AEs, including abnormal clinical laboratory values, should be graded using the most current 
National Cancer Institute (NCI) Common Terminology Criteria for AE (CTCAE) guidelines. For 
terms not specified as part of NCI CTCAE, the following guidelines should be used to determine 
grade: 
All AEs will be assessed for severity using the following criteria: 
• Grade 1, Mild: Asymptomatic or mild symptoms which the subject finds easily 
tolerated. The event is of little concern to the subject and/or of little-or-no clinical 
significance; intervention not indicated. 
• Grade 2, Moderate: The subject has enough discomfort to cause interference with or 
change in some of their age-appropriate instrumental activities of daily living (e.g., 
preparing meals, shopping for groceries or clothes, using the telephone, managing 
money); local or noninvasive intervention indicated. 
• Grade 3, Severe: The subject is incapacitated and unable to work or participate in 
many or all usual activities. The event is of definite concern to the subject and/or 
poses substantial risk to the subject’s health or well-being; likely to require medical 
intervention and/or close follow-up, including but not limited to hospitalization or 
prolongation of hospitalization. 
• Grade 4, Life-threatening:  The subject was at immediate risk of death from the 
event as it occurred. 
• Grade 5, Death: Fatal AE. 
7.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug 
Most of the information about the safety of a drug prior to marketing comes from clinical trials; 
therefore, AE reports from Investigators are critically important. The assessment of whether an 
AE is causally related to the study drug(s) using an evidence-based approach is critical in order 
to appropriately describe the safety profile of the study drug(s). Default reporting of individual 
events as possibly related is uninformative and does not meaningfully contribute to the 
development of the study drug’s safety profile. 


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The Investigator must provide an evidence-based assessment of the relationship of the AE to 
study drug in accordance with the guidance below. Absence of an alternative cause would not 
normally be considered sufficient evidence to assess an event as related to study drug. 
• Related: 
− Any event for which there is sufficient evidence to suggest that the study drug 
may have caused the event. For example, an unanticipated medical condition 
occurs which resolves with study drug interruption and re-occurs with re-
administration of study drug; another example is a typical drug-related medical 
condition such as a rash that occurred shortly after first dose of study drug. 
• Not Related: 
− The event represents a pre-existing underlying disease that has not worsened on 
study 
− The event has the same characteristics of a known side-effect associated with a 
co-medication 
− The event is an anticipated medical condition of anticipated severity for the study 
population 
− The most plausible explanation for the event is a factor that is independent of 
exposure to study drug 
7.3.5. 
Reporting Serious Adverse Events (SAEs) 
The Investigator is responsible for ensuring that all SAEs observed by the Investigator or 
reported by the subject that occur after signing of the informed consent through 60 days after the 
last dose of pamrevlumab are recorded in the subject’s medical record and are submitted to 
FibroGen. All SAEs must be submitted to FibroGen within 24 hours following the Investigator’s 
knowledge of the event via the SAE report form. Additionally, pamrevlumab related SAEs 
(including deaths) that occur after the Safety Follow-up visits will be reported. 
If a subject is permanently withdrawn from protocol required therapies because of a serious 
adverse event, this information must be submitted to FibroGen. FibroGen will report serious 
adverse events and/or suspected unexpected serious adverse reactions as required to regulatory 
authorities, Investigators/institutions, and central IRBs/IECs in compliance with all reporting 
requirements according to local regulations and Good Clinical Practice (GCP). 
There is no requirement to monitor study subjects for serious adverse events following the 
protocol-required reporting period or after end of study. However, these serious adverse events 
can be reported to FibroGen if the Investigator becomes aware of them. If serious adverse events 
are reported, the Investigator is to report them to FibroGen within 24 hours following the 
Investigator’s knowledge of the event. Serious adverse events reported outside of the protocol-
required reporting period will be captured within the safety database as clinical trial cases for the 
purposes of expedited reporting; these cases will not be included in the clinical study report. 
To report an SAE, the Investigator must complete an SAE Report Form and fax or email the 
completed form to the Sponsor or its designated safety management vendor. 


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Full details of the SAE should also be recorded on the medical records and in the CRF. The 
following minimum information is required: 
• Subject number, sex and age 
• The date of report 
• A description of the SAE (event, seriousness of the event) 
• Causal relationship to the study drug 
Follow-up information for the event should be sent promptly. 
For each SAE observed, the Investigator should obtain all of the information available about the 
event, including (but not limited to): hospital discharge diagnoses, hospital discharge note, death 
certificate, appropriate laboratory findings (including autopsies and biopsy results), and clinical 
examinations (including radiological examinations and clinical consultations). 
7.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review Board / 
Independent Ethics Committee 
The Investigator is responsible for notifying his/her Institutional Review Board (IRB) or Ethics 
Committee (EC) of SAEs in accordance with local regulations. The Sponsor, or its designated 
safety vendor, will provide a copy of expedited safety reports to the Investigator that it intends to 
submit to global regulatory authorities. 
7.3.5.2. 
Deaths 
The Investigator will report the fatal event to the Sponsor’s medical monitor. The Investigator 
must provide a causal assessment of the relationship of the event to the study drug according to 
the guidance in Section 7.3.4. 
If the death occurred within the AE collection and reporting period (signed ICF to 60 days after 
last dose) and meets the reporting criteria, the Investigator must submit the SAE Report Form in 
the same manner as described above in Section 7.3.5. If the Investigator becomes aware of a 
death occurring after the AE reporting period and considers it related to pamrevlumab, it will be 
reported as an SAE.  
7.3.6. 
Pregnancies: Reporting and Follow-up of Subjects and Female Partners of 
Subjects  
The outcome of all pregnancies for female subjects or female partners of male subjects should be 
followed up and documented as described. If a female subject or a female partner of a male 
subject becomes pregnant while the subject is receiving study treatment or within 12 weeks after 
the last dose of study treatment, a Pregnancy Report Form must be completed and submitted to 
the Sponsor or designated safety management vendor within 24 hours of the Investigator 
becoming aware of the pregnancy. The Investigator must follow-up to completion of the 
pregnancy to ascertain its outcome (e.g., spontaneous miscarriage, elective termination, ectopic 
pregnancy, normal birth or congenital abnormality) and whether any AEs occur during the 
pregnancy or birth. The outcome of the pregnancy must be reported by the Investigator on a 
Pregnancy Outcome Report Form, which should be sent to the Sponsor and/or its designated 
safety vendor within 24 hours of the Investigator becoming aware of the outcome.  


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Pregnancy itself is not an AE unless there is a suspicion that the investigational product under 
study may have interfered with the effectiveness of a contraceptive medication. Pregnancies are 
followed up to outcome even if the subject was discontinued from the study. Congenital 
abnormalities/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs.  
If a lactation case occurs while the female subject is taking protocol-required therapies, or within 
60 days after the last dose of study treatment, report the lactation case to FibroGen. In addition to 
reporting a lactation case during the study, investigators should monitor for lactation cases that 
occur after the last dose of protocol-required therapies through 60 days after the last dose of 
pamrevlumab.  Any lactation case should be reported to FibroGen’s Safety within 24 hours of 
the investigator’s knowledge of event.  
7.3.7. 
Laboratory or other Test Abnormalities/ Findings 
A laboratory or other test abnormality (e.g., spirometry, HRCT) in the absence of any signs or 
symptoms is not necessarily an AE. The Investigator must review and assess all test results 
provided by the central laboratory or other vendors throughout the study in a timely manner, and 
determine whether any abnormal values/test results are clinically significant (CS) or not 
clinically significant (NCS), and whether there are associated signs and symptoms. Such 
abnormalities should be considered CS if they are associated with new signs or symptoms, if 
they occur after taking study medication, reflect a meaningful change from the screening 
value(s), or require active management (e.g., requiring treatment, additional testing, study 
treatment dose modification, discontinuation, more frequent follow-up assessments, etc.).  
Clinically significant laboratory abnormalities will be reported as AEs. If the abnormal 
laboratory finding is accompanied by signs or symptoms, report the signs and symptoms as the 
AE in lieu of the abnormal laboratory value. If a diagnosis is available, report the diagnosis. 
7.3.8. 
Hypersensitivity/Anaphylactic Reactions: 
Hypersensitivity and anaphylactic reactions will be monitored throughout the study, using the 
criteria below as defined per Sampson et al. 2006 (Sampson, 2006). 
Anaphylaxis is highly likely when the following criteria is fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-
uvula). 
And at least one of the following criteria: 
a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours):  
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen 
lips-tongue-uvula)  


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b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia)  
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. Systolic BP of less than 90 mm Hg or greater than 30% decrease from that person's 
baseline 
7.3.9. 
Safety Monitoring  
Safety will be assessed throughout the study. A medically complete baseline profile of each 
subject will be established through medical history, a complete physical examination including 
vital signs, laboratory tests, PFTs, and a 12-lead ECG. During the course of the study, vital signs, 
laboratory tests, and PFTs will be performed at frequent intervals as described in Appendix 1 and 
Appendix 2. Any medically significant changes from baseline will be monitored throughout the 
study and appropriate interventions will be taken accordingly. Safety and tolerability will be 
monitored closely by FibroGen. 
7.3.9.1. 
Special Reporting Situations 
Special Reporting Situations on FibroGen investigational product pamrevlumab (or placebo) that 
require safety evaluation include: 
• Overdose (any dose greater than 4.1g) 
• Suspected abuse/misuse 
• Inadvertent or accidental exposure 
• Medication error (e.g. incorrect dose administered) 
• Drug-drug interactions 
Report special situations to FibroGen’s Safety within 24 hours of the investigator’s knowledge of 
the event. See Study Reference Manual for detailed reporting instructions. 
7.3.9.2. 
Data Monitoring Committee (DMC) 
A Data Monitoring Committee (DMC) will be utilized and will be composed of external experts. 
Composition and responsibilities of the DMC will be defined in a separate DMC charter. The 
DMC responsibilities will include review of the safety data.  
  


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8. 
STATISTICS 
8.1. 
Sample Size Determination 
This study will enroll approximately 340 subjects with a 1:1 randomization ratio to pamrevlumab 
or placebo, respectively.  
A sample size of 340 subjects will have at least 90% power, based on a two-sided alpha level of 
0.05 for a two-sample t-test, to detect a treatment difference of 120 mL in the primary efficacy 
endpoint, change from baseline in FVC (L), assuming a common standard deviation of 300 mL. 
This sample size allows for a dropout rate of  approximately 20%.   
The rationale for these sample size assumptions are as follows. In the phase 2 study FGCL-3019-
067, a treatment difference of 178 mL was observed in change from baseline in FVC to Week 
48. For this study, a conservative treatment difference of 120 mL is assumed. The standard 
deviation is estimated based on published results from other IPF studies.  
8.2. 
Analysis Populations 
8.2.1. 
Intent to Treat (ITT) Population 
The ITT population is defined as all randomized subjects. Subjects will be analyzed according to 
the treatment as randomized. 
8.2.2. 
Safety Population 
The safety population is defined as all subjects who have received the study medication.   
Subjects will be analyzed according to the treatment as received. 
8.3. 
Statistical Analysis 
8.3.1. 
General Considerations 
The primary efficacy endpoint will be tested at the significance level of 0.05 (2-sided).  Upon 
observing a significant treatment difference in the primary endpoint, the secondary endpoints 
will be tested sequentially in a fixed sequence according to the order listed in section 3.2.2, 
taking into consideration the adjustment for the family-wise error-rate of 0.05 (2-sided). The 
testing will continue with the significance level of 0.05 (2-sided) in sequential fashion until the 
test fails to show statistical significance for a secondary endpoint. 
Baseline characteristics, safety, efficacy, and biomarker data will be summarized by treatment 
arm, based on available data in the ITT and/or Safety Population.  
All study parameters will be presented in the data listings and summarized descriptively by visit. 
Descriptive statistics for continuous variables include: n, mean, standard deviation or standard 
error, median, minimum, and maximum. Categorical variables will be presented by frequency 
count of subjects and percentage. Two-sided 95% confidence intervals will be provided. 
Efficacy and safety analyses for treatment arm (pamrevlumab vs placebo) comparisons will only 
be based on data observed during the main study that is double-blind and placebo-controlled.  
Data from the OLE period will be summarized descriptively. 


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8.3.2. 
Subject Enrollment and Disposition 
The number (%) of subjects who completed or discontinued the study, and reasons for early 
discontinuation, will be summarized by treatment for subjects in the ITT population. 
8.3.3. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics will be summarized for subjects in the ITT 
population. 
8.3.4. 
Efficacy Analyses 
The analysis population is all randomized subjects to reflect the intent-to-treat (ITT) principle for 
all analyses.  
8.3.4.1. 
Primary Endpoint Analysis 
The primary estimand is intended to provide a population level estimate of the treatment effects 
of the pamrevlumab on a continuous endpoint, regardless of participants compliance with the IP 
dosing. Under an estimand framework, the analysis of primary endpoint includes the following 
components: 
Population: Male and female patients aged 40 to 85 years, inclusive at screening initiation with 
IPF diagnosis made within 7 years prior to screening under American Thoracic Society/European 
Respiratory Society (ATS/ERS) criteria (Raghu 2018), and not currently receiving treatment 
with the 2 approved antifibrotic standard of care medications. All subjects in ITT population will 
be included. 
Endpoint: Change from baseline in FVC (L) assessment at Week 48. 
Treatment of interest: The randomization study treatment (pamrevlumab or placebo). 
Handling of intercurrent events: The treatment policy strategy will be adopted for primary 
analysis. Details on handling missing values will be defined in a Statistical Analysis Plan (SAP). 
Population-level summary for the endpoint: Absolute LSMeans difference between 
pamrevlumab and placebo in change from baseline to Week 48 in FVC (L) estimated from a 
random coefficient model (RCM), the primary analysis approach. RCM model includes 
treatment, visit (as a continuous variable), visit-by-treatment interaction, randomization 
stratification factor, baseline FVC volume, age, sex, height as fixed effects, and the intercept and 
linear slope of visit as random effects. Details of RCM model will be defined in the SAP. 
Additional sensitivity and supplemental analyses on primary endpoint will be defined in the 
SAP. The following analysis will be performed including, but not limited to: 
1. With alternative model using quadratic assumption of FVC decline 
2. Alternative assumptions for missing data (imputation method): 
a. Missing not at random: Pattern mixture model (e.g., control-based imputation) 
b. Missing not at random: Tipping point analysis (e.g., delta-adjusting pattern 
imputation)  


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8.3.4.2. 
Secondary Endpoint Analyses 
The secondary estimands are intended to provide a population level estimate of the treatment 
effect of the pamrevlumab on time-to-event endpoints and continuous endpoint, regardless of 
participants compliance with the IP dosing. Under estimand framework, the analysis of 
secondary endpoint includes the following components: 
Population: Same as primary estimand. 
Endpoints: 
• Time to disease progression, defined as absolute FVCpp decline of ≥10% or death, 
whichever occurs first 
• Change in Quantitative Lung Fibrosis (QLF) volume from baseline at Week 48 
• Time to any component of clinical composite endpoint, whichever occurs first: acute 
IPF exacerbation, respiratory hospitalization, or death 
• Time to first acute IPF exacerbation during study 
• Time to all-cause mortality during study 
• Time to first respiratory hospitalizations during study 
Treatment of interest: Same as primary estimand.  
Handling of intercurrent events: 
For time-to-event endpoints, treatment policy strategy will be adopted. For death, composite 
strategy will be used if death is a component of the endpoint. Censoring rules will be defined in 
the SAP. 
For QLF, the same strategy as primary estimand will be applied.  
Population-level summary for the endpoint:  
For time-to-event endpoints: The hazard ratio and corresponding 95% CI from Cox proportional 
hazard model will be presented. P-value from stratified Log-rank test will also be reported. 
Details will be defined in the SAP. 
For QLF endpoint: treatment difference of Least-square mean (LSMean) and SE at week 48 
between pamrevlumab and placebo and the corresponding 95% CI derived from a Mixed Model 
for Repeated Measure (MMRM) will be presented. The MMRM model includes treatment, visit, 
treatment-visit interaction, randomization stratification factor, and baseline endpoint value as 
fixed effects. 
8.3.4.3. 
Exploratory Analyses 
Patient reported outcomes (PROs) including SGRQ, UCSD-SOBQ and LCQ will be analyzed 
using same MMRM model as QLF. Absolute and relative FVCpp will be analyzed with similar 
RCM model as FVC excluding the covariates adjusted for FVCpp. Time to composite of 
respiratory hospitalization, absolute FVCpp decline ≥10%, or death will be analyzed similar to 
other secondary time-to-event endpoints. Biomarkers will be summarized.  


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8.3.5. 
Pharmacokinetic Analyses 
A plan for population PK analysis will be provided in the population PK SAP. 
8.3.6. 
Safety Analyses 
Safety data will be summarized based on the Safety population. TEAEs and TESAEs will be 
summarized by treatment arm.  
Clinically significant changes from baseline in vital signs and laboratory tests will be identified 
and summarized by treatment arm. Additionally, hypersensitivity/anaphylactic reactions will be 
monitored and immunogenicity reactions, including neutralizing HAHA formation, will be 
assessed by the treatment arm. 
8.4. 
Interim Analysis 
No interim analysis is planned for this study. 
8.5. 
Statistical Analysis Plan 
The Statistical Analysis Plan (SAP) will include detailed analysis methods, statistical models, 
definitions, missing data handling as well as other data handling rules. It will document detailed 
analyses of the primary, secondary, and additional exploratory endpoints that are not otherwise 
specified in the protocol.  The SAP will be finalized prior to database lock and treatment 
unblinding. 
 


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9. 
QUALITY CONTROL AND QUALITY ASSURANCE 
9.1. 
Data Quality Assurance 
Quality assurance and quality control systems will be implemented and maintained with 
Standard Operating Procedures by FibroGen and its designee(s), as appropriate, to ensure that 
this clinical study is conducted and data are generated, documented (recorded) and reported in 
compliance with the protocol, ICH E6 (GCP), and other applicable regulations. 
This study will be monitored by FibroGen or designee in accordance with GCP, and may be 
audited or reviewed by an independent Quality Assurance department, IRB/IEC, and/or 
regulatory authorities.  This implies that monitors and auditors/inspectors will have the right to 
inspect the study sites at any time during and/or after completion of the study and will have 
direct access to data/source documents, including the subject's file.  By participating in this 
study, Investigators agree to this requirement. 
The purpose of trial monitoring is to verify the following: 
• The rights and well-being of human subjects are protected. 
• The reported data are accurate, complete, and verifiable from source documents. 
• All data are collected, tracked, and submitted by the site to FibroGen or designee, 
including unscheduled and missed assessments 
• The reported data are reconciled across all data sources (e.g., laboratory, safety, IRT, 
clinical databases). 
• The conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s). 
Measures will be undertaken to protect the confidentiality of records that could identify subjects, 
respecting the privacy and confidentiality rules in accordance with applicable regulatory 
requirements. 
9.2. 
Audit and Inspection 
Authorized representatives of the Sponsor, a regulatory authority, and/or an IRB/IEC may visit 
the Investigator site to perform audits or inspections, including source data verification and 
source documentation review. The Investigator will allow the Sponsor auditor (or designee), 
regulatory authority or ethics committee representative to inspect the drug storage area, study 
drug stocks, drug accountability records, subject charts (e.g. medical records) and study source 
documents, and other records relative to study conduct. 
The purpose of an audit or inspection is to systematically and independently examine all study-
related activities and documents to determine whether these activities were conducted, and data 
were recorded, analyzed, and accurately reported according to the protocol, ICH GCP guidelines, 
and any applicable regulatory requirements. 
The Investigator must contact the Sponsor, or its third party representative (CRO), immediately 
if notified by a regulatory authority of an inspection pertaining to this study. 


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10. 
ETHICS 
10.1. 
Ethical Considerations 
The study will be conducted in accordance with applicable regulatory requirements, the 
International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice 
(GCP), the Declaration of Helsinki, any other applicable regulatory requirements, and 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) requirements. 
10.2. 
Communication with the Institutional Review Board or Independent 
Ethics Committee 
This protocol, the Informed Consent Form, the IB, and any information to be given to the subject 
must be submitted to a properly constituted IRB/IEC by the Investigator for review and approved 
by the IRB/IEC before the study is initiated and before any investigational product is shipped to 
the investigator. In addition, any subject recruitment materials must be approved by the IRB/IEC 
before the material is used for subject recruitment. 
The Investigator is responsible for obtaining reapproval by the IRB/IEC annually or as required 
by the policies and procedures established by the IRB/IEC. Copies of the investigator’s annual 
report and other required reports submitted to the IRB/IEC and copies of the IRB/IEC 
continuance of approval must be furnished to FibroGen or designee. A copy of the signed FDA 
Form 1572 or other qualified Investigator statement (as required) must also accompany the 
above approval letter provided to FibroGen. 
Investigators are also responsible for promptly informing the IRB/IEC of any protocol changes 
or amendments, changes to the IB, and other safety-related communications from FibroGen or its 
designee. Written documentation of IRB/IEC approval must be received before the amendment 
is implemented. 
Investigators must maintain a list of appropriate qualified persons to whom the Investigator has 
delegated significant trial-related duties and update the list as staff and their delegated 
responsibilities change.    
10.3. 
Subject Information and Consent 
Prior to participation in any study-specific procedures, the subject must sign an IRB/IEC-
approved written Informed Consent Form (ICF) in his/her native language.  The approved 
written informed consent must adhere to all applicable laws in regards to the safety and 
confidentiality of the subjects.  To obtain and document informed consent, the Investigator 
should comply with applicable regulations, and adhere to ICH GCP standards and the ethical 
principles in the Declaration of Helsinki (2013, 64th, Fortaleza, Brazil). 
The language in the written information about the study should be as non-technical as practical 
and should be understandable to the subject.  Before informed consent is obtained, the 
Investigator should provide the subject ample time and opportunity to inquire about the study 
and to decide whether or not to participate. 
All questions about the study should be answered to the satisfaction of the subject.  The written 
ICF should be signed and personally dated by the subject and the person who conducted the 


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informed consent discussion, with any additional signatures obtained as required by applicable 
local regulations and IRB/IEC requirements.  Each subject will be informed that participation is 
voluntary and that he/she can withdraw from the study at any time.  All subjects will receive a 
copy of the signed and dated ICF. 
If there are any changes to the IRB/IEC approved ICF during the subjects’ participation in the 
study, the revised ICF must receive the IRB/IEC’s written approval before use and subjects must 
be re-consented to the revised version of the ICF, if/as required by the IRB/IEC. 
Each subject must provide his or her consent for the use and disclosure of personal health 
information in accordance with applicable regulatory requirements. 
10.4. 
Subject Confidentiality 
The confidentiality of records that could identify subjects should be protected, respecting the 
privacy and confidentiality rules in accordance with applicable regulatory requirements.  
Subject medical information obtained as part of this study is confidential and may only be 
disclosed to third parties as permitted by the Informed Consent and HIPAA Authorization Form 
or separate authorization to use and disclose personal health information signed by the subject, or 
unless permitted or required by law.  


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11. 
DATA HANDLING AND RECORD KEEPING 
11.1. 
Source Documents 
Source documents are original documents, data, and records necessary for the reconstruction and 
evaluation of the clinical study. The Investigator or designee will prepare and maintain adequate 
and accurate source documents. These documents are designed to record all observations and 
other pertinent data for each subject enrolled in this clinical study. Source documents must be 
adequate to reconstruct all data transcribed onto the Case Report Forms (CRFs) and resolved 
queries. 
11.2. 
Direct Access to Source Documents 
The Investigator must provide direct access to source data and source documents for trial-related 
monitoring, audits, IRB/IEC review, and regulatory authority inspection.  Direct access includes 
examining, analyzing, verifying, and reproducing any records and reports that are important to 
the evaluation of the study.  The Investigator is obligated to inform and obtain the consent of the 
subject to permit such individuals to have access to his/her study-related records, including 
personal information and medical records. 
11.3. 
Data Collection, Handling, and Verification 
All required data will either be entered onto CRFs by authorized site personnel or will be 
provided as a data transfer from authorized service providers (such as laboratory results from a 
central laboratory). Data will be entered or uploaded into a validated, clinical database compliant 
with 21 CFR Part 11 regulations.  
All subject data will be reviewed by Sponsor and/or designee. Data that appear inconsistent, 
incomplete or inaccurate will be queried for site clarification. 
Medical history, adverse events and medications will be coded using industry standard 
dictionaries (e.g., MedDRA and World Health Organization Drug [WHODrug]) Dictionary. 
The Investigator is responsible for reviewing, verifying, and approving all subject data (i.e. CRFs 
and queries) throughout the duration of the study and prior to study completion, ensuring that all 
data are verifiable with source documents. 
11.4. 
Protocol Deviations 
Unless there is a safety concern, there should be no deviations or violations of the study protocol.  
In the event of a safety concern, the Investigator or designee must document and explain the 
reason for any deviation from the approved protocol.  The Investigator may implement a 
deviation from, or a change to, the protocol to eliminate an immediate hazard to study 
participants without prior IRB/IEC approval.  Immediately after the implemented deviation or 
change, the Investigator must submit a report explaining the reasons for the protocol violation or 
deviation to the IRB/IEC, FibroGen, and to the regulatory authorities, if required. 


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11.5. 
Retention of Data 
A FibroGen representative will inform the Investigator in writing when it is acceptable to dispose 
of any study records.  To enable evaluation and/or audits from regulatory authorities or FibroGen 
or designee, the Investigator agrees to keep records, including the identity of all participating 
subjects (eg, subject identification code list and all source documents), all original signed ICFs, 
copies of all CRFs, original laboratory reports, detailed records of drug disposition and all 
essential documents for the conduct of a clinical study.  To comply with international 
regulations, the records should be retained by the Investigator for 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 until at least 2 years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  
However, the Investigator may need to retain these documents for a longer period if required by 
applicable law, regulatory requirements or by an agreement with FibroGen whichever is longer. 
11.6. 
Financial Disclosure 
The Investigator’s disclosable financial interests must be obtained prior to initiation of the study 
site, at completion of the study at the investigational site, and 1 year following study completion.  
The Investigator should promptly update this information if any relevant changes occur during 
the above described period.  
Disclosable financial interests will be recorded on the Investigator Financial Disclosure Form.  
Any Investigator(s) added as investigational staff to the form FDA 1572 or other qualified 
investigator statement must complete the Investigator Financial Disclosure Form at the 
beginning of his/her participation in the study.  The Investigator Financial Disclosure Form for 
any Investigator(s) leaving the clinical site prior to study completion will be obtained prior to 
study completion. 


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12. 
PUBLICATION POLICY 
The data and results of the study will be owned solely by FibroGen and shall be confidential 
information of FibroGen, subject to the Investigator's publication rights, described below and if 
any outlined in the Clinical Trial Agreement.  It is understood by the Investigator that FibroGen 
may use the information developed in this clinical study in connection with the development of 
its compounds and therefore, may disclose it as required to other clinical investigators, the 
Licensing Authority or to regulatory agencies of other governments.  To allow for the use of the 
information derived from this clinical study, the Investigator understands that he/she has an 
obligation to provide and disclose test results and all data developed during this study to 
FibroGen. 
Any publication or presentation of the results of this clinical study by the Investigator may only 
be made in strict compliance with the provisions of the Clinical Trial Agreement.  Any 
publication relating to the study shall be made in collaboration with FibroGen. The Investigator 
should understand that it is not FibroGen’s intention to prevent publication of the data generated 
in the clinical study.  However, FibroGen reserves the right to control the form and timing of 
such publication for commercial reasons.  The Study Center and Investigator shall adhere to the 
publication language as outlined in both Clinical Trial Agreement and the protocol to the extent 
that if there is any conflict or ambiguity between Clinical Trial Agreement and the protocol, the 
publication terms in the Clinical Trial Agreement shall prevail. 


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Tsakiri KD, Cronkhite JT, Kuan PJ, et al. (2007) Adult-onset pulmonary fibrosis caused by 
mutations in telomerase. Proc Natl Acad Sci U S A 104: (18):7552-7557 
Visscher DW, Myers JL (2006) Histologic spectrum of idiopathic interstitial pneumonias. Proc 
Am Thorac Soc 3: (4):322-329 
Waghray M, Cui Z, Horowitz JC, et al. (2005) Hydrogen peroxide is a diffusible paracrine signal 
for the induction of epithelial cell death by activated myofibroblasts. The FASEB Journal 19: 
(7):854-856 
Walter N, Collard HR, King TE, Jr. (2006) Current perspectives on the treatment of idiopathic 
pulmonary fibrosis. Proc Am Thorac Soc 3: (4):330-338 
Wang Q, Usinger W, Nichols B, et al. (2011) Cooperative interaction of CTGF and TGF-beta in 
animal models of fibrotic disease. Fibrogenesis Tissue Repair 4: (1):4 
Wells AU (2019) Pamrevlumab in idiopathic pulmonary fibrosis. Lancet Respir. Med. 
https://doi.org/10.1016/S2213-2600 (19)30339-X 
Willis BC, DuBois RM, Borok Z (2006) Epithelial origin of myofibroblasts during fibrosis in the 
lung. Proc Am Thorac Soc 3: (4):377-382 
Wilson MS, Wynn TA (2009) Pulmonary fibrosis: pathogenesis, etiology and regulation. 
Mucosal Immunol 2: (2):103-121 
Wuyts, W. A., Ryan, S., and Egan, JJ (2009) Pulmonary Fibrosis. Lung Transplantation. 
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Ziesche R, Hofbauer E, Wittmann K, Petkov V, Block LH (1999) A preliminary study of long-
term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic 
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14. 
APPENDICES 


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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
 
Screening 
Period (Up 
to 6 
Weeks)a 
Dosing Perioda, b,c 
(48 Weeks) 
 
Safety Follow-Up 
Period 
Study Week 
 
Day 1 
(First dose) 
3 
6 
9 
12 
15 
18 
21 
24 
27 
30 
33 
36 
39 
42 
45 
48/ 
Last 
dose/ETt 
28 
days 
after 
last 
doser 
60 days 
after last 
dose phone 
callr 
Assessment 
 
Pre-
dose 
Post-
dose 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sign and date ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xs 
 
 
Eligibility Assessment 
(Inclusion/Exclusion) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Labs  
X 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
TB testu (For Czech 
Republic Only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical Examd,e  
Xd 
Xd 
 
 
 
 
Xd 
 
 
 
Xd 
 
 
 
Xd 
 
 
 
Xd 
 
 
ECGf 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infusionsg,h,v 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xt 
 
 
Adverse Events i 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
j 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xj 
Procedures and Nondrug 
Therapiesj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xj 


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Screening 
Period (Up 
to 6 
Weeks)a 
Dosing Perioda, b,c 
(48 Weeks) 
 
Safety Follow-Up 
Period 
Study Week 
 
Day 1 
(First dose) 
3 
6 
9 
12 
15 
18 
21 
24 
27 
30 
33 
36 
39 
42 
45 
48/ 
Last 
dose/ETt 
28 
days 
after 
last 
doser 
60 days 
after last 
dose phone 
callr 
Assessment 
 
Pre-
dose 
Post-
dose 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DLCO 
Xk 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PFTs 
X 
Xl 
 
 
Xl 
 
Xl 
 
Xl 
 
Xl 
 
 
 
Xl 
 
 
 
Xl,t 
 
 
HRCT of Chest 
Xm 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Xt 
 
 
SGRQn 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
Xt 
 
 
UCSD-SOBQn 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
Xt 
 
 
Leicester Cough Qn 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
Xt 
 
 
Pregnancy Test 
(WOCBP)o 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xp 
X 
Xo 
Assess vital status (in 
subject who terminate 
/withdraw from study 
early)  
 
 
 
 
 
 
 
 
 
 
Xq 
 
 
 
 
 
 
 
Xq 
 
 
Abbreviations: AE = adverse event; CBC = complete blood count; DLCO = diffusing capacity of the lungs for carbon monoxide; ECG = electrocardiogram; ET= Early 
Termination; hCG = human chorionic gonadotropin; HRCT = high resolution computed tomography; ICF = Informed Consent Form; PFTs = Pulmonary Function Test; SGRQ = 
Saint George’s Respiratory Questionnaire; UCSD-SOBQ = University of California San Diego – Shortness of Breath Questionnaire: WOCBP = Woman of child bearing potential; 
TB = Tuberculosis 
 
a.) Plans to re-screen a subject must be discussed with, and approved by, the Medical Monitor prior to re-screening. 
b.) Visit window of ±7 days, Week 3 through Week 48. The visit window of ±7 days also applies to assessments that cannot be performed on the same day; these assessments are 
considered part of that specific visit, and are to be labelled as such. Missed visits are not to be made up between scheduled visits, subject is to return for the next scheduled visit. 
c.) Unscheduled visit assessments (procedures) performed as necessary. During the COVID-19 pandemic, the visit modality (e.g.: in-person versus remotely) and scheduling 
maybe adjusted and conducted at the discretion of the Investigator, in accordance with the site’s rules and recommendations, and using all necessary precautions. If a visit has to be 
done remotely it can be conducted with any technology available to the site and study subjects.    
d.) Height is measured only at screening. Weight is measured at screening, Day 1(to calculate the starting dose), and every 12 weeks thereafter to determine the need for dose 
adjustment. 
e.) Additional PE’s may be performed as needed, if clinically indicated.    


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f.) Additional ECGs may be performed as needed, if clinically indicated. 
g.) Study drug infusions are Q3W starting on Day 1. NOTE: infusions must be at least 10 days apart; missed doses are not to be made up between scheduled visits, subject is to 
return for the next scheduled visit/dose. Vital signs (blood pressure, pulse, and temperature) must be recorded prior to, and after each infusion, according to Section 5.1.6. 
h.) If during a home infusion a new safety concern arises, the subject has to attend an on-site visit for an Investigator assessment as soon as feasible. 
i.) See Section 7 for details on safety assessments and AE/SAE reporting. 
j.) Concomitant medications and nondrug therapies must be reported starting with signing of informed consent and ending 28 days after the last dose. If the subject experiences an 
AE / SAE before the end of the final safety phone call (60 days after last dose), concomitant medications and nondrug therapies may also be collected, if part of the treatment of 
the AE/SAE. 
k.) If a DLCO is available within 3 months prior to screening, it can be utilized for screening purposes. 
l.) On-treatment PFTs, should be collected pre-dose. 
m.) If a recent HRCT scan (within 3 months prior to screening) is available, it can be utilized for screening purposes, provided it is submitted and evaluated by the Independent 
Radiology Imaging Review Group, is adhering to the same imaging acquisition parameters detailed in the Imaging Core Manual (ICM), and is either using the same accredited 
scanner, or is performed using the same modality, as the on-study HRCT scans. 
n.) Questionnaires are obtained pre-dose. On weeks where both questionnaires and PFTs are obtained, PFT should be completed first.  
o.) Pregnancy tests for woman of childbearing potential (WOCBP) only: serum pregnancy test at Screening; urine pregnancy tests (pre-dose) during study visits. A positive urine 
pregnancy test must be confirmed by serum hCG. At 60 days after last dose, a urine pregnancy test to be done at home by the subject (WOCBP) and report result to site. In each 
case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is strongly recommended. This recommendation also applies to 
WOCBP with infrequent or irregular menstrual cycles. 
p.) Urine pregnancy test to be done at Week 48 visit for woman of child bearing potential only, who consent to OLE. A positive urine pregnancy test must be confirmed by serum 
hCG. 
q.) ET subjects will  be contacted by phone at weeks 24 and 48 to check the subject’s vital status. 
r.) All subjects will attend a visit 28 days after the last dose for all the marked assessments, and will be contacted by phone 60 days after the last dose, for a final safety assessment. 
Note: These two final safety assessments are to be scheduled after the last, final dose of study drug (e.g.: for subjects not progressing to the optional, OLE phase, the last dose is 
the one received during double blind phase; for subjects continuing in the OLE, it is the last pamrevlumab dose in the OLE phase). The visit window for safety follow up period 
are: 28 days + 7 days and 60 days + 7days (phone call) after the last dose. If the subject experiences an SAE during these 60 days, it must be reported within 24 hours of awareness 
(see Section 7.3 for details).   
s.) Subjects eligible for the OLE are to be consented for the OLE at or before the Week 48 visit  
t.) ET subjects: PFTs and Questionnaires do not have to be repeated if the last one was performed within 8 weeks (excluding the screening visit) of the ET visit.HRCT does not 
have to be repeated if the last one  performed was within 4 months (excluding the screening visit) of the ET visit. Subjects who terminate / withdraw from the study early, for any 
reason, will have an Early Study Termination (ET) visit as soon as feasible. IP infusion will not be done at the ET visit. 
u.) For Czech Republic only: TB test done locally at screening only if none was performed within 6 months before screening for the study. 
v.) For Czech Republic only: For the first three infusions, the post-infusion observation period is 2 hours 


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APPENDIX 2. PHARMACOKINETIC, BIOMARKER, 
IMMUNOGENICITY AND GENOMICS SAMPLING 
Timepointa 
PKg 
(Plasma) 
Biomarkers b,f 
(Serum and plasma) 
CTGF b 
(Plasma) 
HAHA/HAHA-
NAe(Plasma) 
Genomics 
b,g 
(Whole blood) 
Tryptase 
(serum) 
Day 1 
Xc 
X 
X 
Xb 
X 
 
Day 8 
Xd 
 
 
Day 15 
Xd 
 
 
Week 3 
Xc 
 
 
Week 12 
Xc 
 
 
Week 24 
Xc 
X 
X 
Xb 
 
 
Week 36 
Xc 
X 
Xb 
 
Week 48 /Last 
dose/ET 
Xc 
X 
Xe 
Xb 
 
28 days after Last dose 
Xd 
X  
X f 
X b 
 
Suspected  
Hypersensitivity/ 
Anaphylactic Reaction 
 
Xh 
 
Xh 
Xh 
 
Xh 
Abbreviations: PK = Pharmacokinetic; CTGF = connective tissue growth factor; HAHA = human anti-human 
antibody; HAHA-NA = human anti-human antibody neutralizing antibody; ET = Early Termination 
a.) For all time points, the actual date and time of sample collection must be recorded, in addition to date and time of 
study treatment administration. 
b.) Sample should be collected within 2 hours prior to dosing start. 
c.) Both pre-dose and post-dose samples are required for PK.  Pre-dose sample collection should be within 2 hours 
prior to dosing and post-dose should be between 1-4 hours after dosing end.  
d.) Only one sample is required.  A ±2 day window may be applied to the Day 8 and 15 sample. 
e.) Samples with positive HAHA results will be tested for neutralizing antibody (HAHA-NA). 
f.) Biomarkers will be collected in countries where the Regulatory Agencies allow collection of these samples.  
g.) PK and DNA samples will be collected for subjects who consent, except in countries where the Regulatory 
Agencies do not allow collection of these samples 
h.) In the event of a suspected hypersensitivity/anaphylactic reaction, PK, HAHA, HAHA-NA, CTGF and tryptase 
samples should be collected. The Tryptase sample should be drawn within 1 to 6 hours of immunogenic reaction, 
and all other samples should be collected within 24 hours of the immunogenic reaction. 
 


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APPENDIX 3. HRCT CRITERIA AND HISTOPATHOLOGICAL 
CRITERIA FOR UIP PATTERN 
HRCT Criteria for UIP Pattern 
UIP Pattern 
• Subpleural and basal predominant; distribution is often heterogeneous¹ 
• Honeycombing with or without peripheral traction bronchiectasis or bronchiolectasis² 
Probable UIP Pattern 
• Subpleural and basal predominant; distribution is often heterogeneous 
• Reticular pattern with peripheral traction bronchiectasis or bronchiolectasis 
• May have mild ground-glass opacities (GGO) 
Indeterminate for UIP 
• Subpleural and basal predominant• Subtle reticulation; may have mild GGO or 
distortion (“early UIP pattern”) 
• CT features and/or distribution of lung fibrosis that do not suggest any specific 
etiology (“truly indeterminate for UIP”) 
Histopathological Criteria for UIP Pattern 
UIP Pattern  
• Dense fibrosis with architectural distortion (i.e., destructive scarring and/or 
honeycombing) 
• Predominant subpleural and/or paraseptal distribution of fibrosis 
• Patchy involvement of lung parenchyma by fibrosis 
• Fibroblast foci 
• Absence of features to suggest an alternate diagnosis 
Probable UIP Pattern 
• Some histologic features from column 1 are present but to an extent that precludes a 
definite diagnosis of UIP/IPF AND 
• Absence of features to suggest an alternative diagnosis OR 
• Honeycombing only 
Indeterminate for UIP Pattern 
• Fibrosis with or without architectural distortion, with features favoring either a 
pattern other than UIP or features favoring UIP secondary to another cause³ 
• Some histologic features from column 1, but with other features suggesting an 
alternative diagnosis⁴ 
¹ Variants of distribution: occasionally diffuse, may be asymmetrical. 
² Superimposed CT features: mild GGO, reticular pattern, pulmonary ossification. 


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³ Granulomas, hyaline membranes (other than when associated with acute exacerbation of IPF, which may be the 
presenting manifestation in some patients), prominent airway-centered changes, areas of interstitial inflammation 
lacking associated fibrosis, marked chronic fibrous pleuritis, organizing pneumonia. Such features may not be overt 
or easily seen to the untrained eye and often need to be specifically sought. 
⁴ Features that should raise concerns about the likelihood of an alternative diagnosis include a cellular inflammatory 
infiltrate away from areas of honeycombing, prominent lymphoid hyperplasia including secondary germinal centers, 
and a distinctly bronchiolocentric distribution that could include extensive peribronchiolar metaplasia. 


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APPENDIX 4. RADIATION RISK ASSESSMENT 
The estimated radiation dose that results from participation in this study is based on an estimate 
is for a “standard patient” such as the MIRD phantom used in the ImPACT dose calculator 
spreadsheet. However, the ImPACT spreadsheet does not have a model for all CT platforms and 
for these the DLP*k method is used. For this method we assume a “standard sized” patient 
model, scan length is 25 cm (the length of the lungs for the MIRD Phantom) and a k factor of 
0.014 mSv/mGy*cm for a thoracic scan (AAPM report 96 and European Guidelines 2000). For 
this study the expected doses are summarized in the table below. 
Please NOTE that for each visit, one CT exam will be performed. That exam will consist of a 
required scan per imaging manual. Effective dose estimates provided: (For this study, visits 
occur at Baseline, Week 24 and Week 48 (i.e. 3 visits).  Early Term scan is not required if a 
previous scan was completed within 4 months (excluding screening visit) of the ET visit.    
Summary 
 
TLC scan – CTDIvol 
6.1 mGy 
TLC scan – DLP (25 cm scan) 
153 mGy*cm 
TLC scan only – DLP 
153 mGy*cm 
Effective Dose per CT exam (TLC only) 
2.14 mSv per exam 
Effective Dose per year (TLC only) (assume 2 studies each 
calendar year) 
4.28 mSv per year 
Effective Dose over entire study (TLC only) (3 studies) 
6.42 mSv over entire study 
For a comparison, the average annual exposure from background radiation (excluding medical 
exposure to population): 
Based on National Average: 
 
United States 
3.0 mSv per year 
Canada 
1.8 mSv per year 
United Kingdom 
2.5 mSv per year 
Australia 
2.0 mSv per year 
Germany 
2.0 mSv per year 
India 
2-2.5 mSv per year 
References: 
ImPACT http://www.impactscan.org/ctdosimetry.htm 


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AAPM - American Association of Physicists in Medicine (2008). The measurement, Reporting 
and Management of Radiation Dose in CT. Report No. 96 of AAP M Task Group 23, (2008) 
European Commission (2000). European guidelines on quality criteria for computed 
tomography. EUR 16262 EN. Luxembourg, Office for Official Publications of the European 
Communities. 
U.S. NRC Fact Sheet on Biological Effects of Radiation 
 
 
 


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APPENDIX 5. GAP SCORE CALCULATION 
NOTE:  For the screening FVCpp value and GAP score calculation: the quality-controlled, Best-
Test Review (BTR) assessment provided by the spirometry vendor over-reader, which is 
provided to sites within 48 hours after uploading the test, is to be used for eligibility assessment 
and GAP score calculation.  
Use the FVCpp and DLCOpp that qualifies the subject for the study entry during screening 
https://www.mdcalc.com/gap-index-idiopathic-pulmonary-fibrosis-ipf-mortality 
 
GAP STAGE CALCULATION  
(GAP Stage is derived from the GAP Score taken during screening) 
Points 
Gender 
Female 
0 
Male 
1 
Age 
≤ 60 years 
0 
61-65 years 
1 
> 65 years 
2 
Predicted Forced Vital 
Capacity (FVCpp)  
> 75% 
0 
50-75% 
1 
< 50% 
2 
Predicted Diffusing Capacity 
of the Lung for Carbon 
Monoxide (DLCOpp)  
> 55% 
0 
36-55% 
1 
≤ 35% 
2 
Unable to 
perform 
3 
Total possible points 
8 
Stage 
Points 
Stage I 
0-3 
Stage II 
4-5 
Stage III 
6-8 


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APPENDIX 6. OPTIONAL, OPEN LABEL EXTENSION (OLE) PHASE 
OF PAMREVLUMAB 
Objective: 
The objective of this open-label extension (OLE) phase is to evaluate the long-term safety of 
pamrevlumab in subjects with idiopathic pulmonary fibrosis (IPF). 
This is an optional, open-label, single arm extension phase to provide continued access to 
pamrevlumab in subjects with IPF who completed the Week 48 visit of the main study and wish 
to participate in this OLE. 
 
Efficacy Assessment: 
The following efficacy assessments will be collected only as standard-of-care per each 
investigational site’s real world practice and descriptively presented during the OLE period: 
• FVC (L) 
• FVC percent predicted (pp) 
• Absolute FVCpp decline of ≥10%  
• All-cause mortality 
• Respiratory hospitalizations 
• Acute IPF exacerbations  
• Change in HRCT Quantitative Lung Fibrosis (QLF) volume (if HRCT is performed 
as part of routine patient care) 
 
Safety Assessments: 
Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events 
(TESAEs; including hypersensitivity/anaphylactic reactions) will be collected for 60 days after 
the last dose.  
In addition, pre- and post-infusion vital signs and immunogenicity (Human Anti-Human Antibody 
[HAHA] formation) testing will be collected. 
 
Design 
This is a multi-center, single-arm, open-label extension (OLE) phase in which subjects who 
complete the Week 48 visit of the main study are eligible to participate, as per Eligibility 
Assessments below.   
All subjects will receive pamrevlumab in an open-label manner. NOTE: No unblinding of 
subject’s treatment assignment in the main study will occur for purposes of OLE participation.  
During the OLE treatment period, co-administration of an approved IPF therapy (i.e., pirfenidone 
or nintedanib) is acceptable if clinically indicated in the Investigator’s opinion, provided that the 
Investigator assesses the potential risks/benefits of combining approved IPF therapies with 
pamrevlumab. See also Section 5.1.10 of the main study for details. 


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Eligibility Assessments: 
All subjects participating in the OLE phase must have completed the Week 48 visit of the main 
study. In addition, the Investigator must consider the subject to be suitable for continued 
participation in this phase, including ability to comply with study visits every 3 weeks for 
pamrevlumab infusions.  
A signed and dated IRB/IEC-approved informed consent must be obtained before dosing start, 
and preferably on or before the Week 48 visit of the main study.   
Male subjects with partners of childbearing potential and female subjects of childbearing 
potential (including those <1 year postmenopausal) must continue to use highly effective 
contraception methods (per Section 5.2.3) until 3 months after the last dose of study drug in the 
OLE phase.  
Additional consideration for participation in the OLE 
The following conditions are excluded for continued participation in this OLE phase: 
• Female subjects who are pregnant or nursing. 
• Use of any investigational drugs, or participation in a clinical trial with an investigational 
new drug, other than participation in the main study. 
• History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies, or experienced an allergic or anaphylactic reaction to study drug 
or to any component of the excipient while participating in the main study. 
• Subjects who withdrew informed consent while participating in the main study. 
• The Investigator judges that the subject is not suitable for participation, or is unable to 
fully participate in the OLE phase and complete it for any reason, including inability to 
comply with study procedures and treatment, or any other relevant medical or psychiatric 
conditions 
Study Duration 
The OLE phase will end either after the last subject completes 48 weeks of treatment, or 
pamrevlumab is commercially for the indication of IPF, or the Sponsor decides to end the OLE 
phase, whichever occurs first. 
Subjects may withdraw from the OLE at any time, for any reason. Such subjects will have an 
early termination visit (EX ET) as soon as feasible. Study procedures to be performed during the 
EX ET visit can be found in the OLE Schedule of Assessments (SOA) presented in Appendix 6. 
Also these subjects will have  a Safety Follow-Up Visit 28 days after the last dose and a final 
follow-up safety phone call 60 days after the last dose. 
Any assessments repeated as a part of main study, and all AEs prior to first dose in OLE are 
considered part of the main study. 
Study Drug Dosing instructions and Visit Schedule 
Each subject will receive pamrevlumab (30 mg/kg) every 3 weeks, using the weight obtained on  
Day 1 of the OLE phase (=EX Day 1), and every 24 weeks thereafter, for assessment of the 
proper weight-based dosing regimen. EX Day 1 is expected to be scheduled 3 weeks ±7 days 
after the Week 48 visit of the main study.  


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See Protocol Section 5 for detailed information on study drug infusions.  Home infusions via 
home health care (HHC) may be available during the OLE phase of the study at the discretion of 
the Investigator but such home infusions services will not be reimbursed by the Sponsor. Any 
home infusions via home health care are not permitted until at least three infusions in the OLE period 
have been administered without safety concerns.  
Subjects who experience a significant infusion-associated AE may not receive HHC. In addition, if a 
new safety concern arises during a home infusion, the subject has to attend an on-site visit for an 
Investigator assessment as soon as feasible. 
Medications and supplies to treat suspected hypersensitivity/anaphylactic reactions must be available 
for immediate use for all study drug infusion visits. 
Important NOTE: The infusion durations and post-infusion observations periods have to be 
followed per Table 1 in Protocol Section 5.1.6, including the initial dosing and observations 
periods. This is to ensure that subjects transitioning from placebo (in the double blinded phase) 
receive adequate safety monitoring during OLE. 
Visit windows are within ±7 days of the scheduled visit date from OLE (EX) Week 3 through 
last dose in the OLE; however, visits should be at least 10 days apart, to ensure intervals of at 
least 10 days between study drug infusions. 
All study visits will be performed in accordance with the OLE Schedule of Assessments (SOA) 
presented in Appendix 6. 
Missed Visits/Missed Doses 
Scheduled visit dates are determined from the time of the first dose in OLE, which is defined as 
EX Day 1. If a subject misses a visit, the subject should resume the regular visit schedule at the 
next scheduled visit.  
Missed doses are not to be made up through extra visits. If a subject misses more than two 
infusions in any 18-week period, or two sequential infusions, the FibroGen Medical Monitor 
should be notified.  The reason for missed doses must be documented in the subject’s clinical 
record. 
NOTE: In accordance with FDA/EMA Guidance: During the COVID-19 pandemic, the visit 
modality (e.g.: in-person versus remotely) and scheduling maybe adjusted and conducted at the 
discretion of the Investigator, in accordance with the site’s rules and recommendations, and 
using all necessary precautions. If a visit has to be done remotely, it can be conducted with any 
technology available to the site and study subjects.   
Unscheduled Visits 
Unscheduled visits/assessments will be captured accordingly in the clinical database 
Subject Study Withdrawal Criteria 
Subjects may withdraw from the OLE at any time, for any reason. Such subjects will have an 
early termination visit (EX ET) as soon as feasible. Study procedures to be performed during the 
EX ET visit can be found in the OLE Schedule of Assessments (SOA) presented in Appendix 6. 
Reasons for withdrawal will be captured on CRF.   


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Mandatory reasons for withdrawing from the OLE phase include:  
• Any safety concern in the Investigator’s opinion, that precludes further study 
participation 
• Lung transplant 
• Pregnancy 
• Withdrawal of Consent  
Safety Follow-Up 
All subjects will have two Safety Follow-Up Visits: 
• 28 days  after the last dose 
• 60 days after last dose: follow-up phone call, for a final safety assessment   
The visit windows for the safety assessments are: 28 days +7 days and 60 days +7 days (phone 
call) after the last dose. 
See OLE SOA in Appendix 6. 
After the protocol-required reporting period (60 days after the last dose), the Investigator does 
not need to actively monitor subjects for SAEs.  However, if the Investigator becomes aware of 
an SAE/death that may be possibly related to study treatment after the protocol-required 
reporting period, the Investigator may report the event to FibroGen as outlined in Section 7 of 
the main study. SAEs reported outside of the protocol-required reporting period will be captured 
within the safety database only as clinical trial cases for the purposes of expedited reporting. 
Study Assessments: 
All study assessments are done per the local standard of care with the exception of weight, pre 
and post infusion vital signs and pregnancy test. Refer to OLE SOA for details. 
Vital Signs (including Weight) – Pre and Post pamrevlumab infusion 
Vital signs to be collected include heart rate, blood pressure and temperature:   
• Heart rate should be collected as beats/min 
• Systolic and diastolic blood pressure should be collected from subjects in seated 
position (mmHg) 
• Temperature should be taken as oral or tympanic and captured as °F or °C 
Weight is collected at EX Day 1 and every 24 weeks thereafter for purposes of adjusting the 
weight-based dose if necessary. 
Laboratory Evaluations 
Local lab results, done as part of local standard-of-care, will not be recorded on CRF; local lab 
results will be reviewed by the Investigator for clinical significance and to determine appropriate 
reporting of adverse events (see Section 7.3.7 of the main study).  
Pregnancy tests (performed pre-dose EX Day 1, and at other study visits) apply only for women 
of childbearing potential (WOCBP).  Urine pregnancy test should be done by the site using site 
supplies. A positive urine pregnancy test must be confirmed by serum hCG using the site local 
labs for testing. At 60 days after last dose, a urine pregnancy test to be done at home by the 


Pamrevlumab 
Protocol FGCL-3019-095 PA 2.0 
 
 
Confidential 
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subject (WOCBP) and report result to site. In each case of delayed menstrual period (over one 
month between menstruations) confirmation of absence of pregnancy is strongly recommended. 
This recommendation also applies to WOCBP with infrequent or irregular menstrual cycles. 
PFTs and HRCT 
PFTs and HRCTs are performed locally, and at a frequency according to local SOC, as 
determined by the Investigator. These tests will not be reimbursed by Sponsor. 
All local spirometry results are entered into EDC. 
If HRCT scans are done, they should be uploaded to the same Independent Radiology Review 
Group as for the main study.  
Human Anti-Human Antibodies (HAHA) 
Plasma samples will be collected for evaluation of human anti-human antibodies (HAHA), in all 
subjects participating in the OLE at the 28 days after last dose Safety Follow-Up Visit. A 
specialty laboratory will measure HAHA titers using a validated assay.   
Samples with positive HAHA results will be tested for neutralizing antibody (HAHA-NA). The 
prevalence and duration of binding and neutralizing antibodies and the effect of these antibodies 
on the pharmacokinetics, pharmacodynamics markers, efficacy, and safety of pamrevlumab will 
be assessed. 
Suspected Hypersensitivity or Anaphylactic Reactions 
Any immunogenic reactions, including drug-related hypersensitivity or anaphylaxis, should have 
PK, HAHA, HAHA-NA, CTGF and tryptase drawn within 24 hours of a suspected reaction from 
pamrevlumab (see OLE PHARMACOKINETIC, CTGF AND IMMUNOGENICITY 
SAMPLING SCHEDULE OF ASSESSMENTS for more detail). 
This will not be considered optional for the subject unless there is local institutional guideline 
consideration for total blood volume collection on the same day as a standard blood draw 
timepoint, which could preclude the subject from having this collection take place within 24 
hours. The Tryptase sample should be drawn within 1 to 6 hours of immunogenic reaction, and 
all other samples should be collected within 24 hours of the immunogenic reaction. See OLE 
PHARMACOKINETIC, CTGF AND IMMUNOGENICITY SAMPLING SCHEDULE OF 
ASSESSMENTS for more detail. 
Statistical Considerations: 
Data collected during the extension period will be summarized descriptively. 
 
 


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OLE Schedule of Assessments 
 
Abbreviations: AE = adverse event; SAE = serious adverse event; hCG = human chorionic gonadotropin; HRCT = 
high resolution computed tomography; PFTs = Pulmonary Function Test; (SOC) = not required at time-points noted 
above, but assessed per timing of local standard of care; EX = Extension; WOCBP = Woman of child bearing 
potential; HAHA = human anti-human antibody; HAHA-NA = human anti-human antibody neutralizing antibody 
EX ET = Extension Early Termination 
 
a.) EX Day 1 is expected to be scheduled 3 weeks ±7 days after the Week 48 visit of the main study. Pamrevlumab 
is dosed Q3W starting with EX-Day 1. Visit windows of ±7 days, EX Week 3 through Follow-Up Period. Missed 
visits are not to be made up between scheduled visits, subject is to return for the next scheduled visit 
b.) Unscheduled visit assessments (procedures) will be determined by the investigator.  During the COVID-19 
pandemic, the visit modality (e.g.: in-person versus remotely) and scheduling maybe adjusted and conducted at the 
discretion of the Investigator, in accordance with the site’s rules and recommendations, and using all necessary 
precautions. If a visit has to be done remotely it can be conducted with any technology available to the site and study 
subjects.    
c.) Ensure subject has signed the informed consent at or before Week 48 visit of the main study and eligibility 
considerations have been assessed prior to EX Day 1 infusion. 
d.) Weight will be measured at EX Day 1 and every 24 weeks thereafter to determine dose for the subsequent 24-
week interval. 
e.) Infusions must be at least 10 days apart. Vital signs (blood pressure, pulse, and temperature) must be recorded 
prior to, and after each infusion. The infusion durations and post-infusion observations periods have to be followed 
per Table 1 in Protocol Section 5.1.6, including the initial dosing and observations periods. Any home infusions via 
home health care are not permitted until at least three infusions in the OLE period have been administered without 
safety concerns. If a new safety concern arises during a home infusion, the subject has to attend an on-site visit for 
an Investigator assessment as soon as feasible. 
 
Dosing Period a, b 
Follow-Up Period o 
Study Week 
EX-Day 1c 
Q3 
Weeks 
Q24o 
Weeks /Last 
dose/EX ETp 
28 days 
after Last 
dose n 
60 days 
(phone call) 
after Last 
dose n 
Assessment 
 
 
 
 
 
Weight  
X d 
 
X d 
 
 
Vital Signs e 
X 
X 
X 
X 
 
Infusions e 
X 
X 
X q 
 
 
AEs/SAEs f 
X 
X 
X 
X 
X 
Concomitant 
Medications g 
X 
X 
X 
X 
X g 
Procedures and 
Nondrug Therapies g 
X 
X 
X 
X 
X g 
PFTs (local) h, i, j  
SOC 
 
SOC 
 
 
Labs (local) h, i, k 
SOC 
 
SOC 
SOC 
 
HRCT of Chest i, l 
SOC 
 
SOC 
 
 
Pregnancy Test (urine) 
(WOCBP) m 
X 
X 
X 
X 
Xm 


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Page 93 of 93 
f.) See Section 7 of the main protocol for safety assessments. 
g.) Concomitant medications and nondrug therapies are recorded after signing of informed consent and ending 28 
days after the last dose. If the subject experiences an AE or SAE before the end of the final safety phone call (60 
days after last dose), concomitant medications and nondrug therapies may also be collected, if part of the treatment 
of the AE/SAE. 
h.) Local Labs and PFTs are performed pre-dose. 
i.) Collected according to local standard of care.  
j.) PFT will be done locally, and at a frequency per local SOC, and recorded on CRF whenever they are performed 
locally.  
k.) Labs will be done locally and at a frequency per local SOC. Lab data will NOT be recorded on CRF. Clinically 
significant laboratory abnormalities will be reported in the context of AE reporting; do not report non-clinically 
significant lab abnormalities as AE 
l.) HRCT scans will be performed at a frequency per local SOC. Any HRCT scan will be uploaded to central HRCT 
radiology vendor  
m.) Pregnancy tests (performed pre-dose EX Day 1, and at other study visits) only apply for WOCBP, and are to be 
performed via urine pregnancy test. A positive urine pregnancy test must be confirmed by serum hCG. At 60 days 
after last dose, a urine pregnancy test to be done at home by the subject (WOCBP) and report result to site. In each 
case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is 
strongly recommended. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycles. 
n.) Subjects should attend a Safety Follow-Up visit 28 days after the last dose. These subjects will also be contacted 
by phone for a Safety Follow-Up callat 60 days after the last dose for a final safety assessment. The visit window for 
safety follow up period are: 28 days + 7 days (visit) and 60 days + 7days (phone call) after the last dose. If the 
subject experiences an SAE, it must be reported within 24 hours of awareness (see Section 7.3 for details). 
o.) The OLE phase will end either after the last subject completes 48 weeks of treatment, or pamrevlumab is 
commercially for the indication of IPF, or the Sponsor decides to end the OLE phase, whichever occurs first  
p.) Subjects who terminate / withdraw from the OLE phase for any reason, will have an Extension Early Study 
Termination (EX ET) visit as soon as feasible. IP infusion will not be done at the EX ET visit 
 
 
OLE PHARMACOKINETIC, CTGF AND IMMUNOGENICITY SAMPLING 
SCHEDULE OF ASSESSMENTS 
 
Timepoint  
PK 
(Plasma) 
CTGF  
(Plasma) 
HAHA/HAHA-NA 
(Plasma) 
Tryptase 
(serum) 
28 days after Last Dose 
 
 
Xa 
 
Suspected  
Hypersensitivity/ 
Anaphylactic Reaction 
Xb 
Xb 
Xb 
Xb 
Abbreviations: PK = Pharmacokinetic; CTGF = connective tissue growth factor; HAHA = human anti-human antibody; 
HAHA-NA = human anti-human antibody neutralizing antibody 
a.) All subjects participating in the OLE will have a HAHA sample taken 28 days after the last dose. Samples 
with positive HAHA results will be tested for neutralizing antibody (HAHA -NA) assays and analyses 
b.) In the event of a suspected hypersensitivity/anaphylactic reaction, PK, HAHA, HAHA-NA, CTGF and 
tryptase samples should be collected. The Tryptase sample should be drawn within 1 to 6 hours of immunogenic 
reaction, and all other samples should be collected within 24 hours of the immunogenic reaction. 
 


Signature Page for VV-CLIN-013474 v1.0
Signature Page for VV-CLIN-013474 v1.0
Approval Task
14-Jan-2023 15:45:49 GMT+0000

SAP_001.pdf: 
FibroGen, Inc. 
Confidential and Proprietary 
Page 1 of 16 
STATISTICAL ANALYSIS PLAN 
STUDY TITLE: 
A Phase 3, Randomized, Double-Blind, Placebo-
Controlled Efficacy and Safety Study of 
Pamrevlumab in Subjects with Idiopathic 
Pulmonary Fibrosis (IPF) 
PROTOCOL NUMBER: 
FGCL-3019-095 (ZEPHYRUS 2) 
AMENDMENT 
VERSION: 
2.0 
SAP VERSION: 
Final V1.0 (OLE Period) 
RELEASE DATE: 
16Oct2023 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and proprietary to 
FibroGen, Inc. No part of this document or any of the information contained herein may 
be transmitted, disclosed, shared, reproduced, published, or utilized by any persons 
without prior written authorization by FibroGen, Inc. 
NCT #: NCT04419558


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 2 of 16 
SIGNATURE PAGE 
Approvals 
I have reviewed and accepted the information in this document to be a true and accurate 
representation of the Statistical Analysis Plan. 
*Signature: see appended final page for 21CFR Part 11 compliant approval 
Initiator: 
  
 FibroGen, Inc. 
Reviewed by: 
 
, FibroGen, Inc. 
 
, FibroGen, Inc. 
 
, FibroGen, Inc. 
 
 FibroGen, Inc. 
  
, FibroGen, Inc. 
 
, FibroGen, Inc. 
 
, FibroGen, Inc. 
Signature Significance 
The following significance is lent to the signatures on the Approvals page of this document. 
Signatory 
Significance 
Initiator 
By signing, the author is attesting that the content of the document is 
complete and accurate. 
Reviewer 
By signing, the reviewer is attesting that the document’s approach and 
contents are compliant with the study protocol, all appropriate, regulatory 
requirements, and other significant guidelines. This individual(s) has 
reviewed the document for accuracy and completeness. 
 
 
 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 3 of 16 
CHANGE HISTORY 
Version 
Date 
Description 
1.0 
16Oct2023 
Final Approved Version 
 
 
 
 
 
 
 
 
 
 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 4 of 16 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ................................................................................................1 
SIGNATURE PAGE .......................................................................................................................2 
CHANGE HISTORY.......................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................6 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
INTRODUCTION ........................................................................................................8 
2. 
STUDY OBJECTIVE ...................................................................................................8 
3. 
STUDY DESIGN (OLE PERIOD) ..............................................................................8 
3.1. 
Enrollment to OLE Period ............................................................................................8 
3.2. 
Randomization ..............................................................................................................8 
3.3. 
Study Periods ................................................................................................................8 
4. 
STUDY ENDPOINTS (OLE) ......................................................................................9 
5. 
GENERAL STATISTICAL CONSIDERATIONS ......................................................9 
5.1. 
Statistical Methodology ................................................................................................9 
5.1.1. 
Analysis of Categorical Endpoints ...............................................................................9 
5.1.2. 
Analysis of Continuous Endpoints ...............................................................................9 
5.1.3. 
Analysis of Spirometry Data ........................................................................................9 
5.1.4. 
Analysis of HRCT Data ................................................................................................9 
5.2. 
Analysis Set ................................................................................................................10 
5.2.1. 
Safety Analysis Set - OLE ..........................................................................................10 
5.2.2. 
Immunogenicity Analysis Set -OLE (IGS-OLE) .......................................................10 
5.3. 
General Data Handling Rules and Presentation Specifications ..................................10 
5.3.1. 
Analysis Period ...........................................................................................................10 
5.3.2. 
Baseline Definitions ....................................................................................................10 
5.3.3. 
Formulas .....................................................................................................................10 
5.3.4. 
General Instructions of TLF .......................................................................................11 
5.3.5. 
Handling Dropouts and Missing Data ........................................................................11 
5.4. 
Interim Analysis and Data Monitoring Committee ....................................................11 
6. 
STATISTICAL ANALYSIS ......................................................................................11 
6.1. 
Subject Accountability and Disposition .....................................................................11 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
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Confidential and Proprietary 
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6.2. 
Protocol Deviations ....................................................................................................11 
6.3. 
Demographics .............................................................................................................12 
6.4. 
Concomitant Medications ...........................................................................................12 
6.5. 
Treatments and Medications .......................................................................................12 
6.5.1. 
Study Drug Exposure ..................................................................................................12 
6.5.2. 
Treatment Compliance ................................................................................................12 
6.6. 
Efficacy Analysis ........................................................................................................12 
6.6.1. 
Efficacy Endpoint Analysis and Estimand .................................................................13 
6.6.1.1. 
Estimand Strategy .......................................................................................................13 
6.6.1.2. 
Population of Interest ..................................................................................................13 
6.6.1.3. 
Intercurrent Event Handling Strategy .........................................................................13 
6.6.1.4. 
Analysis Variable ........................................................................................................13 
6.6.1.5. 
Population Summary ..................................................................................................13 
6.7. 
Safety Analysis ...........................................................................................................13 
6.7.1. 
Adverse Events (AE) ..................................................................................................13 
6.7.2. 
Vital Signs ..................................................................................................................13 
6.8. 
ADA (Anti-Drug Antibody) Analysis ........................................................................13 
6.9. 
PK Analysis ................................................................................................................13 
7. 
CHANGES FROM PROTOCOL ...............................................................................14 
8. 
REFERENCE .............................................................................................................14 
Appendix 1. Analysis Visit Windows .........................................................................................15 
Appendix 2. Analysis of Association between QLF and OS ......................................................16 
 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 6 of 16 
LIST OF TABLES 
Table 1: 
Analysis Visit Window for Vital Signs ......................................................................15 
Table 2: 
Analysis Visit Window for PFT and Weight [#] ........................................................15 
Table 3: 
Analysis Visit Window for HRCT .............................................................................15 
 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 7 of 16 
LIST OF ABBREVIATIONS 
Abbreviation 
Explanation 
ADA 
Anti-Drug Antibody 
AE  
Adverse Event  
BMI 
Body Mass Index 
CI 
Confidence Interval 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
EDC 
Electronic Data Capture 
FVC 
Forced Vital Capacity 
FVCpp 
Forced Vital Capacity percentage predicted 
HAHA 
Human Anti-Pamrevlumab Antibody 
HRCT 
High-Resolution Computed Tomography 
IPF 
Idiopathic Pulmonary Fibrosis 
IV 
Intravenous 
L 
Liter 
mL 
milliliter 
OLE 
Open Label Extension 
PEY 
Patient Exposure Years 
PFT 
Pulmonary Function Test 
QLF 
Quantitative Lung Fibrosis 
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
TLF 
Table, Listing, and Figure 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 8 of 16 
1. 
INTRODUCTION 
This statistical analysis plan (SAP) is for the pre-specified reporting of study results for protocol 
FGCL-3019-095, amendment 2.0. This SAP documents the planned analyses only for the open-
label extension (OLE) period. Specifications of tables, data listings, and figures (TLF) are 
contained in a separate document. A separate SAP details the statistical analyses and methods for 
the double-blind period of FGCL-3019-095. 
In this document, only new definitions and rules will be described. Cross reference to the double-
blind SAP will be made for definitions and rules that will follow the same methodology used for 
the double-blind period of the trial. 
2. 
STUDY OBJECTIVE 
The overall objective of this Phase 3 registration-enabling study is to evaluate the efficacy and 
safety of 30 mg/kg intravenous (IV) infusions of pamrevlumab as compared to placebo in 
subjects with Idiopathic Pulmonary Fibrosis (IPF). The objective of the OLE phase is to evaluate 
the long-term safety of pamrevlumab in subjects with IPF, though efficacy assessments are 
included. 
3. 
STUDY DESIGN (OLE PERIOD) 
3.1. 
Enrollment to OLE Period 
Subjects who complete the Week 48 visit of the main study (regardless of the number of study 
drug infusions received) will be eligible to participate in the optional, OLE period of the study. 
The OLE period offers continuing access to pamrevlumab regardless of randomization 
assignment (pamrevlumab or placebo) in double-blind period of the study. Subjects will be 
considered as having entered the OLE study if they have received at least one dose of the study 
drug during the OLE period. 
3.2. 
Randomization 
Randomization is not applicable for the OLE period. 
3.3. 
Study Periods 
• Optional, OLE period of pamrevlumab: 
− Access to pamrevlumab will be available until the last subject completes 
48 weeks of treatment in the OLE period, or pamrevlumab is commercially 
available for the indication of IPF, or the Sponsor decides to end the OLE period, 
whichever occurs first. 
• Follow-up period/final safety assessments: 
− 28 days after the last dose 
− 60 days after the last dose: follow-up phone call, for a final safety assessment 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 9 of 16 
4. 
STUDY ENDPOINTS (OLE) 
The following efficacy and safety assessments will be collected only as standard-of-care per each 
investigational site’s real-world practice and descriptively presented during the OLE period: 
Efficacy assessments: 
• Forced vital capacity (FVC) (L) 
• FVC percent predicted (FVCpp) 
• Absolute FVCpp decline of ≥10% 
• All-cause mortality 
• Change in high-resolution computed tomography (HRCT) Quantitative Lung Fibrosis 
(QLF) volume (if HRCT is performed as part of routine patient care) 
Safety assessments: 
Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events 
(TESAEs; including hypersensitivity/anaphylactic reactions) will be collected for 60 days after 
the last dose. 
In addition, pre- and post-infusion vital signs and immunogenicity (Human Anti-Human 
Antibody [HAHA] formation) testing will be collected. 
5. 
GENERAL STATISTICAL CONSIDERATIONS 
5.1. 
Statistical Methodology 
All data collected will be included in the data listings. All analyses will be performed using 
SAS® Version 9.3 or higher. 
5.1.1. 
Analysis of Categorical Endpoints 
Follow the same guidelines as described in SAP for the double-blind period. 
5.1.2. 
Analysis of Continuous Endpoints 
Follow the same guidelines as described in SAP for the double-blind period. 
5.1.3. 
Analysis of Spirometry Data 
Follow the same guidelines as described in SAP for the double-blind period. 
5.1.4. 
Analysis of HRCT Data 
Follow the same guidelines as described in SAP for the double-blind period. 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
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Confidential and Proprietary 
Page 10 of 16 
5.2. 
Analysis Set 
5.2.1. 
Safety Analysis Set - OLE 
The Safety Analysis Set - OLE (SAF-OLE) includes all subjects who have received at least one 
study medication in the OLE period. Subjects will be analyzed according to the previous 
treatment actually received in the double-blind period. 
All analysis in OLE will be performed on SAF-OLE unless otherwise specified. 
5.2.2. 
Immunogenicity Analysis Set -OLE (IGS-OLE) 
The IGS-OLE will include all subjects who are in SAF-OLE, have baseline antidrug antibody 
(ADA) assessment in the double-blind period, and have at least one evaluable ADA assessment 
in the OLE period. 
5.3. 
General Data Handling Rules and Presentation Specifications 
5.3.1. 
Analysis Period 
• The primary analysis will be based on the on-study period which is defined as from 
Day 1 in the OLE period up to the end of the entire study, regardless of patients’ 
treatment status. 
5.3.2. 
Baseline Definitions 
Baseline is defined as the last assessment prior to the first dosing in the OLE period with 2 
exceptions below: 
• Baseline in the double-blind period and OLE will be applied for assessments of FVC 
and QLF; and 
• Baseline in the double-blind period will be applied for assessments of ADA. 
5.3.3. 
Formulas 
• Study Day Calculation 
− The day when a subject receives the first dose of study drug in the OLE period is 
designated as Day 1 in OLE. 
− Study day of an assessment/procedure is calculated as follows. 
 For assessments or procedures on Day 1 or later, 
Study day = assessment/procedure date – Day 1 date + 1. 
 For assessments or procedures earlier than Day 1, 
Study day = assessment/procedure date – Day 1 date. 
• Follow the same formulas as described in SAP for the double-blind period: 
− Body Mass Index (BMI) 
− Body weight, height, and temperature 
− (Absolute) Change from Baseline 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
FibroGen, Inc. 
Confidential and Proprietary 
Page 11 of 16 
− Relative change from baseline (%) 
• Patient exposure years (PEY) (on pamrevlumab in OLE period): 
− PEY = Number of subjects × Average Duration of Exposure, where duration of 
exposure is (date of last non-zero dose on pamrevlumab – date of first dose in 
OLE period on pamrevlumab + 1)/365.25. 
5.3.4. 
General Instructions of TLF 
Follow the same guidelines as described in SAP for the double-blind period. 
Summary tables will be presented for each previous actual treatment group in the double-blind 
period and all subjects pooled in the OLE period. 
Efficacy and safety data will be summarized descriptively for subjects who entered OLE. No 
formal statistical inference will be performed. 
5.3.5. 
Handling Dropouts and Missing Data 
For handling of dropouts and missing data the same guidelines will be followed as described in 
SAP for the double-blind period. No imputations will be performed on post-death analysis visits. 
5.4. 
Interim Analysis and Data Monitoring Committee 
In addition to routine safety monitoring, an independent Data Monitoring Committee (DMC) 
will be established to review safety data on an ongoing basis. A DMC charter will establish the 
procedures, meeting frequency, and scope of responsibilities of the committee. 
This study has no planned or pre-specified interim analysis for either efficacy or futility. 
6. 
STATISTICAL ANALYSIS 
6.1. 
Subject Accountability and Disposition 
The number (%) of subjects who entered the OLE period, discontinued prematurely from 
treatment, discontinued prematurely from study, and reasons for premature discontinuation will 
be presented for each previous treatment group in the double-blind period and all subjects 
pooled. 
Enrollment will also be summarized by study site. 
6.2. 
Protocol Deviations 
The number and percentage of subjects with important protocol deviations will be categorized 
and tabulated as appropriate. COVID-19 related important protocol deviations will be 
summarized in a separate table. All protocol deviations will be finalized prior to the OLE 
database lock. 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
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Confidential and Proprietary 
Page 12 of 16 
6.3. 
Demographics 
Demographic summaries will follow the same guidelines as described in SAP for the double-
blind period. 
6.4. 
Concomitant Medications 
Concomitant medications summaries will follow the same guidelines as described in SAP for the 
double-blind period. 
6.5. 
Treatments and Medications 
6.5.1. 
Study Drug Exposure 
Study treatment will be summarized for OLE period for SAF-OLE. 
• Duration of exposure in the OLE period = date last non-zero dose in the OLE period – 
date of the first dose in the OLE period + 1. 
Duration of study treatment in the OLE period will be summarized as a continuous variable and 
be tabulated by the categories as follows: 
• <12 weeks 
• 12 to <24 weeks 
• 24 to <48 weeks 
• 48 to <72 weeks 
• 72 to <96 weeks 
• ≥96 Weeks 
Number of infusions is defined as the number of non-zero dose infusions. 
The following dose administration parameters: 
• Total number of infusions in the OLE period (1-4, 5-8, 9-16, 17-24, 25-32, ≥33) 
• Overall average infusion doses (in mg/kg) in the OLE period 
• Whether infusion was interrupted and reason for interruption in the OLE period 
6.5.2. 
Treatment Compliance 
Follow the same guidelines as described in SAP for the double-blind period. 
6.6. 
Efficacy Analysis 
All analyses for efficacy endpoints will be performed for the SAF-OLE during the on-study 
period unless noted otherwise. 


FGCL-3019-095 (ZEPHYRUS 2)  
Statistical Analysis Plan  
Final V1.0 (OLE Period) 
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Confidential and Proprietary 
Page 13 of 16 
6.6.1. 
Efficacy Endpoint Analysis and Estimand 
6.6.1.1. 
Estimand Strategy 
The primary estimand is intended to provide a population-level assessment of the pamrevlumab 
on a continuous endpoint, regardless of participant compliance with the IP dosing. 
6.6.1.2. 
Population of Interest 
All subjects in SAF-OLE. 
6.6.1.3. 
Intercurrent Event Handling Strategy 
Treatment policy strategy will be used for any intercurrent event. No imputation on missing data. 
6.6.1.4. 
Analysis Variable 
Follow guidelines in SAP for the double-blind period. 
6.6.1.5. 
Population Summary 
Efficacy parameters, including change from baseline in FVC (L), FVCpp, and HRCT fibrosis 
score will be summarized descriptively at each scheduled visit as defined in Appendix 1. 
6.7. 
Safety Analysis 
The safety analyses will be performed for the SAF-OLE in the OLE period. 
6.7.1. 
Adverse Events (AEs) 
Follow the same guidelines as described in SAP for the double-blind period with additional PEY 
for OLE period on pamrevlumab will be provided. 
6.7.2. 
Vital Signs 
Follow the same guidelines as described in SAP for the double-blind period. The analysis visit 
window is defined in Appendix 1. 
6.8. 
ADA Analysis 
ADA analyses follow the same guidelines as described in SAP Part 1 for the double-blind period. 
Considering ADA assessment was collected only on 28 days after last dose in the OLE period, 
ADA incidence will be summarized on IGS-OLE. A listing with details will be provided for 
SAF-OLE. 
No subgroup analysis will be performed by ADA status. 
6.9. 
PK Analysis 
Not applicable for the OLE period. 


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7.
CHANGES FROM PROTOCOL
Respiratory hospitalization and acute IPF exacerbation endpoints have been removed in this 
095 OLE SAP, as adjudication of these events was only performed for the double-blind period of 
the study. 
8.
REFERENCE
•
E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and
Sensitivity Analysis in Clinical Trials
•
Jones PW, Forde, Y., St George’s Respiratory Questionnaire Manual.
http://www.healthstatus.sgul.ac.uk/SGRQ_download/SGRQ%20Manual%20June%2 
02009.pdf. Accessed June 2, 2020
•
Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in
idiopathic pulmonary fibrosis. N Engl J Med 2014; 370:2071-82.
•
Noble PW, Albera C, Bradford WZ, Costabel U, etc.; Pirfenidone in patients with
idiopathic pulmonary fibrosis (CAPACITY): two randomised trials; Lancet 2011;
377: 1760–69
•
Statistical Review and Evaluation for Ofev® (nintedanib) 150 mg capsules;
Indication: Treatment of Idiopathic Pulmonary Fibrosis (IPF); PDUFA: January 2,
2015 
•
King TE Jr., Bradford WZ, Castro-Bernardini S, etc.; A Phase 3 Trial of Pirfenidone
in Patients with Idiopathic Pulmonary Fibrosis; N Engl J Med 2014;370:2083-92.


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APPENDIX 1. ANALYSIS VISIT WINDOWS 
Analysis visits are defined by the windows that will have the widths of the corresponding 
assessments centered at the scheduled time. Unscheduled visits within a visit window defined 
below will be grouped into the closest scheduled visits based on the visit date. 
Table 1: 
Analysis Visit Window for Vital Signs  
Analysis Visit 
Target Day in OLE 
Start Day 
End Day 
Baseline  
See Section 5.3.2  
EX-Day 1 (postdose) [#] 
1 
1 
1 
EX-Week 3 (predose and postdose) 
22 
2 
32 
EX-Week 3*n (predose and postdose) 
21*n+1 
21*n-9 
21*n+11 
EX-28 Days post last dose [@] 
 
 
** 
** end of OLE period 
[$] n is 2, 3, 4, etc. 
[@] Same as visit collected on CRF. 
 
Table 2: 
Analysis Visit Window for PFT and Weight [#] 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline  
See Section 5.3.2 
EX-Week 24 
169 
2 
253 
EX-Week 24*n [$] 
24*n+1 
24*7*n-82 
24*7*n+85 
[$] n is 2, 3, 4, etc. 
Note: The timing of PFT is dependent on local schedules. 
[#] Weight baselines follow same rules as vital signs. 
 
Table 3: 
Analysis Visit Window for HRCT 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
See Section 5.3.2 
EX-Week 24 
169 
2 
253 
EX-Week 24*n [$] 
24*n+1 
24*7*n-82 
24*7*n+85 
EX-28 days Post last dose [@] 
 
 
** 
** end of OLE period 
[$] n is 2, 3, 4, etc. 
[@] Same as visit collected on CRF. 
Note: The timing of HRCT is dependent on local schedules. 


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APPENDIX 2. ANALYSIS OF ASSOCIATION BETWEEN QLF AND OS  
Cox proportional hazard (PH) analyses on the association between QLF and overall survival 
(OS) will be performed for the ITT population including both double-blind and OLE periods. 
The hazard ratio and its corresponding 95% CI between QLF Test Group vs QLF Reference 
Group. A stratified log-rank test stratified by randomization stratification factor will be used for 
treatment comparison. 
No imputation will be performed on missing data. On-treatment analysis will be optional. 
• QLF as a predictor: 
1. To investigate whether baseline QLF is a significant predictor of mortality, a Cox PH 
model will include electronic data capture (EDC) GAP stage (I/II/III), and prior IPF 
treatment (Yes/No) as covariates, baseline QLF% (cutoff such as 15%, 20%, or 25%) as 
the predictor variable. 
2. Similar analysis on baseline QLF volume (ml) will be performed as in 1), using baseline 
QLF volume (ml) (cutoff such as 300ml, 400ml, and 500ml) as the predictor variable. 
3. In addition, Cox PH model including EDC GAP stage (I/II/III), and prior IPF treatment 
(Yes/No) as covariates, baseline QLF% or QLF volume (ml) (as a continuous variable) as 
the predictor variable, will be performed. 
• Change from baseline in QLF at Week 24 as a predictor 
1. In addition, to investigate the association between change from baseline in QLF% 
(baseline to Week 24) and OS, the Cox PH model will include EDC GAP stage (I/II/III), 
prior IPF treatment (Yes/No), and baseline QLF% (as a continuous variable) as 
covariates, and category in change from baseline in QLF% (e.g., ≥2% vs <2%) as the 
predictor variable. 
2. Similar analysis on QLF volume (ml) change from baseline will be performed as in 4) 
with baseline QLF% replaced with baseline QLF volume as a continuous covariate, and 
change from baseline in QLF volume (ml) as the predictor variable with a cutoff (e.g., 
≥40 mL vs <40mL) will be performed. 


 
 
 
 
Confidential 
 
STATISTICAL ANALYSIS PLAN 
TITLE PAGE 
 
STUDY TITLE: 
A Phase 3, Randomized, Double-Blind, Placebo-
Controlled Efficacy and Safety Study of Pamrevlumab in 
Subjects with Idiopathic Pulmonary Fibrosis (IPF) 
PROTOCOL NUMBER: 
FGCL-3019-095 (ZEPHYRUS 2) 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
STUDY DRUG:  
Pamrevlumab 
INDICATION: 
Idiopathic Pulmonary Fibrosis (IPF) 
PROTOCOL VERSION: 
Version 2.0 
SAP VERSION 
Final V1.0 (Double-Blind Period) 
RELEASE DATE: 
12Jun2023 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and proprietary to FibroGen, 
Inc. No part of this document or any of the information contained herein may be 
transmitted, disclosed, shared, reproduced, published, or utilized by any persons without 
prior written authorization by FibroGen, Inc. 


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SIGNATURE PAGE 
Approvals 
I have reviewed and accepted the information in this document to be a true and accurate 
representation of the Statistical Analysis Plan. 
*Signature: see appended final page for 21CFR Part 11 compliant approval 
Initiator: 
 
, FibroGen, Inc. 
Reviewed by: 
 
, FibroGen, Inc. 
 
, FibroGen, Inc. 
 
 FibroGen, Inc. 
 
FibroGen, Inc. 
  
, FibroGen, Inc. 
 
, FibroGen, Inc.  
 
, FibroGen, Inc. 
 
 FibroGen, Inc. 
Signature Significance 
The following significance is lent to the signatures on the Approvals page of this document. 
Signatory Significance 
Initiator 
By signing, the author is attesting that the content of the document is complete 
and accurate. 
Reviewer 
By signing, the reviewer is attesting that the document’s approach and contents 
are compliant with the study protocol, all appropriate, regulatory requirements, 
and other significant guidelines. This individual(s) has reviewed the document for 
accuracy and completeness. 


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CHANGE HISTORY 
Version Date 
Description 
1.0 
12Jun2023 
Final Approved Version 
 
 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
CHANGE HISTORY.......................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................7 
LIST OF FIGURES .........................................................................................................................8 
LIST OF ABBREVIATIONS ..........................................................................................................9 
1. 
INTRODUCTION ......................................................................................................12 
2. 
STUDY OBJECTIVE .................................................................................................12 
3. 
STUDY DESIGN .......................................................................................................12 
3.1. 
Overview .....................................................................................................................12 
3.2. 
Sample Size ................................................................................................................12 
3.3. 
Randomization and Treatment Assignment ................................................................13 
3.4. 
Study Periods ..............................................................................................................13 
4. 
STUDY ENDPOINTS ................................................................................................14 
4.1. 
Primary Endpoint ........................................................................................................14 
4.2. 
Secondary Endpoints ..................................................................................................14 
4.3. 
Exploratory Endpoints ................................................................................................15 
4.4. 
Safety Assessments .....................................................................................................15 
4.5. 
Exploratory Biomarker Endpoints ..............................................................................15 
5. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................16 
5.1. 
General Conventions ..................................................................................................16 
5.1.1. 
Analysis of Categorical Endpoints .............................................................................16 
5.1.2. 
Analysis of Continuous Endpoints .............................................................................16 
5.1.3. 
Analysis of Time-to-Event Endpoints ........................................................................16 
5.1.4. 
Analysis of Spirometry Data ......................................................................................16 
5.1.5. 
Analysis of HRCT Data ..............................................................................................17 
5.2. 
Analysis Sets ...............................................................................................................17 
5.2.1. 
Intent-to-Treat Population (ITT) .................................................................................17 
5.2.2. 
Per-Protocol Set (PPS) ................................................................................................17 
5.2.3. 
Safety Analysis Set (SAF) ..........................................................................................17 


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5.2.4. 
Immunogenicity Analysis Set (IGS) ...........................................................................17 
5.3. 
General Data Handling Rules and Presentation Specifications ..................................17 
5.3.1. 
Analysis Period ...........................................................................................................17 
5.3.1.1. 
On-Study Period .........................................................................................................17 
5.3.1.2. 
On-Treatment Period ..................................................................................................18 
5.3.2. 
Baseline Definitions ....................................................................................................18 
5.3.3. 
Formulas .....................................................................................................................18 
5.3.4. 
General Instructions of TLF .......................................................................................18 
5.3.5. 
Handling of Dropouts or Missing Data ......................................................................19 
5.4. 
Interim Analyses and Data Monitoring Committee ....................................................19 
5.5. 
Analysis Visit Window ...............................................................................................19 
6. 
STATISTICAL ANALYSIS ......................................................................................20 
6.1. 
Subject Enrollment and Disposition ...........................................................................20 
6.1.1. 
Eligibility Criteria .......................................................................................................20 
6.1.2. 
Subject Accountability and Disposition .....................................................................20 
6.2. 
Important Protocol Deviations ....................................................................................20 
6.3. 
Demographics and Baseline Characteristics ...............................................................21 
6.3.1. 
Demographics and Baseline Characteristics ...............................................................21 
6.3.2. 
Medical History ..........................................................................................................21 
6.4. 
Prior and Concomitant Medications ...........................................................................21 
6.5. 
Prior and Concomitant Procedures and Non-drug Therapies .....................................22 
6.6. 
Study Drug Exposure and Treatment Compliance .....................................................22 
6.6.1. 
Study Drug Exposure ..................................................................................................22 
6.6.2. 
Treatment Compliance ................................................................................................23 
6.7. 
Efficacy Analysis ........................................................................................................23 
6.7.1. 
Primary Endpoint Analysis and Estimand ..................................................................24 
6.7.1.1. 
Primary Analysis with MMRM ..................................................................................24 
6.7.1.2. 
Sensitivity Analysis ....................................................................................................26 
6.7.1.3. 
Supplemental Analysis ...............................................................................................27 
6.7.1.4. 
Subgroup Analysis ......................................................................................................27 
6.7.2. 
Secondary and Exploratory Endpoints Analysis and Estimands ................................27 


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6.7.2.1. 
Time-to-Event Endpoints ............................................................................................27 
6.7.2.2. 
Continuous Endpoints with MMRM Model ...............................................................29 
6.7.2.3. 
Subgroup Analysis for Secondary Efficacy Endpoints ..............................................31 
6.8. 
Safety Analysis ...........................................................................................................31 
6.8.1. 
Adverse Events (AEs) .................................................................................................31 
6.8.2. 
Special Safety Events .................................................................................................32 
6.8.3. 
Clinical Laboratory Parameters ..................................................................................32 
6.8.4. 
Liver Function Tests ...................................................................................................33 
6.8.5. 
Vital Signs ..................................................................................................................33 
6.8.6. 
Electrocardiogram (ECG) ...........................................................................................34 
6.8.7. 
Physical Examination (PE) .........................................................................................34 
6.8.8. 
Pregnancy Test ............................................................................................................34 
6.9. 
Biomarker Endpoint Analysis .....................................................................................34 
6.10. 
Immunogenicity Analysis and PK ..............................................................................34 
6.10.1. 
Terms and Definitions ................................................................................................35 
6.10.1.1. 
Sample ADA Status ....................................................................................................35 
6.10.1.2. 
Subject ADA Status ....................................................................................................35 
6.10.2. 
Statistical Analysis for Characterization of ADA Immune Response ........................35 
6.10.2.1. 
Incidence of ADA .......................................................................................................35 
6.10.2.2. 
ADA Titer Kinetics .....................................................................................................36 
6.10.3. 
Clinical Implication of ADA Immune Response ........................................................36 
6.10.3.1. 
PK ...............................................................................................................................36 
6.10.3.2. 
Safety and Efficacy .....................................................................................................37 
7. 
CHANGES FROM PROTOCOL ...............................................................................37 
8. 
REFERENCE .............................................................................................................37 
APPENDIX 1. HANDLING MISSING/INCOMPLETE DATES .............................................39 
Appendix 1.1 Missing/Incomplete AE Onset Date .....................................................................39 
Appendix 1.2. Missing/Incomplete AE Stop Date ......................................................................39 
Appendix 1.3. Missing/Incomplete Prior or Concomitant Medication Start Date ......................40 
Appendix 1.4. Missing/Incomplete Prior or Concomitant Medication Stop Date ......................40 
Appendix 1.5. Missing Date Imputation for Last Dose Date ......................................................40 


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APPENDIX 2. ANALYSIS VISIT WINDOWS ........................................................................41 
APPENDIX 3. SGRQ .................................................................................................................45 
APPENDIX 4. UCSD-SOBQ .....................................................................................................50 
APPENDIX 5. LCQ ....................................................................................................................51 
APPENDIX 6. GAP SCORE AND STAGE ...............................................................................52 
APPENDIX 7. EXAMPLE SAS CODE .....................................................................................53 
Appendix 7.1. MMRM ..................................................................................................................53 
Appendix 7.2. Jump-to-Control .....................................................................................................53 
Appendix 7.3. Delta-Adjusting (Tipping Point) Analysis .............................................................54 
Appendix 7.4. Ranked ANCOVA .................................................................................................55 
APPENDIX 8. CHINA CDE REQUIREMENT .........................................................................56 
 
LIST OF TABLES 
Table 1: 
Criteria for Major Protocol Deviations .......................................................................21 
Table 2: 
Classification of Prior and Concomitant Medications ................................................22 
Table 3: 
Fixed Sequence Testing Order of Primary and Secondary Endpoints .......................24 
Table 4: 
Laboratory Tests .........................................................................................................33 
Table 5: 
Criteria for Potentially Clinically Significant Vital Signs ..........................................34 
Table 6: 
Analysis Visit Window for Vital Signs ......................................................................41 
Table 7: 
Analysis Visit Window for PFT .................................................................................42 
Table 8: 
Analysis Visit Window for HRCT .............................................................................42 
Table 9: 
Analysis Visit Window for Labs ................................................................................42 
Table 10: Analysis Visit Window for SGRQ, UCSD-SOBQ, LCQ, PE, and Weight................43 
Table 11: Analysis Visit Window for ECG ................................................................................43 
Table 12: Analysis Visit Window for Biomarkers (Serum and Plasma) ....................................43 
Table 13: Analysis Visit Window for CTGF and ADA (Plasma) ..............................................44 
Table 14: Analysis Visit Window for Pharmacokinetic Concentration (Plasma) ......................44 
 


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LIST OF FIGURES 
Figure 1: 
Study Schema .............................................................................................................13 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Explanation 
ADA 
Anti-Drug Antibody 
AE  
Adverse Event  
ALP  
Alkaline Phosphatase  
ALT 
Alanine Aminotransferase 
ANC 
Absolute Neutrophil Count 
ANCOVA  
Analysis of Covariance  
ANOVA  
Analysis of Variance  
aPTT/PTT 
Activated Partial Thromboplastin Time 
AST  
Aspartate Aminotransferase 
ATC  
Anatomical Therapeutic Class  
ATS 
American Thoracic Society  
BMI 
Body Mass Index 
BTR 
Best-Test Review 
BUN 
Blood Urea Nitrogen 
CCL18 
Chemokine (C-C Motif) Ligand 18 
CDE 
Center for Drug Evaluation 
CI 
Confidence Interval 
CRF 
Case Report Form 
CRP 
C-Reactive Protein  
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTGF 
Connective Tissue Growth Factor 
DBL 
Database Lock 
DLCO 
Diffusion capacity of the Lungs for Carbon Monoxide 
DMC 
Data Monitoring Committee 
ECG  
Electrocardiogram 
EDC 
Electronic Data Capture 
EOS 
End of Study 
EOT 
End of Treatment 
ERS 
European Respiratory Society 
FVC 
Forced Vital Capacity 
FVCpp 
Forced Vital Capacity percentage predicted 
GAP 
GAP index and staging system for IPF: gender (G), age (A), and two 
pulmonary physiological parameters (P) - percentage predicted FVC [%], and 
percentage predicted DLCO [%] 
GGT 
Gamma-Glutamyltransferase 
HAHA 
Human Anti-Pamrevlumab Antibody 
HRCT 
High-Resolution Computed Tomography 
ICF 
Informed Consent Form 
ICH E9 
International Conference on Harmonization Statistical Principles for Clinical 
Trials 
IGS 
Immunogenicity Analysis Set 


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Abbreviation 
Explanation 
IL-6 
Interleukin-6 
IL-8 
Interleukin-8 
INR 
International Normalised Ratio 
IP 
Investigational Product 
IPD 
Important Protocol Deviations 
IPF 
Idiopathic Pulmonary Fibrosis 
IRT 
Interactive Response System 
ITT 
Intent-To-Treat 
IV 
Intravenous 
KL-6 
Krebs von den Lungen 6 
L 
Liter 
LCQ 
Leicester Cough Questionnaire 
LSMean(s) 
Least-Square Mean(s) 
MAR 
Missing At Random 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
mL 
milliliter 
MMP7 
Matrix MetalloProteinase-7 
MMRM 
Mixed Model for Repeated Measures 
NMPA 
China's National Medical Products Administration 
MNAR 
Missing Not at Random 
OLE 
Open Label Extension 
OS 
Overall Survival 
PCS 
Potentially Clinically Significant 
PE 
Physical Examination 
PFT 
Pulmonary Function Test 
PIIINP 
Type III collagen 
PINP 
Procollagen type I N-terminal Propeptide 
PK 
Pharmacokinetic 
PopPK 
Population Pharmacokinetic 
PPS 
Per-Protocol Set 
PROs 
Patient Reported Outcomes 
PT 
Prefer Term 
Q3W 
Every 3 Weeks 
QLF 
Quantitative Lung Fibrosis 
RBC 
Red Blood Cell, or Erythrocyte 
RCM 
Random Coefficient Model 
SAE 
Serious Adverse Event 
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SE 
Standard Error 


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Abbreviation 
Explanation 
SGRQ 
St. George’s Respiratory Questionnaire 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
TGF-beta 
Transforming Growth Factor beta 
TLC 
Total Lung Capacity Volume  
TLF 
Table, Listing, and Figure 
TNF 
Tumor Necrosis Factor 
UCSD-SOBQ 
University of California San Diego – Shortness of Breath Questionnaire 
ULN 
Upper Limit of Normal, value provided by the laboratory 
VEGF 
Vascular Endothelial Growth Factor 
WHODD 
World Health Organization Drug Dictionary 
WOCBP 
Women Of Childbearing Potential 


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1. 
INTRODUCTION 
This statistical analysis plan (SAP) is for the pre-specified reporting of study results for protocol 
FGCL-3019-095, amendment 2.0. Specifications of tables, data listings, and figures (TLF) are 
contained in a separate document. The statistical analyses and summary tabulations described in 
this SAP will provide the basis for the results section of the clinical study report (CSR). The SAP 
will be finalized prior to unblinding after the study Database Lock (DBL). Any major 
modification to this SAP after the signoff will be documented in an SAP amendment or CSR. 
This SAP describes the planned statistical analyses for the double-blind period of the study. 
Statistical analyses for the main study cohort of subjects are planned for inclusion in the body of 
the CSR. 
The open-label extension period (OLE) of the study will have a separate SAP. Additionally, a 
population pharmacokinetic (PopPK) analysis as well as an exposure-response analysis will be 
defined in a separate pharmacokinetic (PK) analysis plan. 
Based on regional regulatory filing needs, region-specific subset analyses may be performed 
following the methodology outlined in this SAP. Refer to Appendix 7 if regulatory submission in 
China is pursued. 
2. 
STUDY OBJECTIVE 
The overall objective of this trial is to evaluate the efficacy and safety of 30 mg/kg intravenous 
(IV) infusions of pamrevlumab as compared to placebo in subjects with Idiopathic Pulmonary 
Fibrosis (IPF). 
3. 
STUDY DESIGN 
3.1. 
Overview 
This is a Phase 3, randomized, double-blind, placebo-controlled multi-center trial to evaluate the 
efficacy and safety of pamrevlumab in subjects with IPF. Approximately 340 subjects will be 
enrolled in this trial. 
3.2. 
Sample Size 
A sample size of 340 subjects will have at least 90% power, based on a two-sided alpha level of 
0.05 for a two-sample t-test, to detect a treatment difference of 120 mL in the primary efficacy 
endpoint, change from baseline in forced vital capacity (FVC, in Liter: L), assuming a common 
standard deviation of 300 mL (allowing about 20% dropout rate). 
The rationale for these sample size assumptions is as follows. In the phase 2 study FGCL-3019-
067, a treatment difference of 178 mL was observed in change from baseline in FVC to 
Week 48. For this study, a conservative treatment difference of 120 mL is assumed. The standard 
deviation is estimated based on published results from other IPF studies. 


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3.3. 
Randomization and Treatment Assignment 
Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms as follows: 
• Arm A: pamrevlumab, 30 mg/kg IV, Q3W (every 3 weeks) 
• Arm B: matching placebo IV, Q3W 
Randomization is stratified by GAP stage (I, II, III) derived from the GAP score obtained at 
screening (Refer to Appendix 6). Calculation of the GAP score for randomization is based on the 
Best-Test Review (BTR) assessment provided by the independent central spirometry vendor 
reader. 
3.4. 
Study Periods 
This study consists of the following study periods (Figure 1): 
• Main (double-blind, placebo-controlled) study period: 
− Screening period: Up to 6 weeks 
− Treatment period: 48 weeks 
• Optional, open label extension (OLE) period: 
Access to pamrevlumab during the OLE period will be available until the last enrolled subject 
completes 48 weeks of treatment in the OLE period, or pamrevlumab is commercially available 
for the indication of IPF, or the Sponsor decides to end the OLE period, whichever occurs first. 
• Follow-up period/final safety assessment: 
− 28 days after the last dose: scheduled visit 
− 60 days after the last dose: follow-up phone call, for a final safety assessment 
Figure 1: 
Study Schema 
 
 
The intent for this study is to evaluate the efficacy and safety profile of pamrevlumab as 
monotherapy in subjects with IPF who were previously treated with an approved therapy but 


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who discontinued that therapy (possible reasons for discontinuation of approved therapy could 
include, but are not limited to, intolerance or disease progression), unless neither treatment is 
available in the host country.  
After randomization and during the treatment period, co-administration of an approved IPF 
therapy (i.e., pirfenidone or nintedanib) is permitted if clinically indicated in the Investigator’s 
opinion, provided that the Investigator assesses the potential risks/benefits of combining 
approved IPF therapies with blinded study treatment. 
Subjects who complete the Week 48 visit of the main study (regardless of the number of study 
drug infusions received and or treatment group assigned in the double-blind period) will be 
eligible to participate in the optional OLE period of the study that offers continuing access to 
pamrevlumab regardless of randomization assignment in the main study. 
Subjects who discontinue study treatment for any reason are encouraged to remain in the study 
and be followed for all study visits and assessments. 
The following assessments will be assessed centrally by independent external vendors or study 
committees: 
• Pulmonary function tests (PFTs) 
• High-resolution computed tomography (HRCT) 
• Acute IPF exacerbations and respiratory hospitalizations 
In addition, an independent Data Monitoring Committee (DMC) will review safety data and 
other clinical data (with the authority to unblind such data) on a periodic basis to monitor overall 
subject safety. 
4. 
STUDY ENDPOINTS 
4.1. 
Primary Endpoint 
• Change in Forced Vital Capacity (FVC) from baseline at Week 48 
4.2. 
Secondary Endpoints 
• Time to disease progression, defined as absolute Forced Vital Capacity percentage 
predicted (FVCpp) decline of ≥10% or death, whichever occurs first 
• Time to the first occurrence of any component of clinical composite endpoint: acute 
IPF exacerbation, respiratory hospitalization, or death, whichever occurs first 
• Change in Quantitative Lung Fibrosis (QLF) volume from baseline at Week 48 
• Time to first acute IPF exacerbation during study 
• Time to all-cause mortality during study 
• Time to first respiratory hospitalization during study 


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4.3. 
Exploratory Endpoints 
• Time to composite of: respiratory hospitalization, absolute FVCpp decline ≥10%, or 
all-cause death, whichever occurs first 
• Change in absolute FVCpp from baseline at Week 48 
• Change in relative FVCpp from baseline at Week 48 
• Change in St. George’s Respiratory Questionnaire (SGRQ) score from baseline at 
Week 48 
• Change in University of California San Diego – Shortness of Breath Questionnaire 
(UCSD-SOBQ) score from baseline at Week 48 
• Change in Leicester Cough Questionnaire (LCQ) from baseline at Week 48 
4.4. 
Safety Assessments 
• Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse 
events (TESAEs) 
• Clinical laboratory parameters  
• Vital signs 
• Immunogenicity (Human Anti-Human Antibody [HAHA] formation, also named 
ADA: anti-drug antibody) 
• Hypersensitivity/anaphylactic reactions 
4.5. 
Exploratory Biomarker Endpoints 
Biomarkers to be analyzed may include but are not limited to: 
• Connective Tissue Growth Factor (CTGF) 
• markers of inflammation such as C-reactive protein (CRP), tumor necrosis factor 
(TNF), interleukin-6 (IL-6), interleukin-8 (IL-8), and chemokine (C-C motif) ligand 
18 (CCL18) 
• markers of fibrosis and collagen synthesis such as transforming growth factor beta 
(TGF-beta), procollagen type I N-terminal propeptide (PINP), and type III collagen 
(PIIINP) 
• other markers of tissue remodeling and angiogenesis such as angiopoietins, vascular 
endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP7), and Krebs 
von den Lungen 6 (KL-6). 
 


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5. 
GENERAL STATISTICAL CONSIDERATIONS 
5.1. 
General Conventions 
All data collected will be included in the data listings. All analyses will be performed using 
SAS® Version 9.3 or higher. 
5.1.1. 
Analysis of Categorical Endpoints 
Frequency distributions (number and percentage of subjects) will be presented for categorical 
variables. 
5.1.2. 
Analysis of Continuous Endpoints 
For continuous variables, descriptive statistics, including n, mean, standard deviation (SD), 
median, minimum, and maximum, will be presented.  
Line graphs of group mean (and standard error: SE) and mean change from baseline (and SE) 
values will be plotted over visits as appropriate. Additional plots such as Least-square mean (SE) 
or boxplot will be provided as appropriate. 
5.1.3. 
Analysis of Time-to-Event Endpoints 
Kaplan-Meier curves for time-to-event endpoints will be plotted as appropriate. Comparisons of 
the respiratory hospitalization and acute IPF exacerbation endpoints will be based on the events 
identified by the Independent Adjudication Committee in accordance with the Adjudication 
Charter. 
5.1.4. 
Analysis of Spirometry Data 
All spirometry results are reviewed by the independent spirometry Over-Reader group for 
quality, during their Best Test Review (BTR). The Over-Reader does an overall quality rating of 
the spirometry data (“acceptable”, “borderline acceptable” or “unacceptable”) and determines 
which is the “Best” FVC (L) value and corresponding FVCpp for each test. 
For each visit, only one FVC value and corresponding FVCpp that is identified by the Over-
Reader as the “Best” FVC value, with an overall quality rating of “acceptable” or “borderline 
acceptable” will be used for analyses. 
NOTE: A BTR is performed for each spirometry.  In the situation where at a visit multiple 
spirometries were performed, the result considered for the analyses will be selected as follows: 
Definition of “Best” post-BTR FVC value (and correlated FVCpp value): The “Best” value will 
be defined as that which meets the following criteria: (1) FVC value was selected after BTR by 
over-reader as the best test result; and (2) Result received an acceptable or borderline acceptable 
BTR rating. 
• For the Day 1 assessment (Baseline), the “Best” post-BTR FVC value (and correlated 
FVCpp value) as defined above which also meets the following criteria will be used: 
(1) PFT was performed on or prior to Day 1; and (2) Result met eligibility criteria, 


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that is, correlated FVCpp value was within the range of >45% and <95%. The 
qualifying Day 1 value will be used whenever a qualifying Day 1 value is available; 
otherwise, the qualifying value on the last visit prior to Day 1 will be used. In cases 
where there is more than one set of PFTs performed on the same day, the highest of 
the multiple qualifying values will be used. 
• For all subsequent (post-Day 1) visits, the “Best” post-BTR FVC value (and 
correlated FVCpp value) as defined above which correlates with the study visit will 
be used for FVC and FVCpp analyses. 
5.1.5. 
Analysis of HRCT Data 
HRCT images that meet the quality control standards as assessed by the independent radiology 
imaging group will be considered for the analyses. 
5.2. 
Analysis Sets 
5.2.1. 
Intent-to-Treat Population (ITT) 
The intent-to-treat population includes all randomized subjects. Subjects will be analyzed 
according to their randomized treatment arm regardless of the actual study treatment received. 
5.2.2. 
Per-Protocol Set (PPS) 
The per-protocol set is defined as all randomized subjects who have completed at least 36 weeks 
of treatment, with baseline and at least one post-baseline PFT assessment, and no major protocol 
deviation(s) that significantly impact efficacy analyses. 
5.2.3. 
Safety Analysis Set (SAF) 
The safety analysis set includes all subjects who have received any study drug. Subjects will be 
analyzed according to the treatment actually received. 
5.2.4. 
Immunogenicity Analysis Set (IGS) 
The IGS will include all subjects who are in the SAF and have a baseline evaluable 
immunogenicity assessment and at least 1 post-baseline evaluable (i.e., positive, negative) 
immunogenicity assessment. 
5.3. 
General Data Handling Rules and Presentation Specifications 
5.3.1. 
Analysis Period 
5.3.1.1. 
On-Study Period 
Unless otherwise specified, the efficacy analysis will be based on the on-study period, which 
includes all data collected during the double-blind period. 
For the safety analysis, all safety assessments beyond 60 days of the last dose will be excluded 
from summary tables or figures. 


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5.3.1.2. 
On-Treatment Period 
The on-treatment analysis includes only the assessments that are observed during on-study 
period as defined above (Section 5.3.1.1), but within 3 weeks after the last study drug infusion in 
the double-blind period. 
5.3.2. 
Baseline Definitions 
Baseline for PFTs is defined as the last “Best” PFT (from the Over-Reader) before the first study 
drug infusion (or randomization date if no infusion is received) (Section 5.1.4). 
Baseline for all other endpoints is defined as the last measurement prior to the first study drug 
infusion (or randomization date if no infusion is received). Unscheduled visits will be considered 
for baseline. 
5.3.3. 
Formulas 
• Study Day Calculation 
− The day when a subject receives the first dose of study drug after randomization is 
designated as Day 1. For subjects who have not received any study drug in an ITT 
analysis, their randomization date will be used as Day 1. 
− Study day of an assessment/procedure is calculated as follows. 
 For assessments or procedures on Day 1 or later: 
Study day = assessment/procedure date – Day 1 date + 1 
 For assessments or procedures earlier than Day 1: 
Study day = assessment/procedure date – Day 1 date 
• Body Mass Index (BMI) =
𝑊𝑊𝑊𝑊𝑊𝑊𝑊𝑊ℎ𝑡𝑡 (𝑘𝑘𝑘𝑘)
𝐻𝐻𝐻𝐻𝐻𝐻𝐻𝐻ℎ𝑡𝑡 (𝑐𝑐𝑐𝑐)2 
• Body weight, height, and temperature will be converted using the following formula: 
− kg = lb/2.2 
− cm = 2.54 × in 
− 
oC = (5/9) × (oF – 32) 
• Absolute Change from Baseline = Value at Post-baseline visit – baseline value 
• Relative change from baseline (%) is derived with the formula below: 
𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 𝑎𝑎𝑎𝑎 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣−𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣
𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣
× 100 
5.3.4. 
General Instructions of TLF 
• For continuous variables that are recorded as “<X” or “>X”, the value of “X” will be 
used in the calculation of summary statistics. 


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• All reporting values (mean, median, SD, SE, LSMean, 95% CI, etc.) for the 
continuous variables will have 1 additional decimal place than raw data. Min and 
Max will have the same decimal place as raw data. 
• All percentages will be rounded to one decimal place. The percentage will be 
suppressed when the count is zero. All durations of time will have 1 decimal place. 
• All tables and listings will have a header showing “FibroGen, Inc.”, the protocol 
number (ZEPHYRUS 2), date of data cutoff, and Page x of y. A footer will show the 
program file path/name, output file path/name, date of data extraction, run date, and 
run time. 
5.3.5. 
Handling of Dropouts or Missing Data 
All assessments collected will be considered for analyses regardless of whether such data were 
collected during treatment or after a subject discontinued treatment. All analyses assume the 
missing data are missing at random (MAR), unless stated otherwise. Detailed missing data 
handling is described in the analysis of specific endpoints. 
5.4. 
Interim Analyses and Data Monitoring Committee 
In addition to routine safety monitoring, an independent DMC will be established to review 
safety data on an ongoing basis. A DMC charter will establish the procedures, meeting 
frequency, and scope of responsibilities of the committee. 
This study has no planned or pre-specified interim analysis for either efficacy or futility. 
5.5. 
Analysis Visit Window 
Analysis visits, instead of the nominal visits from case report form (CRF), derived from visit 
dates and visit time windows will be used in the by-visit analyses. Unscheduled visits within a 
visit window (defined in Appendix 2) will be grouped into the closest scheduled visits based on 
the visit date. For subjects who have more than one measurement at a certain analysis visit, the 
last measurement will be used, with the following exceptions: 
• Liver function tests, such as Alanine Aminotransferase (ALT), Aspartate 
Aminotransferase (AST), Gamma-Glutamyltransferase (GGT), Alkaline Phosphatase 
(ALP), and total bilirubin, in which the maximum value will be used. 
• Spirometry data: the best value to be used for analysis as defined in Section 5.1.4. 
• Vital signs: the values on the infusion days will be used if applicable. 
• ADA assessment: select in the order of 1) last ADA+ assessment; 2) earlier ADA+ 
assessment; 3) last ADA- assessment. 


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6. 
STATISTICAL ANALYSIS 
6.1. 
Subject Enrollment and Disposition 
6.1.1. 
Eligibility Criteria 
Eligibility criteria will be summarized for all screened subjects. The data will be summarized 
with respect to: 
• number of subjects screened 
• number (%) of subjects screen-failed 
• number (%) of subjects for each failed inclusion/exclusion criterion 
6.1.2. 
Subject Accountability and Disposition 
Subject level inclusion criteria not met/exclusion criteria met listings will be provided. 
The number (%) of subjects randomized (ITT), dosed (SAF), per-protocol set (PPS), 
Immunogenicity Analysis Set (IGS), completed the main study, entered the OLE period, and 
discontinued prematurely from treatment and study will be presented for each treatment group 
and all subjects pooled. 
Reasons for premature discontinuation will be summarized by treatment group for the ITT 
population. 
In addition, discrepancies between the randomization stratification factor derived from data in 
the Electronic Data Capture System (EDC) vs. data from the Interactive Response System (IRT) 
randomization system will be summarized. A listing will show any discrepancies between the 
two systems. If more than 5% discrepancies were identified, EDC randomization stratification 
factor will be used as fixed effects in the statistical analysis if applicable; otherwise, IRT 
randomization stratification factor will be used, unless otherwise specified. 
6.2. 
Important Protocol Deviations 
The number and percentage of subjects with important protocol deviations will be categorized 
and tabulated as appropriate for the ITT population. COVID-19-related important protocol 
deviations will be summarized in a separate table. All protocol deviations will be finalized prior 
to unblinding. 
A subset of pre-specified major protocol deviations will exclude some patients in the PPS 
analyses if these deviations significantly impact efficacy analyses. These major PDs will be 
reviewed and finalized by following FibroGen medical review process prior to database lock and 
unblinding. Considerations will be given according to the following table. 


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Table 1: 
Criteria for Major Protocol Deviations 
Number 
Major Protocol Deviation 
1 
Violation of any inclusion or exclusion criteria that may affect the assessment of 
efficacy or safety of the study drug*  
2 
Withdrawal Deviation: Subject met withdrawal criteria during the study but was 
not withdrawn* 
3 
Dosing Deviation: Subject received the wrong treatment or incorrect dose, 
including incorrect timing of a dose, which may affect the assessment of efficacy 
or safety of the study drug* 
4 
Administration of prohibited concomitant medication that may impact evaluation 
of efficacy of the study drug* 
5 
Significant noncompliance with study procedures that may impact evaluation of 
efficacy of the study drug will be evaluated case by case* 
* Major PDs will be reviewed and finalized by following FibroGen medical review process; these five categories 
may not cover all IPDs. 
6.3. 
Demographics and Baseline Characteristics 
6.3.1. 
Demographics and Baseline Characteristics 
Demographics and important baseline characteristics will be summarized for the ITT by 
treatment arm and all pooled. These may include but are not limited to age, age group (≤64, 65-
74, ≥75), sex, ethnicity, race group, weight, body mass index (BMI), smoking history, prior 
treatment with an approved IPF therapy (Yes/No), GAP stage (I, II, III), and years since the first 
diagnosis of IPF. Age is defined as the age on the day of signing the informed consent form 
(ICF). Years since the first diagnosis will be derived using the formula: date of ICF- date of IPF 
diagnosis+1. Partial missing date of IPF diagnosis will be imputed as Jan. 01 (if month is 
missing), or 01 (if day is missing). 
Baseline values for efficacy assessments will be presented in baseline tables as appropriate. 
Comparability of baseline characteristics between treatment groups will be assessed using 
analysis of variance (ANOVA) model for continuous variables and Chi-squared test for 
categorical variables. The nominal p-values will be presented for reference only. 
6.3.2. 
Medical History 
Medical History coded by Medical Dictionary for Regulatory Activities (MedDRA, Version 25.0 
or higher) will be summarized for the ITT Population. 
6.4. 
Prior and Concomitant Medications 
The latest World Health Organization Drug Dictionary (WHODD Global B3 Mar2022, or higher 
version) will be used to classify prior and concomitant medications by therapeutic class and 
preferred term. 
Prior medication is defined as any medication taken and stopped prior to the first dose of the 
study drug. Concomitant medication is defined as any medication taken after the first dose of the 


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study drug and before the last dose days +60 days. For subjects who are treated in the OLE, 
medications that started after 1st dose in the OLE period may be considered as concomitant 
medication for the OLE period, but not for the double-blind period. Partially or incompletely 
missing prior/concomitant medication start or stop dates will be imputed (Appendix 1). Table 2 
provides the classification guideline when medication starting or ending dates are missing. 
Table 2: 
Classification of Prior and Concomitant Medications 
End Date 
Start Date 
Before start of study 
drug administration 
On or after start of study 
drug administration 
Missing 
Before start of study drug 
administration 
Prior 
Concomitant 
Concomitant 
On or after start of study drug 
administration and before the last 
dose date +60 days 
- 
Concomitant 
Concomitant 
Missing 
Prior 
Concomitant 
Concomitant 
Both prior and concomitant medication usage will be summarized by the number (%) of subjects 
receiving the drug within each therapeutic class and ATC code level 3 and preferred term for the 
SAF. Multiple usages of the same drug by a patient will be counted only once. 
Separate summaries may be provided for prior and concomitant medications of special interest 
such as the approved IPF medications (pirfenidone and/or nintedanib). 
To evaluate the use of co-administered medications that are narrow therapeutic CYP substrates, 
the concomitant medication for narrow therapeutic index cytochrome P450 substrates will be 
listed and summarized. The list of related medications will be finalized prior to database lock. 
6.5. 
Prior and Concomitant Procedures and Non-drug Therapies 
Procedures and non-drug therapies were coded with MedDRA Version 25.0 or higher version. 
Prior/Concomitant procedures and non-drug therapies will be defined and summarized similarly 
to prior and concomitant medications (Details in Section 6.4). Partially or incompletely missing 
procedures and non-drug therapies start or stop dates will be imputed similarly to 
prior/concomitant medications (Appendix 1). 
6.6. 
Study Drug Exposure and Treatment Compliance 
6.6.1. 
Study Drug Exposure 
Exposure to the study drug will be summarized in terms of treatment duration for the SAF. 
Duration of study treatment in weeks is calculated as: (last dose date – first dose date + 1)/7. 
Duration of study treatment will be summarized as a continuous variable and be tabulated by the 
categories as follows: 
• <6 weeks 
• 6 to <12 weeks 
• 12 to <18 weeks 


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• 18 to <24 weeks 
• 24 to <36 weeks 
• ≥36 weeks 
Number (%) of subjects by the total number of infusions (1-3, 4-6, 7-9, 10-12, ≥13) received, 
overall average infusion doses (in mg/kg), whether infusion was missed/interrupted and reason 
for missed/interruption, and patient-exposure years (PEY) will be summarized for the SAF. 
6.6.2. 
Treatment Compliance 
The compliance will be presented as % of the actual dose administered out of the total planned 
dose of infusions by end of study (EOS) or by discontinuation in subjects who discontinued. 
𝐶𝐶𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜 (%) =
𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 𝑤𝑤ℎ𝑖𝑖𝑖𝑖𝑖𝑖 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑖𝑖𝑖𝑖 𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡𝑡× 100 
Descriptive statistics for study drug compliance will be presented by treatment group for the 
SAF. Treatment compliance will be summarized as a continuous variable and as a categorical 
variable (<70%, 70% –<80%, 80% –<90%, 90%-110%, and >110%). 
6.7. 
Efficacy Analysis 
The primary and secondary endpoints will be tested using a fixed sequence analysis approach to 
preserve the study-wide error rate of 5%. Under the sequential analysis, the primary and 
secondary efficacy endpoints will be tested in a defined sequence according to the order listed in 
Table 3 each at the usual alpha= 0.05 level of statistical significance. The testing will cease when a 
failure occurs in the pre-determined sequential hypothesis testing and all p-values for the subsequent 
testing will be considered nominal. All p-values for exploratory endpoints will be considered 
nominal. 
All analyses for efficacy endpoints will be performed for the ITT population during the On-
Study period (Section 5.3.1.1), unless noted otherwise. The placebo group will be used as the 
reference group for all treatment comparisons. 


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Table 3: 
Fixed Sequence Testing Order of Primary and Secondary Endpoints 
Testing 
order 
Endpoints 
1 
Change in FVC (L) from baseline at Week 48 (Primary Endpoint) 
2 
Time to disease progression, defined as absolute FVCpp decline of ≥10%  
or death, whichever occurs first 
3 
Time to the occurrence of any component of the clinical composite endpoint: 
acute IPF exacerbation, respiratory hospitalization, or death (whichever occurs 
first) 
4 
Change in QLF volume from baseline at Week 48 
5 
Time to first acute IPF exacerbation during study 
6 
Time to all-cause mortality during study 
7 
Time to first respiratory hospitalizations during study  
6.7.1. 
Primary Endpoint Analysis and Estimand 
The primary endpoint is change from baseline in FVC (L) at Week 48. 
The hypotheses to be tested for the primary efficacy analysis is: 
H0: Change from baseline in FVC (L) at week 48 for the pamrevlumab arm = Change from 
baseline in FVC (L) at week 48 for the placebo arm 
Versus: 
H1: Change from baseline in FVC (L) at week 48 for the pamrevlumab arm ≠ Change from 
baseline in FVC (L) at week 48 for the placebo arm 
6.7.1.1. 
Primary Analysis with MMRM 
6.7.1.1.1. Estimand Strategy 
The primary estimand is intended to provide a population level estimate of the treatment effect of 
the pamrevlumab on a continuous endpoint, regardless of participant compliance with the IP 
(investigational product) dosing. 
6.7.1.1.2. Population of Interest 
The ITT population includes all randomized subjects during the on-study period as defined in 
Section 5.3.1.1. Male and female patients aged 40 or above with IPF diagnosis under American 
Thoracic Society/European Respiratory Society (ATS/ERS) criteria (Raghu 2018), and not 
currently receiving treatment with the 2 approved antifibrotic standard of care medications. 
6.7.1.1.3. Intercurrent Event Handling Strategy 
Treatment discontinuation due to non-death reasons: Treatment policy strategy will be used. 
Missing data are assumed to be missing at random. 


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Death: Post-death FVC values will be set as the worst (lowest) post-baseline FVC values across 
all randomized subjects in the double-blind period. Missing study day will be imputed as the 
target day of each analysis visit. 
6.7.1.1.4. Analysis Variable 
Change from baseline in all FVC assessments in the double-blind period, including scheduled, 
unscheduled, and available assessments after treatment discontinuation, up to week 48 during the 
On-Study period (Section 5.3.1.1), will be included in the analysis. 
In the situation where a subject has more than one record of FVC within an analysis visit, the 
best value will be used for MMRM. 
6.7.1.1.5. Population Summary for Treatment Comparison 
Treatment difference of Least-square mean (LSMean) and SE at week 48 and the corresponding 
95% CI will be presented. 
All post-baseline visits for the specified parameters below during the double-blind period will be 
included in the analysis. Change from baseline for the specified endpoints (excluding baseline 
visits) will be analyzed using a Mixed Model for Repeated Measures (MMRM) approach with 
fixed effects for treatment, visit (as a factor), treatment-by-visit interaction, randomization 
stratification factor, and covariates (baseline values, sex, age, race group, and height). Example 
SAS code in Appendix 7.1. 
The following graphical displays will be provided: 
• The mean (± SE) FVC over time by treatment group 
• The mean (± SE) FVC change from baseline by treatment group 
• The LSmean (± SE) estimated FVC change from baseline over time by treatment 
group (as estimated in the primary analysis) 
6.7.1.1.6. Covariance Structure Strategy 
The unstructured covariance pattern model will be used first. The by-treatment-group option will 
be added to the covariance pattern to improve the model fit as appropriate. If the model using the 
unstructured covariance pattern does not converge, the following covariance structures will be 
tested in sequence: heterogeneous Toeplitz, homogeneous Toeplitz, first-order autoregressive, 
compound symmetry, and variance component, until the model converges. 
If the model doesn’t converge for all six covariance structures listed above, then the following 
attempts will be made: 1) sandwich covariance estimator will be used; 2) some least significant 
factors or interaction terms (p>0.05) can be dropped from the model to achieve convergence. The 
revised model with fewer factors or interaction terms will be tested using the same sequence as 
specified above. 
This covariance structure strategy will apply to all analyses on continuous primary, secondary, 
and exploratory efficacy endpoints if appropriate. 


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6.7.1.2. 
Sensitivity Analysis 
The following sensitivity analysis under the same estimand framework as the primary analysis 
defined in Section 6.7.1 will be performed on FVC: 
6.7.1.2.1. Linear Slope Model (RCM) 
The random coefficient linear regression model (RCM) with a random effect for the slope of 
time will be performed. The time in the RCM model will be calculated as the elapsed weeks 
(continuous) from the first infusion (or randomization if not dosed) to the assessment date. The 
RCM model will also include fixed effects of treatment, time, treatment-by-time interaction, 
randomization stratification factor, baseline FVC volume, and covariates (age, sex, race group, 
and height). Baseline visits will be set as 0 and included in the RCM model. In the situation 
where a subject has more than one record of FVC on different study days within an analysis visit, 
the highest qualifying FVC on each study day (Section 5.1.4) will be used for RCM. 
6.7.1.2.2. Jump-to-Control Analysis 
The goal of the jump-to-control analysis is to address the possibility of data being missing not at 
random (MNAR). The missing data pattern for the pamrevlumab subjects after withdrawal from 
the study can be assumed to switch to the same data pattern as subjects on the placebo treatment. 
Subjects that discontinued from the placebo arm are assumed to have the same data pattern as 
placebo subjects that remain in the study (excluding post-death missing values defined in 
Section 6.7.1.1.3). This is often called the jump-to-control approach.  
The analysis of covariance (ANCOVA) model will contain terms for treatment, baseline FVC 
measurements, covariates (age, sex, race group, and height), and the randomization stratification 
factor (Example SAS code in Appendix 7.2). 
6.7.1.2.3. Delta-Adjusting (Tipping Point) Analysis 
An alternative assumption is that the missing data for the pamrevlumab treated subjects who 
discontinue early have a lower expected value than the pamrevlumab subjects remaining in the 
study, while subjects who discontinue from the placebo arm are assumed to have the same data 
pattern as placebo subjects remaining in the study (excluding post-death missing values defined 
in Section 6.7.1.1.3). This is often called the delta-adjusting (or tipping point) approach 
(Example SAS code in Appendix 7.3). 
ANCOVA will be performed as Section 6.7.1.2.2. 
6.7.1.2.4. Ranked ANCOVA Analysis 
A ranked ANCOVA analysis (a non-parametric analysis) will be performed on the ranked 
change from baseline values in FVC at Week 48. The ranked ANCOVA was the primary 
efficacy endpoint analysis in the pirfenidone phase 3 trials. 
Missing week 48 values will be imputed as the average value from three subjects with the 
smallest sum of squared differences over the visits with non-missing data between each of the 
three subjects and the early terminated subject. 


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Death: Subjects with missing data due to death were ranked worse than those who remained 
alive. Subjects who died were ranked according to the number of days from randomization until 
death, with the shortest time to death as the worst rank. 
The ranked ANCOVA with terms for sex, age, race group (white and non-white), height, 
randomization stratification factor, and standardized rank baseline FVC value as a covariate will 
be performed on the ranked change from baseline in FVC at week 48 (Example SAS code in 
Appendix 7.4). The p-value for treatment comparison will be presented. 
6.7.1.3. 
Supplemental Analysis 
The following supplemental analysis under the same estimand framework as the primary analysis 
defined in Section 6.7.1 will be performed on FVC: 
6.7.1.3.1. On-Treatment Period Analysis 
An additional analysis will be performed for assessments performed during the On-treatment 
period as defined in Section 5.3.1.2. FVC assessments beyond 3 weeks after the last study drug 
infusion will be excluded from the analysis. 
6.7.1.3.2. Per-Protocol Set Analysis 
An additional analysis will be performed for subjects in PPS as defined in Section 5.2.2. Same as 
Section 6.7.1.1.4. EDC randomization stratification factor will be used for analysis in PPS. 
6.7.1.4. 
Subgroup Analysis 
The primary analysis will be repeated for relevant and appropriate subgroups. The LSMean of 
treatment difference and corresponding 95% CI will be presented in a forest plot as appropriate. 
The subgroups may include but are not limited to sex, age group, race group (white vs. others), 
prior use of approved IPF treatments (yes/no), any use of approved IPF treatments during the 
study (yes/no), country/geographic region (Europe/Latin America/US/Asia Pacific), country 
(China/Non-China), GAP stage (I, II, III), and ADA status (Positive, Negative, or unknown; 
details in Section 6.10). 
6.7.2. 
Secondary and Exploratory Endpoints Analysis and Estimands 
The secondary endpoints during the on-study period (as defined in Section 5.3.1.1) will be 
analyzed in the order specified in Table 3. In addition, on-treatment analysis and subgroup 
analysis (both considered nominal) will also be performed for secondary efficacy endpoints. All 
Exploratory endpoint analyses will be considered nominal. 
6.7.2.1. 
Time-to-Event Endpoints 
6.7.2.1.1. Estimand Strategy 
The secondary estimands are intended to provide a population level estimate of the treatment 
effect of the pamrevlumab on time-to-event endpoints; regardless of participant compliance with 
the IP dosing. 


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6.7.2.1.2. Population of Interest 
Same as Section 6.7.1.1.2 
An additional analysis will be performed for all secondary endpoints during the on-treatment 
period as defined in Section 5.3.1.2. 
6.7.2.1.3. Intercurrent Event Handling Strategy 
Treatment discontinuation (such as early termination due to AEs, Lost to Follow-Up, Withdrawal 
by Subject, Physician Decision, Protocol Deviations, etc.): Treatment policy strategy will be 
used. 
Death: Composite strategy will be used if death is a component of the endpoint. 
6.7.2.1.4. Analysis Variables 
6.7.2.1.4.1. Time (Days) to disease progression 
Time (Days) to disease progression is defined as the number of days from randomization to 
either the first occurrence of an absolute ≥10% decline from baseline in FVCpp or all-cause 
death based on observed data, whichever occurs earlier during the on-study period as described 
in Section 5.3.1.1. Subjects who die without any post-baseline PFT assessments will be 
considered as an event on the date of death. 
Subjects without an event will be censored on the date of the last PFT assessment after 
randomization in the double-blind period. Alive/Censored subjects without any post-baseline 
PFT assessments will be censored on Day 1. 
6.7.2.1.4.2. Time (Days) to the first occurrence of any component of the clinical composite 
endpoint: acute IPF exacerbation, respiratory hospitalization, or death 
Time (Days) to the occurrence of any component of the clinical composite endpoint is defined as 
the number of days from randomization to either the first occurrence of acute IPF exacerbation 
(including both confirmed and suspected cases), respiratory hospitalization, or death during the 
on-study period as described in Section 5.3.1.1. 
Subjects without an event will be censored on the date of last known alive during the double-
blind period. 
6.7.2.1.4.3. Time (days) from randomization to first adjudicated acute IPF exacerbation 
Time (Days) to first acute IPF exacerbation is defined as the number of days from randomization 
to either the first occurrence of adjudicated acute IPF exacerbation (including both confirmed 
and suspected cases) as described in Section 5.3.1.1. 
Subjects without an event will be censored on the date of last known alive during the double-
blind period. 


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6.7.2.1.4.4. Time (days) from randomization to all-cause mortality 
Subjects without an event will be censored on the last date known alive in the double-blind 
period. Any survival vital status will be included for early discontinued subjects. 
6.7.2.1.4.5. Time (days) from randomization to first adjudicated respiratory 
hospitalization 
Subjects without an event will be censored on the date of last known alive during the double-
blind period. 
6.7.2.1.4.6. Time (Days) to the first occurrence of composite of adjudicated respiratory 
hospitalization, absolute FVCpp decline ≥10%, or all-cause death 
Time (days) to the first occurrence of composite is defined as from randomization to the first 
occurrence, which includes adjudicated respiratory hospitalization, all-cause death, or absolute 
FVCpp decline ≥10%. Subjects who died without any post-baseline PFT assessments or 
respiratory hospitalization events will be considered as an event on the date of death. 
Subjects without an event will be censored with the same rule defined in Section 6.7.2.1.4.1. 
6.7.2.1.5. Population summary for treatment comparison 
The hazard ratio and its corresponding 95% CI will be presented. P-value from stratified Log-
rank test will also be presented. 
All time-to-event analyses will include data collected in the double-blind period. The stratified 
Cox proportional hazard model including baseline FVCpp stratified by randomization 
stratification factor will be used to estimate the hazard ratio and its corresponding 95% CI. A 
stratified log-rank test stratified by randomization stratification factor will be used for treatment 
comparison. 
For time from randomization to the first acute IPF exacerbation, all events pre-defined in the 
adjudication charter will be adjudicated by an independent Adjudication Committee. The 
adjudicated results will be summarized by categories of confirmed, suspected, or not acute 
respiratory exacerbation. 
In addition, all acute respiratory exacerbations will be further summarized as: 
 
• a triggered acute respiratory exacerbation 
• an idiopathic acute exacerbation (i.e., no trigger identified). 
6.7.2.2. 
Continuous Endpoints with MMRM Model 
6.7.2.2.1. Estimand Strategy 
Same as Section 6.7.1.1.1 
6.7.2.2.2. Population of Interest 
Same as Section 6.7.1.1.2 


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6.7.2.2.3. Intercurrent Event Handling Strategy 
Same as Section 6.7.1.1.3 
For all post-death analysis visits, the missing values will be set as the worst observed post-
baseline values (lowest FVCpp and LCQ score, highest QLF, UCSD-SOBQ, and SGRQ score) 
across all subjects in the double-blind period. Study day will be imputed as the target day of the 
corresponding analysis visit. 
6.7.2.2.4. Analysis Variables 
6.7.2.2.4.1. Change from baseline in QLF volume 
The Quantitative Lung Fibrosis (QLF) volume is calculated as QLF=total lung capacity volume 
(TLC) * % of quantitative lung fibrosis for fibrosis of the whole lung. 
6.7.2.2.4.2. Absolute change from baseline in FVCpp 
The absolute change from baseline in FVCpp is derived with the formula below: 
𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑒𝑒 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣−𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵 
6.7.2.2.4.3. Relative change from baseline in FVCpp 
The relative change (%) from baseline in FVCpp is the change from baseline FVCpp value as a 
percentage of the baseline FVCpp value and is derived with the formula below: 
𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣−𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵
𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵 𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹𝐹 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣
× 100 
6.7.2.2.4.4. Change from baseline in SGRQ 
Refer to Appendix 3 for details of scores for St. George's Respiratory Questionnaire (SGRQ). 
The total score of SGRQ together with the symptom, activity, and impact domain scores, will be 
included in the analysis. 
6.7.2.2.4.5. Change from baseline in the total score of UCSD-SOBQ 
Refer to Appendix 4 for details of scores for University of California, San Diego – Shortness of 
Breath Questionnaire (UCSD-SOBQ). 
6.7.2.2.4.6. Change from baseline in LCQ 
Refer to Appendix 5 for details of scores for Leicester Cough Questionnaire (LCQ). The total 
score of LCQ together with the physical, psychological, and social domains cores, will be 
included in the analysis. 
6.7.2.2.5. Population Summary for Treatment Comparison 
Treatment difference of LSMeans (and SE) at each scheduled visit and the corresponding 95% 
CI will be presented. 


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All post-baseline visits for the specified parameters below during the double-blind period will be 
included in the analysis. Change from baseline for the specified endpoints (excluding baseline 
visits) will be analyzed using a Mixed Model for Repeated Measures (MMRM) approach with 
fixed effects for treatment, visit (as a factor), treatment-by-visit interaction, randomization 
stratification factor, and covariates (baseline values, sex, age, race group, and height). Covariates 
of sex, age, race group, and height will be excluded from the model for FVCpp since these 
variables have already been adjusted in the definition of FVCpp. 
6.7.2.3. 
Subgroup Analysis for Secondary Efficacy Endpoints 
The same subgroup analysis defined in Section 6.7.1.4 will be performed for all secondary 
efficacy endpoints. 
6.8. 
Safety Analysis 
The safety analyses will be performed for the SAF. 
6.8.1. 
Adverse Events (AEs) 
Adverse events will be coded using MedDRA. 
A new or worsening AE occurring on or after the first dose of study drug and within 60 days after 
the last dose of study drug is defined as a treatment-emergent adverse event (TEAE). AEs that 
started after 1st dose in the OLE period will be excluded from the main study. Partially or 
incompletely missing AE start/stop date/time will be imputed (Appendix 1). 
If more than one event occurs with the same system organ class (SOC) and preferred term (PT) 
for the same patient, the patient will be counted only once for that preferred term using the most 
severe and most related occurrence for the summarization by common terminology criteria for 
adverse events (CTCAE) severity grade and relationship to the study treatment. Relationship to 
study treatment will be imputed as “Related” for any TEAE with a missing value for 
relationship. 
The cumulative incidence of the following AE categories including the number (%) of subjects 
will be produced: 
• Summary of all AEs 
• TEAEs by PT 
• TEAEs by SOC and PT 
• TEAEs by SOC, PT, and maximum severity 
• TEAEs by SOC, PT, and investigator-determined relationship 
• TEAEs with severity grade ≥3 by SOC and PT 
• TEAEs related to study treatment determined by the investigator by SOC and PT 
• TEAEs with frequency ≥ 5% of subjects in either treatment arm by SOC and PT 


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• Non-serious TEAEs with frequency ≥ 5% of subjects in either treatment arm by SOC 
and PT (Note: this is required for ClinicalTrials.gov) 
• TEAEs leading to discontinuation of study treatment by SOC and PT 
• TEAEs leading to interruption of study treatment by SOC and PT 
• Treatment-emergent serious AEs (TESAEs) by SOC and PT 
• TESAEs by PT 
• TESAEs by SOC, PT, and maximum severity 
• TESAEs related to study treatment determined by the investigator by SOC and PT 
• Fatal TESAEs (i.e., adverse events that have an outcome of death) by SOC and PT 
• All-cause deaths 
Listings of all adverse events, TESAEs, TEAEs leading to study treatment discontinuation, 
TEAEs leading to death, and all-cause deaths will be provided. 
In addition, TEAEs and TESAEs will be presented by subgroups as described in Section 6.7.1.4 
along with an additional subgroup assessment by concomitant steroid medication use. 
6.8.2. 
Special Safety Events 
Treatment-emergent special safety events including: 
1. Hypersensitivity (any time) 
2. Infusion reactions (occurred on the day or the day after any study drug infusion) 
3. Anaphylactic reactions (occurred on the day or the day after any study drug infusion) 
Items 1 and 2 include both hypersensitivity and angioedema events. Both items 1 and 2 will be 
listed and summarized similarly to TEAEs: 
• Events by event type, SOC, PT, and maximum severity 
• Events by event type, SOC, PT, and subgroups (same as TEAEs) 
Item 3 will be listed and summarized by PT only. 
The preferred term list for these special safety events will be finalized prior to database lock. 
6.8.3. 
Clinical Laboratory Parameters 
Descriptive statistics for laboratory values (in SI units) and changes from baseline at selected 
visits will be presented for the following laboratory parameters. The number (%) of subjects by 
toxicity grades at selected visits will also be provided for selected lab tests. Shift tables for 
selected parameters from baseline to worst post-baseline will be provided. 


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Table 4: 
Laboratory Tests 
Hematology Panel: 
Absolute neutrophil count (ANC), Basophils, 
Eosinophils, Erythrocyte count (RBC), 
Hematocrit %, Hemoglobin, WBCs 
(Leukocyte count), Lymphocytes, Mean 
corpuscular volume, Monocytes, Neutrophils, 
Platelets 
Chemistry Panel: 
Bicarbonate, blood urea nitrogen (BUN), 
Calcium, Creatinine, Chloride, 
Magnesium, Glucose, ALP, ALT, AST, 
total Bilirubin, Albumin, Phosphorous, 
Potassium, Sodium, Cholesterol, Total 
Protein, GGT, Triglycerides 
Coagulation Panel: 
International Normalised Ratio (INR),  
partial thromboplastin time (aPTT/PTT) 
 
6.8.4. 
Liver Function Tests 
Liver function test results and the number (%) of subjects above 2×ULN or 3×ULN will be 
summarized over selected visits. 
A matrix scatter plot of liver enzymes and bilirubin showing the maximum ALT or AST vs. total 
bilirubin during treatment on natural-log scales with a dotted line drawn at 3×ULN for ALT or 
AST vs. at 2×ULN for total bilirubin will be provided. 
6.8.5. 
Vital Signs 
Heart rate (beat/min), diastolic and systolic blood pressure (mmHg), temperature (°C), and body 
weight (kg) will be descriptively summarized by treatment at selected visits. 
Vital sign values are potentially clinically significant (PCS) if they meet both the observed value 
criteria and the change from baseline criteria listed in Table 5 below. The number and percentage 
of subjects with post-baseline PCS values will be tabulated by treatment group. The percentages 
are to be calculated relative to the number of subjects with baseline and at least one post-baseline 
assessment. The numerator is the total number of subjects with at least one post-baseline PCS 
vital sign value. A supportive listing of subjects with post-baseline PCS values will be provided 
including the patient ID, study center, baseline, and post-baseline values. A listing of all AEs for 
subjects with PCS vital signs will also be provided. 


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Table 5: 
Criteria for Potentially Clinically Significant Vital Signs 
Vital Sign Parameter 
Flag 
Criteria* 
Observed Value 
Change from Baseline 
Systolic Blood Pressure (mmHg) 
High 
≥ 170 
Increase of ≥ 20 
Low 
≤ 90 
Decrease of ≥ 20 
Diastolic Blood Pressure (mmHg) 
High 
≥ 110 
Increase of ≥ 15 
Low 
≤ 45 
Decrease of ≥ 15 
Heart Rate (bpm) 
High 
≥ 120 
Increase of ≥ 20 
Low 
≤ 50 
Decrease of ≥ 20 
Weight (kg) 
High 
- 
Increase of ≥ 10% 
Low 
- 
Decrease of ≥ 10% 
*Except for body weight, a post-baseline value is considered as a PCS value if it meets both criteria for observed 
value and change from baseline. 
6.8.6. 
Electrocardiogram (ECG) 
ECG results (normal, abnormal-clinically significant, and abnormal-not clinically significant) 
will be summarized by treatment over visits. A shift table for ECG from baseline to worst post-
baseline will be provided. 
6.8.7. 
Physical Examination (PE) 
Abnormal PE results will be summarized by treatment over visits. A shift table will be provided 
if data is appropriate. A listing of abnormal PE results will be provided. 
6.8.8. 
Pregnancy Test 
Pregnancy tests for women of childbearing potential (WOCBP) only: serum pregnancy test at 
Screening; urine pregnancy tests (pre-dose) during study visits. 
A listing of positive pregnancy test results during study visits will be provided. 
6.9. 
Biomarker Endpoint Analysis 
All analyses for the exploratory biomarkers listed in Section 4.5 will be performed for the SAF 
based on observed data as appropriate. Descriptive summaries will be performed for the other 
exploratory biomarkers as appropriate. 
A listing will be provided for Tryptase at the time of any suspected hypersensitivity/ 
anaphylactic reactions, as defined in the protocol. 
6.10. 
Immunogenicity Analysis and PK 
Summary of immunogenicity data will be based on IGS and listings will be on SAF. The 
analysis dataset and data listing will include all available anti-drug antibody (ADA, also named 
HAHA) samples. The following terms and definitions are implemented. 


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6.10.1. 
Terms and Definitions 
6.10.1.1. Sample ADA Status 
• Baseline ADA-positive sample: ADA is detected in the last sample before initiation 
of treatment. 
• Baseline ADA-negative sample: ADA is not detected in the last sample before 
initiation of treatment. 
• Treatment-emergent ADA-Positive: Meets definition of treatment-induced or 
treatment-boosted ADA: 
− Treatment-induced ADA-Positive: a post-treatment positive ADA is detected in 
a subject for whom pre-treatment ADA assessment is either negative or not 
assessable 
− Treatment-boosted ADA-Positive: pre-existing ADA was boosted to a higher 
level following study treatment, i.e. pre-treatment positive ADA titer was boosted 
by at least 2 dilution steps (4-fold) following study treatment. 
• ADA-negative sample: After initiation of treatment, ADA is not treatment-emergent 
ADA-positive. 
Next, using the sample ADA status, the subject’s ADA status is defined. 
6.10.1.2. Subject ADA Status 
• Baseline ADA-positive subject: A subject with a baseline ADA-positive sample. 
• Baseline ADA-negative subject: A subject with a baseline ADA-negative sample. 
• ADA-positive subject: An evaluable subject with at least one treatment-emergent 
ADA-positive sample at any time during the study. 
• Neutralizing-positive: At least one treatment-emergent ADA-positive sample with 
neutralizing antibodies detected (if available). 
• ADA-negative subject: An evaluable patient without a treatment-emergent ADA 
sample during the study. 
• ADA-unknown: Patients without evaluable baseline and/or post-baseline ADA 
samples will be categorized as “ADA-unknown”. 
6.10.2. 
Statistical Analysis for Characterization of ADA Immune Response 
6.10.2.1. Incidence of ADA 
• Percentage of treatment-emergent ADA patients for the defined study period, where 
the denominator is the number of ADA evaluable patients in the respective treatment 
arm and/or subgroup. 


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• Number (%) of subjects will be reported for the following parameters based on 
evaluable subjects: 
− Baseline ADA-positive 
− Treatment-emergent ADA-positive (Treatment-induced, Treatment-boosted) 
− Neutralizing Positive (if available) 
− ADA-negative 
• ADA prevalence: Percentage of treatment-emergent ADA patients at any given 
timepoint, where the denominator is the number of ADA evaluable patients in the 
respective treatment arm and/or subgroup at that timepoint. 
• A listing of all ADA assessments will be provided. 
• Additionally, a separate listing of ADA assessments for all neutralizing antibody 
(NAb)-positive subjects will be provided (if available). 
6.10.2.2. ADA Titer Kinetics 
All ADA-positive subjects will be included in the analysis. 
• Summary statistics of subject-level ADA titers using the maximum titer value within 
an ADA-positive subject will be presented for baseline ADA-negative subjects and 
baseline ADA-positive subjects. The median, interquartile range, and range of the 
maximum titers will be reported. For ADA-positive subjects with a baseline ADA-
positive sample, the median and interquartile range of the fold increase from baseline 
in titer (ratio of maximum post-baseline titer to baseline titer) will also be reported. 
Graphical presentation of the summary data may be provided using boxplots, as 
appropriate. 
• For sample-level ADA titers, boxplots of ADA titers at each assessment time point 
will be provided, as appropriate, to demonstrate whether the ADA levels tend to 
change over time during the treatment, along with ADA incidence at each assessment 
time point. 
• Spider plots may be considered to show the trend of ADA titer over time. 
6.10.3. 
Clinical Implication of ADA Immune Response 
6.10.3.1. PK 
• Effect of ADA response on drug exposure will be explored by examining the drug 
exposures using graphical plots or simple summary statistics of observed drug 
concentration levels by ADA status and sampling time. Corresponding numerical 
values of geometric mean, arithmetic mean, and standard deviation will be displayed 
under the figures. 


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• A listing of drug concentrations will be provided. Time course of observed 
concentrations by study visit with identifiers for antibody response will be plotted for 
each subject separately. 
6.10.3.2. Safety and Efficacy 
• AEs and the primary efficacy endpoint will be summarized by ADA status (details in 
Section 6.7.1.4 and Section 6.8.1). 
7. 
CHANGES FROM PROTOCOL 
Based on the feedback from the Food and Drug Administration on a similar Phase 3 IPF study 
(protocol #: FGCL-3019-091), MMRM will be used as the primary analysis for FVC and RCM 
will be used as a sensitivity analysis. Supplemental and subgroup analyses for FVC will also use 
MMRM. The exploratory efficacy endpoint FVCpp will also be analyzed using MMRM. 
In addition, with consideration of FDA recommendations for the FGCL-3019-091 study, the 
testing order was switched for the following secondary efficacy endpoints: “Time to the first 
occurrence of any component of clinical composite endpoint: acute IPF exacerbation, respiratory 
hospitalization, or death, whichever occurs first” and “Change in QLF volume from baseline at 
Week 48” (Table 3). 
8. 
REFERENCE 
• E9(R1) Statistical Principles for Clinical Trials: Addendum: Estimands and 
Sensitivity Analysis in Clinical Trials 
• Eakin EG, Resnikoff PM, Prewitt LM, Ries AL, Kaplan RM., Validation of a new 
dyspnea measure: the UCSD Shortness of Breath Questionnaire. Chest. 1998; 
113:619-624 
• Jones, P.W., Quirk, F.H., Baveystock, C.M., and Littlejohns, P. A, Self-complete 
measure of health status for chronic airflow limitation. The St. George's Respiratory 
Questionnaire. Am Rev Respir Dis, 1992; 145: 1321–1327 
• Jones PW, Forde, Y., St George’s Respiratory Questionnaire Manual. 
http://www.healthstatus.sgul.ac.uk/SGRQ_download/SGRQ%20Manual%20June%2
02009.pdf. Accessed June 2, 2020 
• Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in 
idiopathic pulmonary fibrosis. N Engl J Med 2014; 370:2071-82. 
• Noble PW, Albera C, Bradford WZ, Costabel U, etc.; Pirfenidone in patients with 
idiopathic pulmonary fibrosis (CAPACITY): two randomised trials; Lancet 2011; 
377: 1760–69 


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• Statistical Review and Evaluation for Ofev® (nintedanib) 150 mg capsules; 
Indication: Treatment of Idiopathic Pulmonary Fibrosis (IPF); PDUFA: January 2, 
2015 
• King TE Jr., Bradford WZ, Castro-Bernardini S, etc.; A Phase 3 Trial of Pirfenidone 
in Patients with Idiopathic Pulmonary Fibrosis; N Engl J Med 2014;370:2083-92 
• Picozzi VJ, etc.; FG-3019, a human monoclonal antibody to connective tissue growth 
factor (CTGF), with gemcitabine/erlotinib (G/E) in patients with locally advanced or 
metastatic pancreatic ductal adenocarcinoma (PDAC). J. Cancer Clin Trials 2017, 2:1 
• Raghu G, etc.; Diagnosis of Idiopathic Pulmonary Fibrosis. An Official 
ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 
Sep 1;198(5):e44-e68. 
• The Acceptance of Overseas Drug Clinical Trial Data. NMPA 2018 
https://www.nmpa.gov.cn/zhuanti/ypqxgg/ggzhcfg/20180710151401465.html 
 


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APPENDIX 1. HANDLING MISSING/INCOMPLETE DATES 
Appendix 1.1 
Missing/Incomplete AE Onset Date 
The following imputation rules apply to the case where the start date is incomplete (i.e., partially 
missing) for adverse events. When the start date and the stop date are both incomplete for a 
patient, impute the start date first. 
If the stop date is complete and the imputed start date is after the stop date, then the start date 
will be imputed using the stop date. 
• Missing start time only 
AEs with missing start times and which occur on a study-drug-dosing day will be considered as 
occurred after the study treatment administration on that day. No imputation on other missing 
time. 
• Missing day and month 
If the year is the same as the year of the first day on double-blind study treatment, then the day 
and month of the start date of the double-blind study treatment will be assigned to the missing 
fields. 
If the year is different from the year of the first day on double-blind study treatment, then 
January 1 will be assigned to the missing fields. 
• Missing month only 
Treat day as missing and replace both month and day according to the above procedure. 
• Missing day only 
If the month and year are the same as the year and month of the first day of double-blind study 
treatment, then the start date of the double-blind study treatment will be assigned to the missing 
day. 
If the month and year are different from the year and month of the first day of double-blind study 
treatment, then the first day of the month will be assigned to the missing day. 
• Missing year 
No imputation. 
Appendix 1.2. 
Missing/Incomplete AE Stop Date 
If needed, the following imputation rules apply to the case where the end date is incomplete (i.e., 
partially missing) for adverse events. Other partial end dates will not be imputed. If the imputed 
stop date is before the start date (imputed or non-imputed start date), then the imputed stop date 
will be replaced with the start date. 
• Missing day and month, or Missing month only 


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December 31 will be assigned to the missing fields. If the imputed stop date is after the date of 
death, date of death will be used.  
• Missing day only 
If the month and year of the incomplete stop date are the same as the month and year of the last 
dose date of double-blind study treatment, then the day of the last dose date will be assigned to 
the missing day. 
If the month and year of the incomplete stop date are different from the month and year of the 
last dose date of double-blind study treatment, then the minimum of (the last day of the month, 
end of study date, date of death) will be assigned to the missing day. 
• Missing year 
No imputation. 
Appendix 1.3. 
Missing/Incomplete Prior or Concomitant Medication Start 
Date 
Same imputation rules as missing/incomplete AE onset date (Appendix 1.1).  
Appendix 1.4. 
Missing/Incomplete Prior or Concomitant Medication Stop 
Date 
Same imputation rules as missing/incomplete AE stop date (Appendix 1.2).  
Appendix 1.5. 
Missing Date Imputation for Last Dose Date 
Imputed last dose date = the earliest date of (last drug dispense date + the number of days of drug 
dispensed, date of death, date of end of treatment (EOT)/EOS visit, and other dates as 
appropriate). 


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APPENDIX 2. ANALYSIS VISIT WINDOWS 
Analysis visits are defined by the windows that will have the widths of the corresponding 
assessments centered at the scheduled time. Unscheduled visits within a visit window defined 
below will be grouped into the closest scheduled visits based on the visit date. 
Table 6: 
Analysis Visit Window for Vital Signs 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last value before the first study drug infusion 
(or randomization date if no infusion received) 
Day 1 postdose 
1 
1 
1 
Week 3 (predose and postdose) 
22 
2 
32 
Week 6 (predose and postdose) 
43 
33 
53 
Week 9 (predose and postdose) 
64 
54 
74 
Week 12 (predose and postdose) 
85 
75 
95 
Week 15 (predose and postdose) 
106 
96 
116 
Week 18 (predose and postdose) 
127 
117 
137 
Week 21 (predose and postdose) 
148 
138 
158 
Week 24 (predose and postdose) 
169 
159 
179 
Week 27 (predose and postdose) 
190 
180 
200 
Week 30 (predose and postdose) 
211 
201 
221 
Week 33 (predose and postdose) 
232 
222 
242 
Week 36 (predose and postdose) 
253 
243 
263 
Week 39 (predose and postdose) 
274 
264 
284 
Week 42 (predose and postdose) 
295 
285 
305 
Week 45 (predose and postdose) 
316 
306 
326 
Week 48 (predose and postdose) 
337 
327 
 351 [$] or *[@] 
28 Days post last dose [$] 
365 
Date of Last dosing+15 [$] 
* [$] 
$ For subjects who do not enroll OLE only. 
* End of the double-blind period (DBP). 
@ For subjects who enroll OLE. 
Note: The study day with infusions will be used for summary tables whenever possible. 
Note: If raw data shows visit is “28 Days post last dose”, then set analysis visit=visit 
Note: all assessments beyond 60 days post last infusion will be excluded from summary tables or figures. 
 
 


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Table 7: 
Analysis Visit Window for PFT 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last BTR PFT before the first study drug infusion (or randomization date if no infusion 
received) 
Week 6 
43 
2 
64 
Week 12 
85 
65 
106 
Week 18 
127 
107 
148 
Week 24 
169 
149 
211 
Week 36 
253 
212 
295 
Week 48 
337 
296 
End of DBP 
 
Table 8: 
Analysis Visit Window for HRCT 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last value before the first study drug infusion (or randomization date if no infusion 
received) 
Week 24 
169 
2 
253 
Week 48 
337 
254 
End of DBP 
Table 9: 
Analysis Visit Window for Labs 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last value before the first study drug infusion 
(or randomization date if no infusion received) 
Week 12 
85 
2 
127 
Week 24 
169 
128 
211 
Week 36 
253 
212 
295 
Week 48 
337 
296 
 351 [$] or *[@] 
28 days after last dose [$] 
365 
 Date of Last dosing+15 [$] 
* [$] 
$ For subjects who do not enroll OLE only. 
* End of the double-blind period. 
@ For subjects who enroll OLE. 
Note: If raw data shows visit is “28 Days post last dose”, then set analysis visit=visit 
Note: all assessments beyond 60 days post last infusion will be excluded from summary tables for labs. 


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Table 10: 
Analysis Visit Window for SGRQ, UCSD-SOBQ, LCQ, PE, and Weight 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last value before the first study drug infusion (or randomization date if no infusion received) 
Week 12 
85 
2 
127 
Week 24 
169 
128 
211 
Week 36 
253 
212 
295 
Week 48 
337 
296 
End of DBP 
Note: all assessments beyond 60 days post last infusion will be excluded from summary tables for PE. 
 
Table 11: 
Analysis Visit Window for ECG 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last value before the first study drug infusion (or randomization date if no infusion received) 
Week 48 
337 
2 
End of DBP 
Note: all assessments beyond 60 days post last infusion will be excluded from summary tables for ECG. 
 
Table 12: 
Analysis Visit Window for Biomarkers (Serum and Plasma) 
Analysis Visit 
Target Day 
Start Day 
End Day 
Day 1 
1 
1 
1 
Week 24 
169 
2 
253 
Week 48 
337 
254 
351 [$] or *[@] 
28 days Post last dose [$] 
365 
 Date of Last dosing+15 [$] 
* [$] 
$ For subjects who do not enroll OLE only. 
* End of the double-blind period. 
@ For subjects who enroll OLE. 
Note: If raw data shows visit is “28 Days post last dose”, then set analysis visit=visit 
Note: all assessments beyond 60 days post last infusion will be excluded from summary tables. 
 
 


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Table 13: 
Analysis Visit Window for CTGF and ADA (Plasma) 
Analysis Visit 
Target Day 
Start Day 
End Day 
Day 1 
1 
1 
1 
Week 24 
169 
2 
211 
Week 36 
253 
212 
295 
Week 48 
337 
296 
351 [$] or *[@] 
28 days Post last dose [$] 
365 
 Date of Last dosing+15 [$] 
* [$] 
$ For subjects who do not enroll OLE only. 
* End of the double-blind period. 
@ For subjects who enroll OLE. 
Note: If raw data shows visit is “28 Days post last dose”, then set analysis visit=visit 
Note: all assessments beyond 60 days post last infusion will be included in summary tables. 
 
Table 14: 
Analysis Visit Window for Pharmacokinetic Concentration (Plasma) 
Analysis Visit 
Target Day 
Start Day 
End Day 
Day 1 
1 
1 
1 
Day 8 
8 
2 
11 
Day 15 
15 
12 
18 
Week 3 
22 
19 
52 
Week 12 
85 
53 
127 
Week 24 
169 
128 
211 
Week 36 
253 
212 
295 
Week 48 
337 
296 
351 [$] or *[@] 
28 days Post last dose [$] 
365 
 Date of Last dosing+15 [$] 
* [$] 
$ For subjects who do not enroll OLE only. 
* End of the double-blind period. 
@ For subjects who enroll OLE. 
Note: If raw data shows visit is “28 Days post last dose”, then set analysis visit=visit 
Note: all assessments beyond 60 days post last infusion will be included in summary tables. 
 
 


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APPENDIX 3. SGRQ 
The SGRQ is designed to measure health impairment in patients with asthma and COPD. It is 
also valid for use in bronchiectasis and has been used successfully in patients with 
kyphoscoliosis and sarcoidosis. It includes Symptoms scores (questions 1-8), Activity scores 
(questions 11 and 15), and Impacts scores (questions 9-10, 12-14, and 16-17). A Total score is 
also calculated which summarizes the impact of the disease on overall health status. Scores are 
expressed as a percentage of overall impairment where 100 represents the worst possible health 
status and 0 indicates the best possible health status. 
Questions 1 – 7, 9, 10 &17 Where a patient has ticked a box, a value of 1 is entered for the 
appropriate question. The empty boxes are entered as 0. It will be noted that the questionnaire 
requests a single response to questions 1-7, 9-10, and 17. If multiple responses are given to one 
of these questions, then averaging the weights for the positive responses for that question is 
acceptable. 
Question 8 Where a patient has ticked ‘Yes’ to having a worse wheeze in the morning, a value 
of 1 is entered for the appropriate question. All other responses are entered as 0. 
Questions 11 – 16 Where a patient has ticked ‘True’, a value of 1 is entered for the appropriate 
question, and where a patient has ticked ‘False’ a value of 0 is entered. Where a patient has 
missed a question the cell on the spreadsheet is left blank. In response to question 14, if a patient 
is not receiving medication, then the response is zero, otherwise, the values are missing. 
Missing Questions 
The missing (blanks) in part 1 (Symptoms) will be imputed by an average of the multiple 
weighted responses in part 1. This imputation will adjust for up to 24% of missing items in the 
questionnaire. If more than 24% of items are missing, the component score will be ‘Missing’. 
Missed Items for Component Scores 
It is better not to miss items and any missing items are the fault of the experimenter, not the 
patient. The effect of missing items and recommendations from the scoring manual are the 
following: 
Symptoms Score: The Symptoms component will tolerate a maximum of 2 missed items from 
questions 1-8. 
Activity Score: The Activity component will tolerate a maximum of 4 missed items from 
questions 11 and 15. 
Impacts Score: The Impacts component will tolerate a maximum of 6 missed items from 
questions 9-10, 12-14, and 16-17. 
Therefore, if there are more than the recommended missed items described above the component 
score will be set to missing. If one of the component scores is missing, then the total score is 
missing. 
Outline of Scoring Algorithm 
• Principle of calculation 


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Each questionnaire response has a unique empirically derived 'weight'. The lowest possible 
‘weight’ is zero and the highest ‘weight’ is 100. 
• Each component of the questionnaire is scored separately in three steps: 
− The weights for all items with positive responses are summed. 
− The weights for missed items are deducted from the maximum possible weight for 
each component. The weights for all missed items are deducted from the 
maximum possible weight for the Total score. 
Sum of maximum possible weights for each component and Total: 
Component 
Questions 
# of tolerated 
maximum missing items 
Maximum 
Possible Weight 
Symptoms 
1 – 8 
2 
662.5 
Activity 
11 and 15 
4 
1209.1 
Impacts 
9 – 10, 12 – 14, 16 – 17 
6 
2117.8 
Total 
All 
 
3989.4 
(Note: these are the maximum possible weights that could be obtained for the worst possible 
state of the patient). 
− The score is calculated by dividing the summed weights by the adjusted 
maximum possible weight for that component and expressing the result as a 
percentage: 
Score = 100% x (Summed weights from positive items in that component/Sum of weights for 
all items in that component) 
The Total score is calculated similarly: 
Score = 100 x (Summed weights from positive items in the questionnaire/Sum of weights for 
all items in the questionnaire) 
Item Weights 
The following weights will be used to score the answers similar to the Excel-based system and 
other computerized scoring systems. Note that the wording of the item may not correspond 
exactly with the wording in the current version of the questionnaire. 
• PART 1 
1) Over the past 3 months, I have coughed: 
Response 
Weight 
almost every day 
80.6 
several days a week 
63.2 
a few days a month 
29.3 
only with respiratory infections 
28.1 
not at all 
0.0 
2) Over the past 3 months, I have brought up phlegm (sputum): 


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Response 
Weight 
almost every day 
76.8 
several days a week 
60.0 
a few days a month 
34.0 
only with respiratory infections 
30.2 
not at all 
0.0 
3) Over the past 3 months, I have had shortness of breath: 
Response 
Weight 
almost every day 
87.2 
several days a week 
71.4 
a few days a month 
43.7 
only with respiratory infections 
35.7 
not at all 
0.0 
4) Over the past 3 months, I have had wheezing attacks: 
Response 
Weight 
almost every day 
86.2 
several days a week 
71.0 
a few days a month 
45.6 
only with respiratory infections 
36.4 
not at all 
0.0 
5) How many times during the past 3 months have you suffered from severe or very 
unpleasant respiratory attacks? 
Response 
Weight 
more than 3 times 
86.7 
3 times 
73.5 
2 times  
60.3 
1 time  
44.2 
none of the time 
0.0 
6) How long did the worst attack of chest trouble last? 
Response 
Weight 
a week or more  
89.7 
3 or more days  
73.5 
1 or 2 days  
58.8 
less than a day  
41.9 
7) Over the past 3 months, in a typical week, how many good days (with few respiratory 
problems) have you had? 
Response 
Weight 
No good days 
93.3 
1 or 2 good days 
76.6 
3 or 4 good days 
61.5 
nearly every day was good 
15.4 
every day was good 
0.0 


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8) If you wheeze, is it worse when you get up in the morning? 
Response 
Weight 
No  
0.0 
Yes 
62.0 
• PART 2 
9) How would you describe your respiratory condition? 
Response 
Weight 
The most important problem I have  
83.2 
Causes me quite a lot of problem  
82.5 
Causes me a few problems  
34.6 
Causes no problem  
0.0 
10) If you have ever held a job: 
Response 
Weight 
My respiratory problems made me stop working altogether 
88.9 
My respiratory problems interfere with my job or made me change my job 
77.6 
My respiratory problems do not affect my job 
0.0 
11) Questions about what activities usually make you feel short of breath these days. 
Response 
Weight 
Sitting or lying still  
90.6 
Washing or dressing yourself 
82.8 
Walking around the house 
80.2 
Walking outside on level ground 
81.4 
Walking up a flight of stairs  
76.1 
Walking up hills  
75.1 
Playing sports or other physical activities 
72.1 
12) More questions about your cough and shortness of breath these days. 
Response 
Weight 
Coughing hurts 
81.1 
Coughing makes me tired 
79.1 
I am short of breath when I talk 
84.5 
I am short of breath when I bend over 
76.8 
My coughing or breathing disturbs my sleep 
87.9 
I get exhausted easily  
84.0 
13) Questions about other effects your respiratory problems may have on you these days. 
Response 
Weight 
My cough or breathing is embarrassing in public  
74.1 
My chest trouble is a nuisance to my family friends or neighbors  
79.1 
I get afraid or panic when I cannot catch my breath 
87.7 
I feel that I am not in control of my respiratory problems 
90.1 
I do not expect my respiratory problems to get any better 
82.3 
I have become frail or an invalid because of my respiratory problems 
89.9 


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Exercise is not safe for me  
75.7 
Everything seems too much of an effort  
84.5 
14) Questions about your respiratory treatment. 
Response 
Weight 
My treatment does not help me very much 
88.2 
I get embarrassed using my medication in public  
53.9 
I have unpleasant side effects from my medication  
81.1 
My medication interferes with my life a lot  
70.3 
15) Questions about how activities may be affected by your breathing. 
Response 
Weight 
I take a long time to get washed or dressed  
74.2 
I cannot take a bath or shower, or I take a long time to do it 
81.0 
I walk slower than other people my age, or I stop to rest  
71.7 
Jobs such as household chores take a long time, or I have to stop to rest 
70.6 
If I walk up one flight of stairs, I have to go slowly or stop  
71.6 
If I hurry or walk fast, I have to stop or slow down  
72.3 
My breathing makes it difficult to do things such as walk-up hills, carry things 
upstairs, light gardening such as weeding, dance, bowl or play golf  
74.5 
My breathing makes it difficult to do things such as carry heavy loads, dig in the 
garden or shovel snow, jog or walk briskly (5 miles per hour), play tennis or swim 
71.4 
My breathing makes it difficult to do things such as very heavy manual work, ride 
a bike, run, swim fast, or play competitive sports 
63.5 
16) We would like to know how your respiratory problems usually affect your daily life. 
Response 
Weight 
I cannot play sports or do other physical activities  
64.8 
I cannot go out for entertainment or recreation  
79.8 
I cannot go out of the house to do the shopping  
81.0 
I cannot do housework chores 
79.1 
I cannot move far from my bed or chair  
94.0 
 
17) Tick the statement which you think best describes how your chest affects you. 
Response 
Weight 
It does not stop me from doing anything I would like to do  
0.0 
It stops me from doing one or two things I would like to do  
42.0 
It stops me from doing most of the things I would like to do  
84.2 
It stops me from doing everything I would like to do  
96.7 


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APPENDIX 4. UCSD-SOBQ 
The SOBQ asks subjects to indicate the severity of shortness of breath on a 6-point scale (0 = 
Not at all, to 5 = Maximally or unable to do because of breathlessness) during 21 activities of 
daily living associated with varying levels of exertion. Three additional questions ask about fear 
of harm from overexertion, limitations, and fear caused by shortness of breath, for a total of 24 
items. If patients do not routinely perform an activity, they are asked to estimate their anticipated 
shortness of breath. The SOBQ is scored by summing non-missing responses across all 24 
items to form a total score. A total sum score ranges from 0 to 120, with higher scores indicating 
greater dyspnea. 
If 22-23 questions were answered, the total SOBQ score will be the sum of non-missing 
questions*24/number of questions answered assuming missing items is neutral. If 21 or fewer 
questions were answered, the SOBQ score will be set to missing. 


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APPENDIX 5. LCQ 
The LCQ is a 19 Response questionnaire that assesses cough-related QOL. It has 3 domains 
(physical, psychological, and social): 
• Physical: Questions 1, 2, 3, 9, 10, 11, 14, 15 
• Psychological: Questions 4, 5, 6, 12, 13, 16, 17 
• Social: Questions 7, 8, 18, 19 
The total score range is 3 to 21 and domain scores range from 1 to 7; a higher score indicates a 
better quality of life. Scores are calculated as a mean of each domain and the total score is 
calculated by adding every domain score. Only non-missing scores are considered in the mean 
domain score calculation. Two missing values are allowed for Physical, and 1 missing value is 
allowed for Social and Psychological domains. Total scores require non-missing scores for 3 
domains. 


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APPENDIX 6. GAP SCORE AND STAGE 
GAP index and staging system for IPF: gender (G), age (A), and two pulmonary physiological 
parameters (P)—percentage predicted FVC [%], and percentage predicted DLCO [%]. 
GAP Stage I: 0-3 points; Stage II: 4-5 points; Stage III: 6-8 points. 
 
Predictor 
Points 
G: Gender 
Female 
0 
Male 
1 
A: Age (years) 
≤60 years 
0 
61-65 years 
1 
>65 years 
2 
P: Predicted Forced Vital Capacity (FVCpp) 
>75% 
0 
50-75% 
1 
<50% 
2 
P: Predicted Diffusing Capacity of the Lung for 
Carbon Monoxide (DLCOpp) 
>55% 
0 
36-55% 
1 
≤35%* 
2 
Cannot perform 
3 
Total Possible Points 
8 
*Value < 35.5 is rounded down to 35; value>=35.5 is rounded up to 36. 


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APPENDIX 7. EXAMPLE SAS CODE 
Appendix 7.1. MMRM 
Sample SAS code for MMRM: 
PROC MIXED DATA=mmrm; 
 
CLASS trtp randomization_factor avisit subjid; 
MODEL chg = trtp avisit trtp*avisit covariates randomization_factor/DDFM=kr; 
 
REPEATED avisit/SUBJECT=subjid TYPE=UN GROUP=trtp; 
 
LSMEANS trtp/PDIFF CL; 
 
LSMEANS trtp*avisit/PDIFF CL; 
RUN; 
Appendix 7.2. Jump-to-Control 
Under the jump-to-control assumption, the analysis will be carried out in 3 steps. 
Step 1 - the missing FVC data will be imputed to derive 200 imputed datasets with non-missing 
data according to the jump-to-control data pattern. 
Sample SAS code: 
/*generate a monotone missing data pattern*/ 
PROC MI DATA=aval OUT=xx1 SEED=9978 NIMPUTE=200 ROUND=0.001 MINIMUM=0.5 MAXIMUM=7; 
 
BY trtp; 
 
VAR base week6 week12 week18 week24 week36 week48; 
 
MCMC CHAIN=multiple IMPUTE=monotone; 
RUN; 
 
PROC SORT DATA=xx1; 
 
BY _imputation_ subjid; 
RUN; 
 
/*Generate MI datasets with non-missing data via a Jump-to-Control approach*/ 
PROC MI DATA=xx1 SEED=1482 NIMPUTE=1 OUT=mnar; 
 
CLASS trtp; 
 
BY _IMPUTATION_; 
 
VAR base week6 week12 week18 week24 week36 week48; 
MONOTONE REG (trtp base week6 week12 week18 week24 week36 week48); 
MNAR model (week6 week12 week18 week24 week36 Week48/ 
MODELOBS=(trtp='Placebo')); 
RUN; 
Step 2 - The 200 multiple-imputation datasets with imputed and observed FVC data at Week 48 
will be analyzed separately for each imputation using the ANCOVA method. The ANCOVA 
model will contain terms for treatment, baseline FVC measurements, covariates (age, sex, race 
group, and height), and the randomization stratification factor. The LSMean and corresponding 
SE for the change from baseline in FVC at Week 48 will be estimated. 
Sample SAS code: 
PROC MIXED data=mnar; 
 
BY _imputation_; 
 
CLASS trtp randomization_factor; 
MODEL chg_wk48 = trtp base covariates randomization_factor/SOLUTION DDFM=kr; 
 
LSMEANS trtp / PDIFF CL; 
 
ODS OUTPUT DIFFS=lsdiffs LSMEANS=lsm SOLUTIONF=parms; 


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RUN; 
Step 3 - The SAS PROC MIANALYZE will be used to derive the final estimates and test 
statistics summarizing these 200 analysis results. 
Sample SAS code: 
PROC SORT DATA=lsm; 
 
BY trtp; 
RUN; 
 
PROC MIANALYZE DATA=lsm; 
 
BY trtp; 
 
MODELEFFECTS estimate; 
 
STDERR; 
 
ODS OUTPUT ParameterEstimates=lsm2; 
RUN; 
 
PROC MIANALYZE DATA=lsdiffs; 
 
MODELEFFECTS estimate; 
 
STDERR; 
 
ODS OUTPUT ParameterEstimates=lsdiffs2; 
RUN; 
Appendix 7.3. Delta-Adjusting (Tipping Point) Analysis 
The multiple imputations for tipping point analysis will be performed as follows. 
Step 1 - the missing FVC data will be imputed to derive 200 imputed datasets with non-missing 
data according to the delta-adjusting data approach. 
Sample SAS code: 
/*generate a monotone missing data pattern*/ 
PROC MI DATA=aval OUT=xx1 SEED=9978 NIMPUTE=200 ROUND=0.001 MINIMUM=0.5 MAXIMUM=7; 
 
BY trtp; 
 
VAR base week6 week12 week18 week24 week36 week48; 
 
MCMC CHAIN=multiple IMPUTE=monotone; 
RUN; 
 
PROC SORT DATA=xx1; 
 
BY _imputation_ subjid; 
RUN; 
 
%let sft=-0.3;/*Define a macro for shift value, adjust the value in SAS code*/ 
 
/*Generate MI datasets with non-missing values using the tipping point approach*/ 
PROC MI DATA=xx1 SEED=1482 NIMPUTE=1 OUT=tipping; 
 
CLASS trtp; 
 
BY _IMPUTATION_; 
 
VAR trtp base week6 week12 week18 week24 week36 week48; 
 
MONOTONE REG (base week6 week12 week18 week24 week36 week48); 
 
MNAR ADJUST(week6 / SHIFT=&sft ADJUSTOBS=(trtp='Pamrevlumab')); 
 
MNAR ADJUST(week12 / SHIFT=&sft ADJUSTOBS=(trtp='Pamrevlumab')); 
MNAR ADJUST(week18 / SHIFT=&sft ADJUSTOBS=(trtp='Pamrevlumab')); 
 
MNAR ADJUST(week24 / SHIFT=&sft ADJUSTOBS=(trtp='Pamrevlumab')); 
 
MNAR ADJUST(week36 / SHIFT=&sft ADJUSTOBS=(trtp='Pamrevlumab')); 
 
MNAR ADJUST(week48 / SHIFT=&sft ADJUSTOBS=(trtp='Pamrevlumab')); 
RUN; 


FGCL-3019-095 (ZEPHYRUS 2)  
  
 
Statistical Analysis Plan (V1.0, Double-blind Period)  
 
Confidential 
Page 55 of 56 
 
 
Step 2 – The 200 multiple imputation datasets will be analyzed separately using the same 
ANCOVA model as Step 2 in Appendix 7.2.  
Step 3 – Same as Step 3 in Appendix 7.2. 
Appendix 7.4. Ranked ANCOVA 
Sample SAS code for Ranked ANCOVA: 
PROC RANK OUT=ranked TIES=mean; 
 
WHERE avisit=’Week 48’; 
 
VAR base chg;/*Missing chg was imputed*/ 
RUN; 
 
PROC MIXED DATA=ranked; 
 
CLASS sex randomization_factor; 
 
MODEL chg= base age height race sex randomization_factor/OUTP=residual; 
RUN; 
 
PROC FREQ DATA=residual; 
 
TABLES trtp*resid / NOPRINT CMH2; 
 
OUTPUT OUT=rancova CMH2; 
RUN; 
 


FGCL-3019-095 (ZEPHYRUS 2)  
  
 
Statistical Analysis Plan (V1.0, Double-blind Period)  
 
Confidential 
Page 56 of 56 
 
 
APPENDIX 8. CHINA CDE REQUIREMENT 
Efficacy data, mainly including overseas key clinical trial data and clinical trial data conducted 
in China, should not only confirm the efficacy of the study drug as a whole, but also analyze the 
consistency between Chinese subgroups and the overall population. 
Safety data, including all domestic and foreign data used for safety evaluation, should be 
analyzed not only for overall safety but also for consistency between Chinese subgroup and 
overall population. 
All TLF in China may be provided per China regulatory requirements if regulatory submission in 
China is pursued (NMPA guidance). 
 


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