Clinical trial NCT04432298
Conditions: COVID-19
Keywords: Severe Acute Respiratory Syndrome coronavirus SARS-COV-2 infection
Sponsor: FibroGen
Start date: 2020-06-20; Completion date: 2021-03-22
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates the efficacy and safety of intravenous (IV) infusions of pamrevlumab when compared with placebo in participants who are hospitalized with acute COVID-19 disease.

Detailed description:
This is a randomized, double-blind, placebo-controlled, phase 2, proof-of-concept study to evaluate the efficacy and safety of IV pamrevlumab, a monoclonal antibody, against connective-tissue growth factor (CTGF), in participants hospitalized with acute COVID-19 disease.

All concomitant medications, including approved and non-approved treatments for COVID-19 (such as, hydroxychloroquine or interleukin 6 \[IL-6\] inhibitors), as well as supplemental oxygenation needs, will be collected and recorded. In addition, the following will be collected and recorded: documentation of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov-2) infection, documentation of any other infection(s) prior to or during hospitalization, and whether or not aggressive care is withheld or withdrawn, including the reason for withholding or withdrawal of care (such as a Do Not Resuscitate/Do Not Intubate \[DNR/DNI\] order or a resource limitation).

Arms: arm 1: Pamrevlumab: 35 milligrams/kilogram (mg/kg) on Days 1, 7, 14 and 28 for a total of 4 infusions over 4 weeks arm 2: Pamrevlumab-matching placebo on Days 1, 7, 14 and 28 for a total of 4 infusions over 4 weeks
Interventions: intervention 1: Pamrevlumab intervention 2: Placebo
Intervention descriptions: intervention 1: Sterile liquid for injection intervention 2: Sterile liquid for injection

Protocol documents:
Prot_000.pdf: 
Page 1 of 84 
Synoptic Clinical Study Report 
FGCL-3019-098 
16.1 Study Information 
1.
PROTOCOL AND AMENDMENTS
ORIGINAL PROTOCOL: 
01 May 2020 
PROTOCOL AMEDMENT 1.0: 
12 May 2020 
1 
NCT #NCT04432298


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CLINICAL STUDY PROTOCOL 
 
STUDY TITLE: 
Randomized, Double-Blind, Placebo-Controlled 
Phase 2 Study of the Efficacy and Safety of 
Intravenous Pamrevlumab, a Monoclonal Antibody 
Against Connective Tissue Growth Factor (CTGF), 
in Hospitalized Patients with Acute COVID-19 
Disease 
 
PROTOCOL NUMBER: 
FGCL-3019-098 
 
PHASE: 
Phase 2 
 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
 
KEY SPONSOR CONTACTS: 
Name: 
 
Title: 
 
Telephone: 
 
Mobile: 
 
E-mail Address: 
 
Name: 
 
Title: 
 
Telephone: 
 
Mobile: 
 
E-mail Address: 
 
IND NUMBER: 
149628 
 
STUDY DRUG: 
Pamrevlumab (FG-3019) 
 
INDICATION: 
Hospitalized patients with acute COVID-19 disease 
due to confirmed SARS-CoV-2  infection 
 
ORIGINAL PROTOCOL: 
01 May 2020 
 
 
 
 
 
 
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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INVESTIGATOR SIGNATURE PAGE 
STUDY ACKNOWLEDGEMENT 
 
Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Efficacy and Safety of 
Intravenous Pamrevlumab, a Monoclonal Antibody Against Connective Tissue Growth Factor 
(CTGF), in Hospitalized Patients with Acute COVID-19 Disease 
FGCL-3019-098 
 
Original: 01 May 2020 
 
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 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. 


D o c u Si g n  E n v el o p e  I D: 2 3 1 1 6 5 4 0 -3 D 4 C -4 D E 3 -8 3 1 B -A 8 B D 6 A 5 5 B A 8 6  
Pa mre vl u ma b  
F G C L -3 0 1 9 -0 9 8  
C o nfi de ntial  
Pa ge  3  of 4 2  
Pa ge  3  of  8 4  
 
 
 
C O N FI R M A TI O N  O F  P R O T O C O L  A P P R O V A L  
Ori gi nal Pr ot oc ol Date: 0 1 Ma y 2 0 2 0 
T his  pr ot oc ol is a p pr o ve d b y Fi br o Ge n. 
 
 
 
 
 
 
 
 
 
: 5 9 : 1 5  P D T  
 
 
 
 
 
 
Fi br o Ge n, I nc. 
 
Date  
- M a y - 2 0  I  1 3  
 


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1. 
PROTOCOL SYNOPSIS 
 
 
PROTOCOL SYNOPSIS 
Study Title: 
Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of 
the Efficacy and Safety of Intravenous Pamrevlumab, a 
Monoclonal Antibody Against Connective Tissue Growth Factor 
(CTGF), in Hospitalized Patients with Acute COVID-19 Disease 
Protocol Number: 
FGCL-3019-098 
Investigational Product: 
Pamrevlumab (FG-3019) 
Study Phase: 
Phase 2 
Indication: 
Hospitalized patients with acute COVID-19 disease due to 
confirmed SARS-COV-2 infection 
Number of 
Subjects Planned: 
Approximately 130 
Number of Sites Planned: 
Approximately 5-10 in the USA 
OBJECTIVES 
To assess the efficacy and safety of pamrevlumab, an investigational monoclonal antibody against 
connective tissue growth factor (CTGF), compared to placebo, in hospitalized patients with acute 
COVID-19 disease due to confirmed SARS-COV-2 infection. 


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Endpoints 
Efficacy Assessments: 
Primary Efficacy Endpoint 
Proportion of subjects alive and never received mechanical ventilation at Day 14 
Secondary Efficacy Endpoints 
• Proportion of subjects alive, discharged home, and not on supplemental oxygen at Day 28 
• Time to recovery by Day 28 based on 8-point ordinal scale (Day of recovery is defined as 
the first day on which the patient satisfies one of the following three categories from the 
ordinal scale: 1) Hospitalized, not requiring supplemental oxygen; 2) Not hospitalized 
(discharged), but with limitation on activities and/or requiring home supplemental oxygen; 
3) Not hospitalized (discharged), with no limitations on activities and not requiring 
supplemental oxygen 
• Clinical status based on 8-point ordinal scale (time range: Days 1 to 28) 
• Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28 
• Days on mechanical ventilation and/or ECMO at Day 28 
• Time to mechanical ventilation/ECMO or all-cause mortality at Day 28 
• All-cause mortality at Day 28 (proportion of subjects deceased) 
• Time to death from any cause at Day 28 
• Change in PaO2/FiO2 ratio as categorical variable using Berlin criteria for ARDS 
categorization (mild, moderate, severe) (time range: Days 1 to 28) 
• Change in PaO2/FiO2 ratio as continuous variable (time range: Days 1 to 28) 
• Change in resting SpO2 adjusted by FiO2 (time range: Days 1 to 28) 
• Change in (non-invasive) oxygen supplementation requirements (time range: Days 1 to 28) 
Safety Assessments: 
Treatment-emergent adverse events (TEAEs); treatment-emergent serious adverse events 
(TESAEs), including hypersensitivity/ anaphylactic reactions; clinical laboratory parameters and 
vital signs. 
STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled phase 2 study to evaluate the efficacy and 
safety of intravenous pamrevlumab, a monoclonal antibody against connective-tissue growth 
factor (CTGF), in hospitalized subjects with acute COVID-19 disease. 
Eligible subjects are those with documented SARS-CoV-2 infection, age 40 to 85 years, with 
evidence of respiratory compromise requiring hospital admission. This age range was chosen to 


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enhance detection of potential clinical benefits in subjects at highest risk for developing severe 
COVID-19 disease in this proof-of-concept study. 
Approximately 130 subjects will be randomized in a 1:1 ratio to either pamrevlumab or placebo; 
all subjects will also receive standard-of-care in the judgment of the Investigator. 
Study drug administration is via IV infusion on Days 1 (day of randomization), 7, 14 and 28. A 
follow-up by visit will be performed 4 weeks after the last dose. 
All concomitant medications, including approved and non-approved treatments for COVID-19 
(e.g., hydroxychloroquine, IL-6 inhibitors, etc.), as well as supplemental oxygenation needs, will 
be collected and recorded. In addition, the following will be collected and recorded: documentation 
of SARS-Cov-2 infection, documentation of any other infection(s) prior to or during 
hospitalization, and whether or not aggressive care is withheld or withdrawn, including the reason 
for withholding or withdrawal of care (e.g., DNR/DNI order, resource limitation). 
STUDY PERIODS 
Screening Period: Up to 2 days prior to randomization 
Treatment Period: 28 days 
Follow-Up Period: 28 days after last dose 
SUBJECT ELIGIBILITY CRITERIA 
Inclusion Criteria: 
1. Age 40-85 years 
2. Confirmed SARS-CoV-2 infection by a FDA-authorized diagnostic test (e.g., polymerase 
chain reaction [PCR] or other approved assay from any specimen source; note: a positive 
serology/antibody test for SARS-CoV-2 does NOT qualify as evidence of acute COVID- 
19 disease) 
3. Respiratory compromise requiring hospitalization for COVID-19 disease as evidenced by 
at least one (or more) of the following criteria: 
a. Interstitial pneumonia on CXR or HRCT (findings of consolidation or ground glass 
opacities), OR 
b. Peripheral capillary oxygen saturation (SpO2) < 94% on room air, OR 
c. Requiring non-invasive supplemental oxygen (e.g., nasal cannula, face mask) to 
maintain SpO2 
4. Not requiring mechanical ventilation and/or extracorporeal membrane oxygenation 
(ECMO) use at time of randomization 
5. Agrees to not participate in another clinical trial for the treatment of COVID-19 disease 
through Day 28 
6. Subject (or legally authorized representative) able to understand and sign a written 
informed consent form 


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Exclusion Criteria: 
1. Female subjects who are pregnant or nursing 
2. Participation in a clinical trial with another investigational drug for COVID-19 disease 
3. Anticipated discharge from the hospital or transfer to another hospital or long-term care 
facility which is not a study site within 72 hours of randomization 
4. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies 
STUDY TREATMENT 
Dose and mode of administration 
Dose: 35 mg/kg IV 
Dosing regimen: Days 1, 7, 14 and 28. 
Other important information 
Study drug should not be administered to subjects with a history of allergic or anaphylactic 
reaction to human, humanized, or chimeric monoclonal antibodies. 
STATISTICAL METHODS 
Determination of sample size 
The sample size of 65 subjects in each treatment arm will provide approximately 80% power, at 
10% two-sided significance level, to detect a 20% absolute difference in the proportion of subjects 
alive and never received mechanical ventilation at Day 14. This assumes that 65% of subjects in 
the placebo arm are alive and never received mechanical ventilation at Day 14 compared to 85% 
in the pamrevlumab group. 
Randomization 
Subjects who meet all eligibility criteria during screening will be randomized in a 1:1 ratio 
(pamrevlumab vs placebo) centrally across all sites and based on a pre-determined randomization 
list from a permuted block design. 
Statistical analysis methods 
The analysis of the proportion of subjects alive and never received mechanical ventilation at Day 
14, the proportion of subjects alive, discharged home, and not on supplemental oxygen at Day 28, 
proportion of subjects’ clinical status based on an 8-point ordinal scale, and proportion of subjects 
with categorical PaO2/FiO2 ratio endpoints will be conducted using logistic regression model with 
treatment group and adjusting for relevant baseline prognostic covariates. 
The number of days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 
28, number of days on mechanical ventilation and/or ECMO at Day 28 will be analyzed using the 
analysis of covariance (ANCOVA). 
Change in PaO2/FiO2 ratio to day 28, change in resting SpO2 adjusted by FiO2 to day 28, change in 
(non-invasive) oxygen supplementation requirements to day 28 will be analyzed using Mixed 


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Model for Repeated Measures (MMRM) approach using relevant prognostic factors as covariates 
and treatment and Time and treatment *time interaction. 
The analysis will take into account the inter-current events as follows. 
1. Treatment discontinuation (e.g., due to AEs, Withdrawal by Subject or Physician 
Decision): Missing endpoint will be imputed by the last result prior to discontinuation. 
2. Death: Composite strategy: inter-current event is taken to be a component of the variable. 
For number of days not requiring mechanical ventilation at Day 14, number of days in 
ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28, and number 
of days on mechanical ventilation and/or ECMO at Day 28; days with missing data after 
death will be imputed with the worst result until Day 28. 
3. Treatment discontinuation due to recovering and discharged from hospital: Missing 
endpoint will be imputed with the last result prior to discontinuation. 
Treatment comparison analysis of time to event endpoints, will be performed using cox regression 
model adjusting for relevant baseline prognostic factors. Hazard ratios together with 95% two- 
sided confidence intervals for the hazard ratio will be provided. 
Time to recovery by Day 28, time to mechanical ventilation/ECMO or all-cause mortality by Day 
28, and all-cause mortality at Day 28 (proportion of subjects deceased), and time to death from 
any cause at Day 28 will be analyzed using Cox regression adjusting for relevant prognostics 
factors. Other methods will be used as appropriate. 
Safety analyses 
All subjects who received any dose of pamrevlumab will be included in the safety population 
analyses which will summarize treatment-emergent adverse events (TEAEs); treatment-emergent 
serious adverse events (TESAEs), including hypersensitivity/ anaphylactic reactions; clinical 
laboratory parameters and vital signs. 
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 
1. 
PROTOCOL SYNOPSIS .............................................................................................4 
2. 
INTRODUCTION ......................................................................................................12 
2.1. 
Description of Pamrevlumab ......................................................................................12 
2.2. 
Background Information and Study Rationale ...........................................................12 
2.2.1. 
Connective Tissue Growth Factor (CTGF) .................................................................12 
2.2.2. 
Study Rationale ...........................................................................................................12 
2.3. 
Summary of Past Clinical Studies, Safety and Dosing Information ...........................14 
2.3.1. 
Clinical efficacy in completed studies: .......................................................................16 
2.4. 
Ongoing clinical study in patients with SARS-CoV-2 Infection. .............................. 16 
3. 
OBJECTIVES AND ASSESSMENTS...................................................................... 17 
3.1. 
Objective .....................................................................................................................17 
3.2. 
Efficacy Assessments .................................................................................................17 
3.3. 
Safety Assessments .....................................................................................................17 
4. 
OVERALL STUDY DESIGN ....................................................................................18 
4.1. 
Subject ID Assignment ...............................................................................................18 
4.2. 
Randomization ............................................................................................................18 
4.3. 
Blinding ......................................................................................................................18 
4.3.1. 
Request for Unblinding of Treatment Assignment .....................................................19 
4.4. 
Study Duration ............................................................................................................19 
5. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................20 
5.1. 
Inclusion Criteria ........................................................................................................20 
5.2. 
Exclusion Criteria .......................................................................................................20 
5.3. 
Study Withdrawal Criteria ..........................................................................................20 
5.4. 
Replacement of Study Subjects ..................................................................................21 
5.5. 
Study Closure. .............................................................................................................21 
6. 
STUDY ASSESSMENTS ..........................................................................................22 
6.1. 
Laboratory Assessments, including ABG and SpO2 ..................................................22 
6.2. 
Modified WHO Ordinal Scale ....................................................................................22 
6.3. 
Concomitant Medications, Supplemental Oxygen Needs, and other Care .................22 
7. 
STUDY DRUG ...........................................................................................................23 
7.1. 
Study Drug Packaging and Labeling ..........................................................................23 


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7.2. 
Study Drug Storage. ....................................................................................................23 
7.3. 
Study Drug Preparation...............................................................................................23 
7.4. 
Study Drug Administration. ........................................................................................23 
7.5. 
Study Drug Handling and Disposal ............................................................................24 
8. 
ASSESSMENTS OF SAFETY ..................................................................................25 
8.1. 
Background .................................................................................................................25 
8.2. 
Definitions ..................................................................................................................25 
8.2.1. 
Definition of an Adverse Event (AE) ........................................................................ 25 
8.2.2. 
Definition of a Serious Adverse Event (SAE) ........................................................... 25 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events .........................26 
8.3.1. 
Adverse Event Reporting Period ................................................................................26 
8.3.2. 
Adverse Event Eliciting/Reporting .............................................................................26 
8.3.3. 
Assessing Adverse Event Severity .............................................................................27 
8.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug ......................................27 
8.3.5. 
Reporting Serious Adverse Events (SAEs) ................................................................28 
8.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review Board / 
Independent Ethics Committee ...................................................................................29 
8.3.5.2. 
Deaths .........................................................................................................................29 
8.3.6. 
Pregnancies: Reporting and Follow-up of Subjects and Female Partners of 
Subjects .......................................................................................................................29 
8.3.7. 
Laboratory or other Test Abnormalities/ Findings .....................................................30 
8.3.8. 
Hypersensitivity/Anaphylactic Reactions: ..................................................................30 
8.3.9. 
Safety Monitoring .......................................................................................................31 
8.3.9.1. 
Special Reporting Situations ...................................................................................... 31 
9. 
STATISTICS ..............................................................................................................32 
9.1. 
Sample Size Determination ........................................................................................32 
9.2. 
Analysis Populations .................................................................................................. 32 
9.3. 
General Considerations ...............................................................................................32 
9.4. 
Statistical Methods. .....................................................................................................32 
9.5. 
Safety Analyses...........................................................................................................33 
10. 
ETHICS ......................................................................................................................34 
10.1. 
Ethical Considerations ................................................................................................34 
10.2. 
Communication with the Institutional Review Board or Independent Ethics 


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Committee. ..................................................................................................................34 
10.3. 
Subject Information and Consent ...............................................................................35 
10.4. 
Confidentiality ............................................................................................................35 
11. 
DATA HANDLING AND RECORD KEEPING ......................................................36 
11.1. 
Source Documents ......................................................................................................36 
11.2. 
Direct Access to Source Documents ...........................................................................36 
11.3. 
Data Collection, Handling, and Verification ..............................................................36 
11.4. 
Protocol Deviations .....................................................................................................36 
11.5. 
Retention of Data ........................................................................................................37 
11.6. 
Financial Disclosure .................................................................................................. 37 
12. 
PUBLICATION POLICY ..........................................................................................38 
13. 
REFERENCES ...........................................................................................................39 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................42 


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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 (e.g, 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.
Background Information and Study Rationale
2.2.1.
Connective Tissue Growth Factor (CTGF)
CTGF is a 38 kDa secreted matricellular glycoprotein of the cysteine-rich
61/CTGF/nephroblastoma overexpression family (Perbal, 2004, Rachfal, 2005) which was
recently renamed cellular communication network (CCN) family (Perbal 2018). It is produced by
many cells, including fibroblasts, myofibroblasts, endothelial cells, mesangial cells, and stellate
cells.
CTGF is a central mediator of tissue remodeling and fibrosis (Lipson, 2012). CTGF is essential
for the fibrotic activity of TGF-B (Mori, 1999, Wang, 2011) but it may also act independently of
TGF-B. While much has been made of the role of TGF-B in fibrosis, studies of the role of
fibronectin in pulmonary fibrosis showed that the activity of TGF-B is dependent on cellular
fibronectin to induce myofibroblast differentiation and that cellular fibronectin may have a
fundamental role in activation of latent TGF-B (Muro, 2008). Shi-wen and colleagues showed
that critical activities of TGF-B 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-B (Shi-wen, 2006).
CTGF has been shown to be an important mediator of pulmonary fibrosis in a mouse model of
bleomycin-induced pulmonary fibrosis (
, 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).
2.2.2.
Study Rationale
Recent data indicate the presence of interstitial pneumonia (consolidation or ground glass
opacities) in a subset of patients infected with novel coronavirus SARS-CoV-2 requiring
hospitalization. The interstitial pneumonia is usually bilateral and responsible for reduced
efficiency of gas exchange, potentially leading to respiratory failure, intubation and finally death
in a significant proportion of patients requiring mechanical ventilation. CTGF (connective tissue
growth factor; CCN2) may promote vascular leakage, and administration of pamrevlumab, an
investigational anti-CTGF monoclonal antibody, can reverse edema. Using the Miles assay,
CTGF promoted vascular leakage in skin (Data on file, generated by FibroGen). In rodent
models of complications of diabetes, the abundance of CTGF in urine correlated to the extent of


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albuminuria (Roestenberg et al. 2006; FibroGen Report 200_04_3050_034). Pamrevlumab was 
shown to inhibit vascular leakage in the lungs after irradiation (Bickelhaupt et al. 2017), and in 
several organs in complications of diabetes models (data on file at FibroGen), as well as to 
suppress ascites in a genetically engineered model of pancreatic cancer (Neesse et al. 2013). 
These observations suggest that administration of pamrevlumab may attenuate edema associated 
with the virus-induced pneumonia and improve gas exchange. 
In addition, published data in several animal models (Pi et al. 2018; Bickelhaupt et al. 2017; 
Sternlicht et al. 2018; Makino et al. 2017; Booth et al. 2010) indicate that pamrevlumab alters 
trafficking of certain immune-related cells. In a mouse radiation-induced lung fibrosis (RILF) 
model, the mechanism by which pamrevlumab-treated mice experienced a rapid reversal of 
pneumonitis appears to be deactivation of myofibroblasts resulting in decreased secretion of 
inflammatory chemokines (Sternlicht et al. 2018). This hypothesis remains to be confirmed for 
the RILF model, and the mechanism(s) by which pamrevlumab alters immune cell trafficking 
remains to be determined. It should also be noted that none of these models involved active viral 
infections, so it is unclear if pamrevlumab would broadly affect inflammation associated with 
SARS-Cov-2 infection resulting in COVID-19 disease. However, if blocking CTGF attenuates 
inflammation, pamrevlumab might reduce symptoms associated with the virus-induced cytokine 
storm. 
In addition to lung damage caused by the immune system’s hyperactive attempt to eradicate the 
viral infection, invasive mechanical ventilation of ARDS patients may also contribute to 
development of pulmonary fibrosis (Cabrera-Benitez et al. 2014). In ARDS patients that 
developed fibrosis, there was a statistically significant correlation between ventilator settings and 
the abundance of TGFB and CTGF in serum (Xie et al. 2019). CTGF has been shown to be 
elevated in ventilated pre-term sheep, and to increase with gas volume (Wallace et al. 2009) and 
flow (Bach et al. 2008). CTGF expression also increases with tidal volume in neonatal rats (Wu 
et al. 2008). In ventilator-induced lung injury (VILI) models with adult rats, macrophages were 
reported to mediate disruption of epithelial barrier function and edema (Frank et al. 2006; Eyal et 
al. 2007). Interestingly, in the RILF model, macrophages represented the most enriched cell type 
induced by radiation damage, which were subsequently normalized by therapeutic pamrevlumab 
administration (Bickelhaupt et al. 2017; Sternlicht et al. 2018). Together, these data suggest that 
CTGF may mediate some aspects of ventilator-induced lung damage and that pamrevlumab may 
attenuate some of the damage. 
Hyperoxia may also contribute to acute lung injury in intubated ARDS patients (Schwarz 2001). 
In the rat neonatal hyperoxia model of bronchopulmonary dysplasia, an antibody with activity 
similar to that of pamrevlumab was able to improve lung development in non-ventilated pups 
(Alapati et al. 2011). This suggests that pamrevlumab might attenuate some of the pathology 
associated with hyperoxia. 
Pathophysiology resulting from SARS-Cov-2 may lead to interstitial lung fibrosis in patients that 
survive the infection. Data from a retrospective cohort study in Wuhan, China (Zhou F Lancet 
2020) show that more than one-third of COVID-19 patients surviving pneumonia have residual 
respiratory failure, due to fibrotic changes in the lung. Approximately 15-30% of patients 
hospitalized for COVID-19 develop acute respiratory distress syndrome (ARDS) (Wang et al. 
2020; Chen et al. 2020; Huang et al. 2020). Patients that survive ARDS often develop fibrosis 


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within 3-4 weeks (Zapol et al. 1979), and the onset of fibrotic changes can begin as early as 36 
hours after lung injury (Schwarz 2001). The distribution and composition of extracellular matrix 
(ECM) within the alveolar wall is similar in both ARDS and idiopathic pulmonary fibrosis (IPF) 
(Raghu et al. 1985), suggesting that pamrevlumab, which has demonstrated antifibrotic effects in 
IPF patients (Raghu et al. 2016; Richeldi et al. 2020), might help in reducing residual fibrotic 
damage in lungs of patients with COVID-19. 
CTGF is a key mediator of pro-fibrotic pathways that has a very complicated biology 
(Lipson et al. 2012). Considered together, the data above suggest that its inhibition might 
mitigate interstitial fibrosis in the post-acute infection setting via multiple mechanisms. In 
addition, it might attenuate edema acutely associated with ARDS and VILI, which may improve 
gas exchange. 
This clinical study has been prepared based on these rationales to address the current medical 
emergency, given the extremely high number of patients affected by COVID-19 disease. 
 
2.3. 
Summary of Past Clinical Studies, Safety and Dosing Information 
The clinical trial experience with pamrevlumab includes 11 completed clinical studies to date. A 
total of 624 subjects have received investigational drug and/or standard of care in these clinical 
trials, including 270 subjects with IPF, 112 subjects with pancreatic cancer, 21 pediatric subjects 
with DMD, 112 subjects with liver fibrosis secondary to hepatitis B, 107 subjects with DN, and 2 
pediatric subjects with focal segmental glomerulosclerosis (FSGS). Approximately 530 subjects 
have received pamrevlumab across these clinical trials. There are studies currently ongoing in 
patients with IPF, pancreatic cancer, and DMD. 
Adverse events (AEs) have been generally mild or moderate in severity and transient in duration. 
The AEs have been typical of the patients’ 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. There is no apparent pattern to the 
serious adverse events (SAEs) observed during clinical trials. 
In a placebo-controlled Phase 2 IPF study of approximately 100 patients, pamrevlumab was well 
tolerated, with a safety profile similar to that of placebo. The placebo group reported more 
TEAEs of cough (43%) than in the pamrevlumab group (28%). 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., and fewer patients in the 
pamrevlumab group (5 [10%]) compared to placebo (7 [13%]) were hospitalized following a 
respiratory-related TESAE. Nine patients died during the study: three (6%) in the pamrevlumab 
group and sic (11%) in the placebo group. 
A Phase 2 dose-response study of pamrevlumab was performed in pancreatic cancer patients 
(Picozzi et al. (2017) J Clin Cancer Trials 2:1). In this study, pamrevlumab (FG-3019) was 
administered every two weeks at doses up to 45 mg/kg, or weekly at 22.5 mg/kg after a loading 
dose of 45 mg/kg. Patients that had trough plasma levels of pamrevlumab immediately before 
the second dose that was greater than 150 µg/ml exhibited better overall survival than those 
whose plasma trough levels were less than 150 µg/ml. Patients that had ascites exhibited lower 
plasma levels of pamrevlumab than patients without ascites. This may be because ascites fluid 


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contains significant amounts of CTGF (data on file), and therefore may act as a sink for 
administered antibody. Patients with ascites that achieved high trough levels of pamrevlumab 
(>150 µg/ml) had a median overall survival that was about 4 times longer than those that had 
lower trough levels (8.7 vs. 1.9 months). Together, these data suggest that it is important to 
achieve high plasma exposure to pamrevlumab in order to achieve maximal benefit. 
In a Phase 2 open label, study, randomized study in locally advanced unresctable pancreatic 
cancer LAPC), patients received 35mg/kg on days 1, 7 and 14 and then after every two weeks for 
total of six month in combination with gemcitabine and paclitaxel vs. combination of 
gemcitabine and paclitaxel. No safety concerns were seen with this dosing regimen and a phase 
3 study in LAPC is ongoing. 
In an open label study in patients age 12 and above with non-ambulatory Duchenne Muscular 
Dystrophy (DMD), pamrevlumab has been administered at 35mg/kg, every 2 weeks, for nearly 
two years with no safety concerns identified. Considered together, the data suggest that three 
weekly doses of pamrevlumab at 35 mg/kg, followed by bi-weekly administration for several 
more months should be well tolerated. 
Supporting the dosing regimen of 35 mg/kg, dosed weekly until Day 14, followed by every 2 
weeks for the remaining treatment period, are data from the PRAISE clinical trial. PRAISE was 
a phase 2 placebo-controlled study in IPF with administration of pamrevlumab once every three 
weeks at 30 mg/kg, for 48 weeks. In PRAISE, the rate of FVC loss in the pamrevlumab-treated 
group was indistinguishable from that of placebo for the first 12 weeks, after which the rate of 
loss in the pamrevlumab-treated subjects was significantly slower (Richeldi et al, 2019). This 
observation suggests that adequate exposure to pamrevlumab to manifest its activity in IPF 
patients was not achieved until about the 4th or 5th dose when it was administered at 30 mg/kg 
every 3 weeks. Repeat dose pharmacokinetic (PK) data in non-human primates indicates that 
achievement of steady-state levels of circulating pamrevlumab requires multiples doses, and that 
this is achieved faster at higher and more frequent doses. Computer modeling of pamrevlumab 
PK in humans also suggests that addition of at least one “loading dose” will result in more rapid 
achievement of efficacious plasma levels. This is the reason for the proposed dosing regimen in 
this acute-care setting. 
Over the course of the entire study, there were numerically more subjects with a HAHA response 
in the pamrevlumab group than in the placebo group. During the main study randomized 
treatment period, 2 subjects in the placebo group had a sample that was both specific and 
reactive for antibodies to pamrevlumab. In the open-label extended treatment period, 7 subjects 
had samples that were specific and reactive: 2 subjects who were randomized to receive 
pamrevlumab and 5 subjects that were randomized to receiving placebo. In a sub-study, 
2 subjects had specific and reactive samples, 1 subject in the pamrevlumab/pirfenidone group 
and 1 subject in the pamrevlumab/nintedanib group. 
Overall, incidence of apparent HAHA within the group was low and the signal was detected at a 
low titer. Therefore FibroGen believes that these HAHA responses are most likely due to non- 
specific assay variability. However, FibroGen will continue to assess the impact of 
immunogenicity and neutralizing antibody (if any) in future studies. 


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In summary, pamrevlumab has been shown to be well tolerated. For additional information on 
the safety of pamrevlumab in IPF patients and in other indications, please refer to the current 
version of the Investigator’s Brochure. 
 
2.3.1. 
Clinical efficacy in completed studies: 
Two studies of pamrevlumab in subjects with pancreatic cancer have demonstrated preliminary 
evidence of efficacy as measured by OS and by eligibility for surgical exploration and resection. 
The results of an open-label Phase 2 study and a randomized, placebo-controlled Phase 2 study 
suggests pamrevlumab slows the progression of IPF as measured by change in FVC % predicted, 
quantitative analysis of fibrosis, and time to disease progression or death. (King 2009; Raghu et 
al, 2004; Zisman et al, 2010; King et al, 2014; Richeldi et al, 2014; Raghu et al. 2016, Clukers et 
al. 2018; Richeldi et al, 2019). 
 
2.4. 
Ongoing clinical study in patients with SARS-CoV-2 Infection 
An Investigator-Initiated Phase 2/3 open-label, randomized, parallel-arm study investigating the 
efficacy and safety of intravenous administration of pamrevlumab versus standard of care in 
patients with COVID-19 disease due to SARS-CoV-2 infection has recently been initiated in 
Italy: Study FGCL-3019-IST-014. 


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3. 
OBJECTIVES AND ASSESSMENTS 
3.1. 
Objective 
To assess the efficacy and safety of intravenous pamrevlumab, an investigational monoclonal 
antibody against connective-tissue growth factor (CTGF), compared to placebo, in hospitalized 
patients with acute COVID-19 disease due to confirmed SARS-COV-2 infection. 
 
3.2. 
Efficacy Assessments 
Primary Efficacy Endpoint 
Proportion of subjects alive and never received mechanical ventilation at Day 14 
Secondary Efficacy Endpoints 
• Proportion of subjects alive, discharged home, and not on supplemental oxygen at 
Day 28 
• Time to recovery by Day 28 based on 8-point ordinal scale (Day of recovery is 
defined as the first day on which the patient satisfies one of the following three 
categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen; 
2) Not hospitalized (discharged), but with limitation on activities and/or requiring 
home supplemental oxygen; 3) Not hospitalized (discharged), with no limitations on 
activities and not requiring supplemental oxygen 
• Clinical status based on 8-point ordinal scale (time range: Days 1 to 28) 
• Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28 
• Days on mechanical ventilation and/or ECMO at Day 28 
• Time to mechanical ventilation/ECMO or all-cause mortality at Day 28 
• All-cause mortality at Day 28 (proportion of subjects deceased) 
• Time to death from any cause at Day 28 
• Change in PaO2/FiO2 ratio as categorical variable using Berlin criteria for ARDS 
categorization (mild, moderate, severe) (time range: Days 1 to 28) 
• Change in PaO2/FiO2 ratio as continuous variable (time range: Days 1 to 28) 
• Change in resting SpO2 adjusted by FiO2 (time range: Days 1 to 28) 
• Change in (non-invasive) oxygen supplementation requirements (time range: Days 1 
to 28) 
 
3.3. 
Safety Assessments 
Treatment-emergent adverse events (TEAEs); treatment-emergent serious adverse events 
(TESAEs), including hypersensitivity/ anaphylactic reactions; clinical laboratory parameters and 
vital signs. 


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4. 
OVERALL STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled phase 2 study of the efficacy and safety 
of intravenous pamrevlumab, a monoclonal antibody against connective-tissue growth factor 
(CTGF), in hospitalized subjects with acute COVID-19 disease due to SARS-CoV-2 infection. 
Eligible subjects are those with documented SARS-CoV-2 infection, age 40 to 85 years, with 
evidence of respiratory compromise requiring hospital admission. This age range was chosen to 
enhance detection of potential clinical benefits in subjects at highest risk for developing severe 
COVID-19 disease in this proof-of-concept study. 
The total sample size is approximately 130 subjects. Subjects are randomized in a 1:1 ratio, 
according to a pre-determined randomization list from a permuted block design. 
Study drug will be administered as IV infusion on Days 1 (day of randomization), 7, 14 and 28. 
A follow-up by visit will be performed 4 weeks after the last dose. 
All subjects will be treated with standard-of-care according to the judgment of the Investigator. 
All concomitant treatments, including approved and non-approved therapies for COVID-19 
disease, will be collected and recorded (see also Section 6.3). 
Safety will be intensively monitored throughout the study. A detailed overview of collection of 
assessments is provided in Section 6 and Schedule of Assessments (SOA). 
 
4.1. 
Subject ID Assignment 
Subjects that sign consent will be assigned an 8 digit Subject ID number consisting of a four 
digit site number and a 4 digits Subject ID starting with 1xxx. Subject numbering will be 
assigned sequentially as subjects are recruited/screened (e.g., 1001, 1002, and 1003, etc.). 
 
4.2. 
Randomization 
Subjects who meet the eligibility criteria during screening will be randomized in a 1:1 ratio 
(pamrevlumab vs placebo) centrally across all sites. 
Automated randomization and treatment assignments will be performed by an Interactive 
Response System (IXRS or IRT). 
 
4.3. 
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. 
The study blind will be maintained for all parties specified above throughout the study. 
Pamrevlumab and placebo will be identical in appearance, packaging, and labeling in order to 
maintain the study blind. 


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4.3.1. 
Request for Unblinding of Treatment Assignment 
Investigators, study site staff and subjects will remain blinded to treatment assignments until 
study completion and database lock. 
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, and should be 
discussed with the Medical Monitor beforehand, if possible. It is the responsibility of the 
investigator to promptly document and explain any unblinding to the sponsor. 
 
4.4. 
Study Duration 
The Screening Period is up to 2 days prior to randomization, to confirm eligibility. 
The Treatment Period is 28 days. Study drug will be administered as IV infusion on Days 1 (day 
of randomization), 7, 14 and 28. 
The Follow-Up Period is 28 days after the last dose. 
Visits /assessments will occur every day for 28 days, or until hospital discharge, whichever 
occurs earlier. If a subject is discharged prior to Day 14 or Day 28, the subject should return as 
outpatient on Days 14 and/or Day 28, for study drug infusions and assessments. 
Subjects who withdraw from the study early, for any reason, will need to return for an Early 
Study Withdrawal /Termination visit 28 days (+7 Days) after the last infusion and may be 
contacted by phone at Day 14 and 28 to check the subject’s survival status. 
See also Section 6 for additional detail. 


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5. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
5.1. 
Inclusion Criteria 
In order to be eligible for inclusion in this trial, a Subject must meet all of the following: 
1. 
Age 40-85 years 
2. 
Confirmed SARS-CoV-2 infection by a FDA-authorized diagnostic test (e.g., 
polymerase chain reaction [PCR] or other approved assay from any specimen 
source; note: a positive serology/antibody test for SARS-CoV-2 does NOT 
qualify as evidence of acute COVID-19 disease) 
3. 
Respiratory compromise requiring hospitalization for COVID-19 disease as 
evidenced by at least one (or more) of the following criteria: 
a. Interstitial pneumonia on CXR or HRCT (findings of consolidation or ground 
glass opacities), OR 
b. Peripheral capillary oxygen saturation (SpO2) < 94% on room air, OR 
c. Requiring non-invasive supplemental oxygen (e.g., nasal cannula, face mask) 
to maintain SpO2 
4. 
Not requiring mechanical ventilation and/or extracorporeal membrane 
oxygenation (ECMO) use at time of randomization 
5. 
Agrees to not participate in another clinical trial for the treatment of COVID-19 
disease through Day 28 
6. 
Subject (or legally authorized representative) able to understand and sign a 
written informed consent form 
 
5.2. 
Exclusion Criteria 
Subjects will be excluded from this trial if any of the following apply: 
1. Female subjects who are pregnant or nursing 
2. Participation in a clinical trial with another investigational drug for COVID-19 
disease 
3. Anticipated discharge from the hospital or transfer to another hospital or long-term 
care facility which is not a study site within 72 hours of randomization 
4. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies 
 
5.3. 
Study Withdrawal Criteria 
Subjects may withdraw from the study at any time, for any reason. Reasons for discontinuing 
will be documented and Subjects are encouraged to have a final follow-up visit (in person or by 
phone) to check on the general health of the subject. 


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Reasons for withdrawing the Subject from the study include the following: 
• Any safety concern in the Investigator’s opinion, that precludes further study 
participation 
• Female subjects who are pregnant or nursing 
• Participation in a clinical trial with another investigational drug for COVID-19 
disease 
• Withdrawal of Consent 
5.4. 
Replacement of Study Subjects 
All randomized subjects will be included in the study. Subjects who terminate the study early 
will not be replaced. 
 
5.5. 
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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6. 
STUDY ASSESSMENTS 
6.1. 
Laboratory Assessments, including ABG and SpO2 
Labs will be collected locally for safety and include hematology: CBC (complete blood count) 
and differential, chemistry: CMP (Comprehensive Metabolic Panel), and routine coagulation 
panel (INR, PT, aPTT). 
Arterial blood gas (ABG) will be collected each day the patient is in ICU/CCU, and recorded 
anytime if performed as part of routine care outside ICU/CCU, while hospitalized. 
Peripheral capillary oxygen saturation (SpO2) will be collected each day while hospitalized. 
 
6.2. 
Modified WHO Ordinal Scale 
Assessment of clinical status, using an 8-Point, Modified WHO Ordinal Scale as specified 
below, should be assessed daily, until Day 28: 
1. Not hospitalized, no limitations on activities 
2. Not hospitalized, limitations on activities and/or requiring home oxygen 
3. Hospitalized, not requiring supplemental oxygen, no longer requiring medical care 
4. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 
(COVID-19-re;ated or otherwise) 
5. Hospitalized, requiring supplemental oxygen 
6. Hospitalized, requiring nasal high-flow oxygen, non-invasive mechanical ventilation, or 
both 
7. Hospitalized, requiring invasive mechanical ventilation, extra-corporeal membrane 
oxygenation (ECMO), or both 
8. Death 
 
6.3. 
Concomitant Medications, Supplemental Oxygen Needs, and other 
Care 
Subjects will be treated according to best available standard-of-care according to the judgment of 
the Investigator. All concomitant medications, including approved and non-approved treatments 
for COVID-19 (e.g., hydroxychloroquine, IL-6 inhibitors, etc.), as well as supplemental oxygen 
needs, will be collected and recorded. 
In addition, the following will be recorded and collected: documentation of SARS-Cov-2 
infection, documentation of any other infection(s) prior to or during hospitalization, and whether 
or not aggressive care is withheld or withdrawn, including the reason for withholding or 
withdrawal of care (e.g., DNR/DNI order, resource limitation). 


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7. 
STUDY DRUG 
Pamrevlumab is a fully human IgG1 kappa monoclonal antibody that binds to CTGF and is 
formulated as solution for administration by IV infusion. 
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. 
Matching placebo is formulated as solution to be administered in a manner that is identical to 
pamrevlumab infusion. 
 
7.1. 
Study Drug Packaging and Labeling 
Labels will be prepared and will comply with Good Manufacturing Practice requirements for 
labelling and local regulatory guidelines. 
 
7.2. 
Study Drug Storage 
Study drug 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. 
 
7.3. 
Study Drug Preparation 
Study drug is infused undiluted after pooling the contents of the calculated number of vials in an 
empty infusion bag (total volume of fluid must not exceed 410 mL) according to the Dose 
Preparation Instructions in the IP Manual. 
Study drug solutions for infusion must be stored refrigerated (2°C to 8°C) and administered 
within 24 hours of preparation and administered within 6 hours of stored at room temperature. 
Study drug infusion solutions are administered by IV infusion, using an infusion set with a 0.2 
μm in-line filter. 
 
7.4. 
Study Drug Administration 
Dosing will be based on the weight obtained on Day 1. The total dose is not to exceed 4.1g. The 
dose should be prepared in a volume of fluid that does not exceed 410 mL. Study drug will be 
administered as soon as possible after release from the site’s pharmacy and infused within 24 
hours of preparation. Study drug will be administered by IV infusion, using an infusion set with a 
sterile, nonpyrogenic, low-protein-binding in-line filter (0.2-micron pore size). 
The first infusion shall be completed in approximately 2 hours. If the first infusion is well 
tolerated and no infusion related AEs are observed during the infusion or subsequent 1-hour 
observation period, the second infusion shall be completed in approximately 1 hour. The 2 


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subsequent infusion periods may be shortened to approximately 30 minutes if no infusion-related 
AEs were observed. 
If an infusion-related AE occurs during the subsequent infusion, study drug will be administered 
over approximately 1 hour for the next three infusions. If no drug-related AEs are observed in 
any of these three infusions, the duration of infusion may be decreased 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 reaction, the infusion rate may be slowed or temporarily stopped, depending on the 
severity of symptoms. 
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 
reaction. Signs and symptoms should be managed with appropriate standard of care treatment. 
7.5. 
Study Drug Handling and Disposal 
All study drug must be controlled and tracked. Drug accountability and reconciliation for all 
study drug received should be completed by the study site. All used, unused, and partially used 
study drug should be destroyed on site according to local/institutional policies by the 
pharmacy/authorized staff with approval from Sponsor (or designee), and destruction records 
maintained. IV bags used to infuse study drug can be disposed of per institutional policy. 


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8. 
ASSESSMENTS OF SAFETY 
8.1. 
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. 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. 
 
8.2. 
Definitions 
8.2.1. 
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. 
 
8.2.2. 
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 


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• 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 
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. 
 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events 
8.3.1. 
Adverse Event Reporting Period 
The safety reporting period begins after the subject has signed the informed consent and ends 28 
days after the last dose of study drug. 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 8.3.5). Pregnancy reporting requirements are outlined 
in Section 8.3.6. 
Adverse events will be followed until resolved, stable, or until the subject’s last study visit or 
subject is lost to follow-up. 
 
8.3.2. 
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 


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event. The investigator is expected to follow reported adverse events until stabilization or 
reversibility. 
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” 
8.3.3. 
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 v5.0) 
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. 
8.3.4. 
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 


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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. 
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 
 
8.3.5. 
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/assent through 28 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 EOS/safety follow-up visit 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). 
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). 
 
8.3.5.1. 
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 and IRB/EC requirements. 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. 
 
8.3.5.2. 
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 8.3.4. 
If the death occurred within the AE collection and reporting period (signed ICF to 28 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 8.3.5. 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. 
 
8.3.6. 
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 


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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. 
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 
28 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 3 months 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. 
 
8.3.7. 
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. 
 
8.3.8. 
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) 


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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) 
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 
 
8.3.9. 
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 and PFTs. 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. 
 
8.3.9.1. 
Special Reporting Situations 
Special Reporting Situations on FibroGen investigational product Pamrevlumab 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. 


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9. 
STATISTICS 
9.1. 
Sample Size Determination 
The sample size of 65 subjects in each treatment arm will provide about 80% power, at 10% two- 
sided significance level, to detect a 20% difference in the proportion of subjects alive and never 
received mechanical ventilation at Day 14. This assumes that 65% of subjects in the placebo arm 
are alive and never received mechanical ventilation at Day 14 compared to 85% in the 
pamrevlumab group. 
 
9.2. 
Analysis Populations 
Enrollment and disposition summaries will be provided on all randomized subjects. 
The Safety Population consists of all subjects who have received at least one dose of study drug. 
All safety summaries will be based on the Safety Population. 
The Intent-To-Treat Set (ITT) consists of all randomized subjects. All efficacy analyses will be 
performed based on the ITT set. 
 
9.3. 
General Considerations 
Baseline value is defined as mean of all screening and Day 1 values prior to the first dose. 
Descriptive summaries will be presented for study parameters including baseline characteristics, 
safety, and efficacy. 
Continuous variables will be reported in mean, standard deviation or standard error, median, Q1- 
Q3, minimum, and maximum. 
Categorical variables will be reported in frequency and percentage of subjects within each 
outcome category. 
 
9.4. 
Statistical Methods 
The analysis of the proportion of subjects alive and never received mechanical ventilation at Day 
14, the proportion of subjects alive, discharged home, and not on supplemental oxygen at Day 
28, proportion of subjects’ clinical status based on an 8-point ordinal scale, and proportion of 
subjects with categorical PaO2/FiO2 ratio endpoints will be conducted using logistic regression 
model with treatment group and adjusting for relevant baseline prognostic covariates. 
The number of days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 
28, number of days on mechanical ventilation and/or ECMO at Day 28 will be analyzed using 
the analysis of covariance (ANCOVA). 
Change in PaO2/FiO2 ratio to day 28, change in resting SpO2 adjusted by FiO2 to day 28, change 
in (non-invasive) oxygen supplementation requirements to day 28 will be analyzed using Mixed 
Model for Repeated Measures (MMRM) approach using relevant prognostic factors as 
covariates and treatment and Time and treatment *time interaction 


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The analysis will take into account the inter-current events as follows: 
1. Treatment discontinuation (e.g., due to AEs, Withdrawal by Subject or Physician 
Decision): Missing endpoint will be imputed by the last result prior to discontinuation. 
2. Death: Composite strategy: inter-current event is taken to be a component of the variable. 
For number of days not requiring mechanical ventilation at Day 14, number of days in 
ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28, and number 
of days on mechanical ventilation and/or ECMO at Day 28; days with missing data after 
death will be imputed with the worst result until Day 28. 
3. Treatment discontinuation due to recovering and discharged from hospital: Missing 
endpoint will be imputed with the last result prior to discontinuation. 
Treatment comparison analysis of time to event endpoints, will be performed using cox 
regression model adjusting for relevant baseline prognostic factors. Hazard ratios together with 
95% two-sided confidence intervals for the hazard ratio will be provided. 
Time to recovery by Day 28, time to mechanical ventilation/ECMO or all-cause mortality by 
Day 28, and all-cause mortality at Day 28 (proportion of subjects deceased), and time to death 
from any cause at Day 28 will be analyzed using Cox regression adjusting for relevant 
prognostics factors.  Other methods will be used as appropriate. 
 
9.5. 
Safety Analyses 
All subjects who received any dose of pamrevlumab will be included in the safety analyses 
which will summarize treatment-emergent adverse events (TEAEs); treatment-emergent serious 
adverse events (TESAEs); clinical laboratory parameters and vital signs, as well as 
hypersensitivity/anaphylactic reactions. 


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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) and Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
requirements. 
This protocol, the Informed Consent Form, and the Investigator’s Brochure must be approved by 
a properly constituted IRB/IEC before the study is initiated and before any investigational 
product is shipped to the investigator. 
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. 
Prior to participation in any study-specific procedures, the subject (or legally authorized 
representative) must sign an IRB/IEC-approved written Informed Consent Form (ICF) in his/her 
native language. 
 
10.2. 
Communication with the Institutional Review Board or Independent 
Ethics Committee 
This protocol, the Informed Consent Form, the Investigator’s Brochure, 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 re-approval 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 Investigator’s Brochure, 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. 


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10.3. 
Subject Information and Consent 
Prior to participation in any study-specific procedures, the subject must sign (note: all references 
to “subject” in this section refers to the study subject or his/her legally acceptable representative) 
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. 
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 
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 (or legally authorized representative) must provide his or her consent for the use 
and disclosure of personal health information in accordance with applicable regulatory 
requirements. 
 
10.4. 
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 or other disclosure authorization 
documents signed by the subject, unless permitted or required by applicable 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). 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. 
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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13. 
REFERENCES 
 
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Lipson KE, Wong C, Teng Y, et al. (2012) CTGF is a central mediator of tissue remodeling and 
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Muro AF, Moretti FA, Moore BB, et al. (2008) An essential role for fibronectin extra type III 
domain A in pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 
177: (6):638-645 
Neesse, A., K.K. Frese, T.E. Bapiro, T. Nakagawa, M.D. Sternlicht, T.W. Seeley, C. Pilarsky, 
D.I. Jodrell, S.M. Spong, and D.A. Tuveson. 2013. 'CTGF antagonism with mAb FG-3019 
enhances chemotherapy response without increasing drug delivery in murine ductal pancreas 
cancer', Proc. Natl. Acad. Sci U. S. A, 110: 12325-30 
Perbal B (2004) CCN proteins: multifunctional signaling regulators. Lancet 363: (9402):62-64 
Perbal B, Tweedie S, Bruford E. (2018) The official unified nomenclature adopted by the HGNC 
calls for the use of the acronyms, CCN1-6, and discontinuation in the use of CYR61, CTGF, 
NOV and WISP 1-3 respectively. J Cell Commun Signal. 12(4):625-629 
Pi L, Fu C, Lu Y, et al. (2018) Vascular Endothelial Cell-Specific Connective Tissue Growth 
Factor (CTGF) Is Necessary for Development of Chronic Hypoxia-Induced Pulmonary 
Hypertension. Front Physiol. 9:138 
Picozzi VJ, Pipas JM, Koong AC, Giaccia AJ, Bahary N, et al. (2017) FG-3019, A Human 
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idiopathic pulmonary fibrosis. New England Journal of Medicine 363: (7):620-6 


 
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Pamrevlumab 
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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
 
Screening 
Treatment 
4-Weeks 
after Last 
Dose 
Up to 2 days prior to Day 1 
Day 1 
Days 2-66 
Day 7 
Days 8-136 
Day 14 
Days 15-27 6 
Day 28 
Informed consent 
X 
Eligibility criteria 
X 
Medical History 
X 
Demographic information 
X 
Vital signs 
X 
X1 
X 
X1 
X 
X1 
X 
X1 
Urine pregnancy test2 
X 
Concomitant medication and non-drug therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion 
X 
X 
X 
X 
Local laboratory tests (hematology: CBC and 
differential, chemistry: CMP, coagulation 
parameters: INR, PT, aPTT) 
X 
X 
X 
X 
X 
Arterial Blood Gasses (ABG) 5 
X 
X 
X 
X 
X 
X 
X 
X 
Resting SpO2 4 
X 
X 
X 
X 
X 
X 
X 
X 
Oxygen Supplementation Needs3, 4 
X 
X 
X 
X 
X 
X 
X 
X 
WHO Ordinal Scale 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Survival, ICU and Hospital Discharge Status 
X 
X 
X 
X 
X 
X 
X 
X 
 
1 On infusion days, vitals taken within 30 minutes prior and 30 min after infusion; otherwise vitals taken daily 2 Women of child-bearing potential. 
3 Need for mechanical ventilation/ECMO, including ventilator settings, or supplemental oxygen, including mode of oxygen delivery. 4 Collected until Day 28 
or hospital discharge, whichever occurs earlier 5 ABGs are collected daily while in ICU/CCU, and recorded if performed as part of routine care outside of ICU/CCU, until Day 28 or hospital 
discharge, whichever occurs earlier 6 if subject is discharged, these visit do not apply; subject should return for infusion visits only. 
 
 
 
 
 
 
 
 
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CLINICAL STUDY PROTOCOL 
 
STUDY TITLE: 
Randomized, Double-Blind, Placebo-Controlled 
Phase 2 Study of the Efficacy and Safety of 
Intravenous Pamrevlumab, a Monoclonal Antibody 
Against Connective Tissue Growth Factor (CTGF), 
in Hospitalized Patients with Acute COVID-19 
Disease 
 
PROTOCOL NUMBER: 
FGCL-3019-098 
 
PHASE: 
Phase 2 
 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
 
KEY SPONSOR CONTACTS: 
Name: 
 
Title: 
 
Telephone: 
 
Mobile: 
 
E-mail Address: 
 
Name: 
 
Title: 
 
Telephone: 
 
Mobile: 
 
E-mail Address: 
 
IND NUMBER: 
149628 
 
STUDY DRUG: 
Pamrevlumab (FG-3019) 
 
INDICATION: 
Hospitalized patients with acute COVID-19 disease 
due to confirmed SARS-CoV-2 infection 
ORIGINAL PROTOCOL: 
01 May 2020 
AMEDMENT 1.0: 
12 May 2020 
 
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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INVESTIGATOR SIGNATURE PAGE 
STUDY ACKNOWLEDGEMENT 
 
Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Efficacy and Safety of 
Intravenous Pamrevlumab, a Monoclonal Antibody Against Connective Tissue Growth Factor 
(CTGF), in Hospitalized Patients with Acute COVID-19 Disease 
FGCL-3019-098 
 
Original: 01 May 2020 
Amendment 1.0: 12 May 2020 
 
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 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. 


D o c u Si g n  E n v el o p e  I D: 0 1 5 3 A 1 E F -5 6 1 F -4 6 F 9 -A 5 1 B -3 5 C 1 F 6 C B C 9 7 B  
Pa mre vl u ma b  
F G C L -3 0 1 9 -0 9 8  
C o nfi de ntial  
Pa ge  3  of  4 1  
Pa ge  3  of  8 4  
 
 
2  
C O N FI R M A TI O N  O F  P R O T O C O L  A P P R O V A L  
Ori gi nal Pr ot oc ol Date:  0 1  Ma y  2 0 2 0 
A me n d me nt 1. 0: 1 2 Ma y 2 0 2 0 
T his  pr ot oc ol is a p pr o ve d b y Fi br o Ge n. 
 
 
 
 
 
 
 
4 5 : 2 9  P D T  
 
 
 
 
 
Fi br o Ge n, I n c. 
 
Date  
 
 
2 3 - M a y - 2 0  I  1 6
 
 


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AMENDMENT 1.0: KEY CHANGES FROM ORIGINAL PROTOCOL 
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 Endpoint updated to 
include proportion of subjects who 
never received mechanical 
ventilation and/or ECMO and are 
alive at Day 28 
Per FDA feedback modified the time 
point of the primary endpoint to ensure 
a sufficient number of events will occur 
Synopsis, 
Sections 3.2, 
9.1, and 9.4 
Secondary Endpoint added to 
include proportion of subjects who 
never received mechanical 
ventilation and/or ECMO and are 
alive at Day 14 
Added additional secondary endpoint 
to further assess events at Day 14 
Synopsis and 
Sections 3.2 
and 9.4 
Subjects who do not receive all 
study drug doses, will be 
encouraged to continue with all 
study visits and assessments 
Per FDA feedback, updated to collect 
data on all comers and to prevent 
missing data 
Section 4.4 and 
5.3 
Added distinction between 
Treatment Discontinuation and 
Study Withdrawal, and clarified 
that subjects who discontinue 
treatment are encouraged to 
remain on study. Specified 
mandatory reasons for study 
withdrawal 
Per FDA feedback, updated to ensure 
lost to follow-up is a specific reason for 
withdraw and clarified withdraw 
treatment criteria. 
Section 5.3 
Clarify that vital status can be 
obtained from public records 
Per FDA feedback, add to support the 
collection of data and to prevent 
missing data 
Section 6.3 
Clarify that all new or worsened 
lab abnormalities should be 
reported as adverse events 
Per FDA feedback, updated language 
to clarify that lab abnormalities will be 
recorded as AEs 
Section 8.3.7 
Added Data Monitoring 
Committee (DMC) 
Per FDA feedback, added that a DMC 
will be utilized 
Section 8.3.9.2 


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Added Interim Safety Analysis as 
part of the DMC Responsibilities 
Per FDA feedback, an interim analysis 
for safety is added as part of the DMC 
responsibilities 
Section 8.3.9.2 
Added that visits can be conducted 
remotely 
Per FDA, to maximize data collection 
allow for remote visits 
Section 5.3, 
Schedule of 
Assessments 


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1. 
PROTOCOL SYNOPSIS 
 
 
PROTOCOL SYNOPSIS 
Study Title: 
Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of 
the Efficacy and Safety of Intravenous Pamrevlumab, a 
Monoclonal Antibody Against Connective Tissue Growth Factor 
(CTGF), in Hospitalized Patients with Acute COVID-19 Disease 
Protocol Number: 
FGCL-3019-098 
Investigational Product: 
Pamrevlumab (FG-3019) 
Study Phase: 
Phase 2 
Indication: 
Hospitalized patients with acute COVID-19 disease due to 
confirmed SARS-COV-2 infection 
Number of 
Subjects Planned: 
Approximately 130 
Number of Sites Planned: 
Approximately 5-10 in the USA 
OBJECTIVES 
To assess the efficacy and safety of pamrevlumab, an investigational monoclonal antibody against 
connective tissue growth factor (CTGF), compared to placebo, in hospitalized patients with acute 
COVID-19 disease due to confirmed SARS-COV-2 infection. 


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Endpoints 
Efficacy Assessments: 
Primary Efficacy Endpoint 
Proportion of subjects who never received mechanical ventilation and/or ECMO and alive at Day 
28 
Secondary Efficacy Endpoints 
• Proportion of subjects alive, discharged home, and not on supplemental oxygen at Day 28 
• Proportion of subjects who never received mechanical ventilation and/or ECMO and alive 
at Day 14 
• Time to recovery by Day 28 based on 8-point ordinal scale (Day of recovery is defined as 
the first day on which the patient satisfies one of the following three categories from the 
ordinal scale: 1) Hospitalized, not requiring supplemental oxygen; 2) Not hospitalized 
(discharged), but with limitation on activities and/or requiring home supplemental oxygen; 
3) Not hospitalized (discharged), with no limitations on activities and not requiring 
supplemental oxygen 
• Clinical status based on 8-point ordinal scale (time range: Days 1 to 28) 
• Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28 
• Days on mechanical ventilation and/or ECMO at Day 28 
• Time to mechanical ventilation/ECMO or all-cause mortality at Day 28 
• All-cause mortality at Day 28 (proportion of subjects deceased) 
• Time to death from any cause at Day 28 
• Change in PaO2/FiO2 ratio as categorical variable using Berlin criteria for ARDS 
categorization (mild, moderate, severe) (time range: Days 1 to 28) 
• Change in PaO2/FiO2 ratio as continuous variable (time range: Days 1 to 28) 
• Change in resting SpO2 adjusted by FiO2 (time range: Days 1 to 28) 
• Change in (non-invasive) oxygen supplementation requirements (time range: Days 1 to 28) 
Safety Assessments: 
Treatment-emergent adverse events (TEAEs); treatment-emergent serious adverse events 
(TESAEs), including hypersensitivity/ anaphylactic reactions; clinical laboratory parameters and 
vital signs. 
STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled phase 2 study to evaluate the efficacy and 
safety of intravenous pamrevlumab, a monoclonal antibody against connective-tissue growth 
factor (CTGF), in hospitalized subjects with acute COVID-19 disease. 
Eligible subjects are those with documented SARS-CoV-2 infection, age 40 to 85 years, with 
evidence of respiratory compromise requiring hospital admission. This age range was chosen to 
enhance detection of potential clinical benefits in subjects at highest risk for developing severe 
COVID-19 disease in this proof-of-concept study. 
Approximately 130 subjects will be randomized in a 1:1 ratio to either pamrevlumab or placebo; 
all subjects will also receive standard-of-care in the judgment of the Investigator. 
Study drug administration is via IV infusion on Days 1 (day of randomization), 7, 14 and 28. A 
follow-up by visit will be performed 4 weeks after the last dose. 


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All concomitant medications, including approved and non-approved treatments for COVID-19 
(e.g., hydroxychloroquine, IL-6 inhibitors, etc.), as well as supplemental oxygenation needs, will 
be collected and recorded. In addition, the following will be collected and recorded: documentation 
of SARS-Cov-2 infection, documentation of any other infection(s) prior to or during 
hospitalization, and whether or not aggressive care is withheld or withdrawn, including the reason 
for withholding or withdrawal of care (e.g., DNR/DNI order, resource limitation). 
STUDY PERIODS 
Screening Period: Up to 2 days prior to randomization 
Treatment Period: 28 days 
Follow-Up Period: 28 days after last dose 
SUBJECT ELIGIBILITY CRITERIA 
Inclusion Criteria: 
1. Age 40-85 years 
2. Confirmed SARS-CoV-2 infection by a FDA-authorized diagnostic test (e.g., polymerase 
chain reaction [PCR] or other approved assay from any specimen source; note: a positive 
serology/antibody test for SARS-CoV-2 does NOT qualify as evidence of acute COVID- 
19 disease) 
3. Respiratory compromise requiring hospitalization for COVID-19 disease as evidenced by 
at least one (or more) of the following criteria: 
a. Interstitial pneumonia on CXR or HRCT (findings of consolidation or ground glass 
opacities), OR 
b. Peripheral capillary oxygen saturation (SpO2) < 94% on room air, OR 
c. Requiring non-invasive supplemental oxygen (e.g., nasal cannula, face mask) to 
maintain SpO2 
4. Not requiring mechanical ventilation and/or extracorporeal membrane oxygenation 
(ECMO) use at time of randomization 
5. Agrees to not participate in another clinical trial for the treatment of COVID-19 disease 
through Day 28 
6. Subject (or legally authorized representative) able to understand and sign a written 
informed consent form 


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Exclusion Criteria: 
1. Female subjects who are pregnant or nursing 
2. Participation in a clinical trial with another investigational drug for COVID-19 disease 
3. Anticipated discharge from the hospital or transfer to another hospital or long-term care 
facility which is not a study site within 72 hours of randomization 
4. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies 
STUDY TREATMENT 
Dose and mode of administration 
Dose: 35 mg/kg IV 
Dosing regimen: Days 1, 7, 14 and 28. 
Other important information 
Study drug should not be administered to subjects with a history of allergic or anaphylactic 
reaction to human, humanized, or chimeric monoclonal antibodies. 
STATISTICAL METHODS 
Determination of sample size 
The sample size of 65 subjects in each treatment arm will provide approximately 80% power, at 
10% two-sided significance level, to detect a 20% absolute difference in the proportion of subjects 
who never received mechanical ventilation / ECMO and are alive at Day 28. This assumes that 
65% of subjects in the placebo arm that never received mechanical ventilation / ECMO and are 
alive at Day 28, compared to 85% in the pamrevlumab group. 
Randomization 
Subjects who meet all eligibility criteria during screening will be randomized in a 1:1 ratio 
(pamrevlumab vs placebo) centrally across all sites and based on a pre-determined randomization 
list from a permuted block design. 
Statistical analysis methods 
The analysis of the proportion of subjects who never received mechanical ventilation and/or ECMO 
and alive at Days 14 and Day 28, the proportion of subjects alive, discharged home, and not on 
supplemental oxygen at Day 28, proportion of subjects’ clinical status based on an 8-point ordinal 
scale, and proportion of subjects with categorical PaO2/FiO2 ratio endpoints will be conducted 
using logistic regression model with treatment group and adjusting for relevant baseline prognostic 
covariates. 
The number of days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 
28, number of days on mechanical ventilation and/or ECMO at Day 28 will be analyzed using the 
analysis of covariance (ANCOVA). 
Change in PaO2/FiO2 ratio to day 28, change in resting SpO2 adjusted by FiO2 to day 28, change in 
(non-invasive) oxygen supplementation requirements to day 28 will be analyzed using Mixed 


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Model for Repeated Measures (MMRM) approach using relevant prognostic factors as covariates 
and treatment and Time and treatment *time interaction. 
The analysis will take into account the inter-current events as follows. 
1. Treatment discontinuation (e.g., due to AEs, Withdrawal by Subject or Physician 
Decision): Missing endpoint will be imputed by the last result prior to discontinuation. 
2. Death: Composite strategy: inter-current event is taken to be a component of the variable. 
For number of days not requiring mechanical ventilation at Day 14, number of days in 
ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28, and number 
of days on mechanical ventilation and/or ECMO at Day 28; days with missing data after 
death will be imputed with the worst result until Day 28. 
3. Treatment discontinuation due to recovering and discharged from hospital: Missing 
endpoint will be imputed with the last result prior to discontinuation. 
Treatment comparison analysis of time to event endpoints, will be performed using cox regression 
model adjusting for relevant baseline prognostic factors. Hazard ratios together with 95% two- 
sided confidence intervals for the hazard ratio will be provided. 
Time to recovery by Day 28, time to mechanical ventilation/ECMO or all-cause mortality by Day 
28, and all-cause mortality at Day 28 (proportion of subjects deceased), and time to death from 
any cause at Day 28 will be analyzed using Cox regression adjusting for relevant prognostics 
factors. Other methods will be used as appropriate. 
Safety analyses 
All subjects who received any dose of pamrevlumab will be included in the safety population 
analyses which will summarize treatment-emergent adverse events (TEAEs); treatment-emergent 
serious adverse events (TESAEs), including hypersensitivity/ anaphylactic reactions; clinical 
laboratory parameters and vital signs. 
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 
1. 
PROTOCOL SYNOPSIS .............................................................................................6 
2. 
INTRODUCTION ......................................................................................................14 
2.1. 
Description of Pamrevlumab ......................................................................................14 
2.2. 
Background Information and Study Rationale ............................................................14 
2.2.1. 
Connective Tissue Growth Factor (CTGF) .................................................................14 
2.2.2. 
Study Rationale ...........................................................................................................14 
2.3. 
Summary of Past Clinical Studies, Safety and Dosing Information ...........................16 
2.3.1. 
Clinical efficacy in completed studies: .......................................................................18 
2.4. 
Ongoing clinical study in patients with SARS-CoV-2 Infection ................................18 
3. 
OBJECTIVES AND ASSESSMENTS ......................................................................18 
3.1. 
Objective .....................................................................................................................18 
3.2. 
Efficacy Assessments .................................................................................................18 
3.3. 
Safety Assessments .....................................................................................................19 
4. 
OVERALL STUDY DESIGN ....................................................................................19 
4.1. 
Subject ID Assignment ...............................................................................................20 
4.2. 
Randomization ............................................................................................................20 
4.3. 
Blinding ......................................................................................................................20 
4.3.1. 
Request for Unblinding of Treatment Assignment .....................................................20 
4.4. 
Study Duration ............................................................................................................20 
5. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................21 
5.1. 
Inclusion Criteria ........................................................................................................21 
5.2. 
Exclusion Criteria .......................................................................................................21 
5.3. 
Early Treatment Termination and Study Withdrawal .................................................22 
5.4. 
Replacement of Study Subjects ..................................................................................22 
5.5. 
Study Closure ..............................................................................................................22 
6. 
STUDY ASSESSMENTS ..........................................................................................23 
6.1. 
Laboratory Assessments, including ABG and SpO2 ..................................................23 
6.2. 
Modified WHO Ordinal Scale ....................................................................................23 
6.3. 
Concomitant Medications, Supplemental Oxygen Needs, and other Care .................23 
7. 
STUDY DRUG ...........................................................................................................24 
7.1. 
Study Drug Packaging and Labeling ..........................................................................24 


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7.2. 
Study Drug Storage .....................................................................................................24 
7.3. 
Study Drug Preparation...............................................................................................24 
7.4. 
Study Drug Administration. ........................................................................................24 
7.5. 
Study Drug Handling and Disposal ............................................................................25 
8. 
ASSESSMENTS OF SAFETY ..................................................................................25 
8.1. 
Background .................................................................................................................25 
8.2. 
Definitions ................................................................................................................. 25 
8.2.1. 
Definition of an Adverse Event (AE) .........................................................................25 
8.2.2. 
Definition of a Serious Adverse Event (SAE) ............................................................26 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events .........................26 
8.3.1. 
Adverse Event Reporting Period ................................................................................26 
8.3.2. 
Adverse Event Eliciting/Reporting .............................................................................27 
8.3.3. 
Assessing Adverse Event Severity .............................................................................27 
8.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug ......................................28 
8.3.5. 
Reporting Serious Adverse Events (SAEs) .................................................................29 
8.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review Board / 
Independent Ethics Committee ...................................................................................29 
8.3.5.2. 
Deaths .........................................................................................................................29 
8.3.6. 
Pregnancies: Reporting and Follow-up of Subjects and Female Partners of 
Subjects .......................................................................................................................30 
8.3.7. 
Laboratory or other Test Abnormalities/ Findings .....................................................30 
8.3.8. 
Hypersensitivity/Anaphylactic Reactions: ..................................................................30 
8.3.9. 
Safety Monitoring .......................................................................................................31 
8.3.9.1. 
Special Reporting Situations .......................................................................................31 
8.3.9.2. 
Data Monitoring Committee (DMC) ......................................................................... 31 
9. 
STATISTICS ..............................................................................................................32 
9.1. 
Sample Size Determination ........................................................................................32 
9.2. 
Analysis Populations.................................................................................................. 32 
9.3. 
General Considerations ...............................................................................................32 
9.4. 
Statistical Methods ......................................................................................................32 
9.5. 
Safety Analyses...........................................................................................................33 
10. 
ETHICS ......................................................................................................................33 
10.1. 
Ethical Considerations ................................................................................................33 


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10.2. 
Communication with the Institutional Review Board or Independent Ethics 
Committee ...................................................................................................................34 
10.3. 
Subject Information and Consent ...............................................................................34 
10.4. 
Confidentiality ............................................................................................................35 
11. 
DATA HANDLING AND RECORD KEEPING ......................................................35 
11.1. 
Source Documents ......................................................................................................35 
11.2. 
Direct Access to Source Documents ...........................................................................35 
11.3. 
Data Collection, Handling, and Verification ..............................................................35 
11.4. 
Protocol Deviations .................................................................................................... 36 
11.5. 
Retention of Data ........................................................................................................36 
11.6. 
Financial Disclosure ...................................................................................................36 
12. 
PUBLICATION POLICY ..........................................................................................36 
13. 
REFERENCES ...........................................................................................................38 
APPENDIX 1: SCHEDULE OF ASSESSMENTS .......................................................................41 


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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 (e.g, 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.
Background Information and Study Rationale
2.2.1.
Connective Tissue Growth Factor (CTGF)
CTGF is a 38 kDa secreted matricellular glycoprotein of the cysteine-rich
61/CTGF/nephroblastoma overexpression family (Perbal, 2004, Rachfal, 2005) which was
recently renamed cellular communication network (CCN) family (Perbal 2018). It is produced by
many cells, including fibroblasts, myofibroblasts, endothelial cells, mesangial cells, and stellate
cells.
CTGF is a central mediator of tissue remodeling and fibrosis (Lipson, 2012). CTGF is essential
for the fibrotic activity of TGF-B (Mori, 1999, Wang, 2011) but it may also act independently of
TGF-B. While much has been made of the role of TGF-B in fibrosis, studies of the role of
fibronectin in pulmonary fibrosis showed that the activity of TGF-B is dependent on cellular
fibronectin to induce myofibroblast differentiation and that cellular fibronectin may have a
fundamental role in activation of latent TGF-B (Muro, 2008). Shi-wen and colleagues showed
that critical activities of TGF-B 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-B (Shi-wen, 2006).
CTGF has been shown to be an important mediator of pulmonary fibrosis in a mouse model of
bleomycin-induced pulmonary fibrosis (
, 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).
2.2.2.
Study Rationale
Recent data indicate the presence of interstitial pneumonia (consolidation or ground glass
opacities) in a subset of patients infected with novel coronavirus SARS-CoV-2 requiring
hospitalization. The interstitial pneumonia is usually bilateral and responsible for reduced
efficiency of gas exchange, potentially leading to respiratory failure, intubation and finally death
in a significant proportion of patients requiring mechanical ventilation. CTGF (connective tissue
growth factor; CCN2) may promote vascular leakage, and administration of pamrevlumab, an
investigational anti-CTGF monoclonal antibody, can reverse edema. Using the Miles assay,
CTGF promoted vascular leakage in skin (Data on file, generated by FibroGen). In rodent
models of complications of diabetes, the abundance of CTGF in urine correlated to the extent of


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albuminuria (Roestenberg et al. 2006; FibroGen Report 200_04_3050_034). Pamrevlumab was 
shown to inhibit vascular leakage in the lungs after irradiation (Bickelhaupt et al. 2017), and in 
several organs in complications of diabetes models (data on file at FibroGen), as well as to 
suppress ascites in a genetically engineered model of pancreatic cancer (Neesse et al. 2013). 
These observations suggest that administration of pamrevlumab may attenuate edema associated 
with the virus-induced pneumonia and improve gas exchange. 
In addition, published data in several animal models (Pi et al. 2018; Bickelhaupt et al. 2017; 
Sternlicht et al. 2018; Makino et al. 2017; Booth et al. 2010) indicate that pamrevlumab alters 
trafficking of certain immune-related cells. In a mouse radiation-induced lung fibrosis (RILF) 
model, the mechanism by which pamrevlumab-treated mice experienced a rapid reversal of 
pneumonitis appears to be deactivation of myofibroblasts resulting in decreased secretion of 
inflammatory chemokines (Sternlicht et al. 2018). This hypothesis remains to be confirmed for 
the RILF model, and the mechanism(s) by which pamrevlumab alters immune cell trafficking 
remains to be determined. It should also be noted that none of these models involved active viral 
infections, so it is unclear if pamrevlumab would broadly affect inflammation associated with 
SARS-Cov-2 infection resulting in COVID-19 disease. However, if blocking CTGF attenuates 
inflammation, pamrevlumab might reduce symptoms associated with the virus-induced cytokine 
storm. 
In addition to lung damage caused by the immune system’s hyperactive attempt to eradicate the 
viral infection, invasive mechanical ventilation of ARDS patients may also contribute to 
development of pulmonary fibrosis (Cabrera-Benitez et al. 2014). In ARDS patients that 
developed fibrosis, there was a statistically significant correlation between ventilator settings and 
the abundance of TGFB and CTGF in serum (Xie et al. 2019). CTGF has been shown to be 
elevated in ventilated pre-term sheep, and to increase with gas volume (Wallace et al. 2009) and 
flow (Bach et al. 2008). CTGF expression also increases with tidal volume in neonatal rats (Wu 
et al. 2008). In ventilator-induced lung injury (VILI) models with adult rats, macrophages were 
reported to mediate disruption of epithelial barrier function and edema (Frank et al. 2006; Eyal et 
al. 2007). Interestingly, in the RILF model, macrophages represented the most enriched cell type 
induced by radiation damage, which were subsequently normalized by therapeutic pamrevlumab 
administration (Bickelhaupt et al. 2017; Sternlicht et al. 2018). Together, these data suggest that 
CTGF may mediate some aspects of ventilator-induced lung damage and that pamrevlumab may 
attenuate some of the damage. 
Hyperoxia may also contribute to acute lung injury in intubated ARDS patients (Schwarz 2001). 
In the rat neonatal hyperoxia model of bronchopulmonary dysplasia, an antibody with activity 
similar to that of pamrevlumab was able to improve lung development in non-ventilated pups 
(Alapati et al. 2011). This suggests that pamrevlumab might attenuate some of the pathology 
associated with hyperoxia. 
Pathophysiology resulting from SARS-Cov-2 may lead to interstitial lung fibrosis in patients that 
survive the infection. Data from a retrospective cohort study in Wuhan, China (Zhou F Lancet 
2020; 395: 1054) show that more than one-third of COVID-19 patients surviving pneumonia 
have residual respiratory failure, due to fibrotic changes in the lung. Approximately 15-30% of 
patients hospitalized for COVID-19 develop acute respiratory distress syndrome (ARDS) (Wang 
et al. 2020; Chen et al. 2020; Huang et al. 2020). Patients that survive ARDS often develop 


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fibrosis within 3-4 weeks (Zapol et al. 1979), and the onset of fibrotic changes can begin as early 
as 36 hours after lung injury (Schwarz 2001). The distribution and composition of extracellular 
matrix (ECM) within the alveolar wall is similar in both ARDS and idiopathic pulmonary 
fibrosis (IPF) (Raghu et al. 1985), suggesting that pamrevlumab, which has demonstrated 
antifibrotic effects in IPF patients (Raghu et al. 2016; Richeldi et al. 2020), might help in 
reducing residual fibrotic damage in lungs of patients with COVID-19. 
CTGF is a key mediator of pro-fibrotic pathways that has a very complicated biology (Lipson et 
al. 2012). Considered together, the data above suggest that its inhibition might mitigate 
interstitial fibrosis in the post-acute infection setting via multiple mechanisms. In addition, it 
might attenuate edema acutely associated with ARDS and VILI, which may improve gas 
exchange. 
This clinical study has been prepared based on these rationales to address the current medical 
emergency, given the extremely high number of patients affected by COVID-19 disease. 
 
2.3. 
Summary of Past Clinical Studies, Safety and Dosing Information 
The clinical trial experience with pamrevlumab includes 11 completed clinical studies to date. A 
total of 624 subjects have received investigational drug and/or standard of care in these clinical 
trials, including 270 subjects with IPF, 112 subjects with pancreatic cancer, 21 pediatric subjects 
with DMD, 112 subjects with liver fibrosis secondary to hepatitis B, 107 subjects with DN, and 2 
pediatric subjects with focal segmental glomerulosclerosis (FSGS). Approximately 530 subjects 
have received pamrevlumab across these clinical trials. There are studies currently ongoing in 
patients with IPF, pancreatic cancer, and DMD. 
Adverse events (AEs) have been generally mild or moderate in severity and transient in duration. 
The AEs have been typical of the patients’ 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. There is no apparent pattern to the 
serious adverse events (SAEs) observed during clinical trials. 
In a placebo-controlled Phase 2 IPF study of approximately 100 patients, pamrevlumab was well 
tolerated, with a safety profile similar to that of placebo. The placebo group reported more 
TEAEs of cough (43%) than in the pamrevlumab group (28%). 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., and fewer patients in the 
pamrevlumab group (5 [10%]) compared to placebo (7 [13%]) were hospitalized following a 
respiratory-related TESAE. Nine patients died during the study: three (6%) in the pamrevlumab 
group and sic (11%) in the placebo group. 
A Phase 2 dose-response study of pamrevlumab was performed in pancreatic cancer patients 
(Picozzi et al. (2017) J Clin Cancer Trials 2:1). In this study, pamrevlumab (FG-3019) was 
administered every two weeks at doses up to 45 mg/kg, or weekly at 22.5 mg/kg after a loading 
dose of 45 mg/kg. Patients that had trough plasma levels of pamrevlumab immediately before 
the second dose that was greater than 150 µg/ml exhibited better overall survival than those 
whose plasma trough levels were less than 150 µg/ml. Patients that had ascites exhibited lower 
plasma levels of pamrevlumab than patients without ascites. This may be because ascites fluid 


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contains significant amounts of CTGF (data on file), and therefore may act as a sink for 
administered antibody. Patients with ascites that achieved high trough levels of pamrevlumab 
(>150 µg/ml) had a median overall survival that was about 4 times longer than those that had 
lower trough levels (8.7 vs. 1.9 months). Together, these data suggest that it is important to 
achieve high plasma exposure to pamrevlumab in order to achieve maximal benefit. 
In a Phase 2 open label, study, randomized study in locally advanced unresctable pancreatic 
cancer LAPC), patients received 35mg/kg on days 1, 7 and 14 and then after every two weeks for 
total of six month in combination with gemcitabine and paclitaxel vs. combination of 
gemcitabine and paclitaxel. No safety concerns were seen with this dosing regimen and a phase 
3 study in LAPC is ongoing. 
In an open label study in patients age 12 and above with non-ambulatory Duchenne Muscular 
Dystrophy (DMD), pamrevlumab has been administered at 35mg/kg, every 2 weeks, for nearly 
two years with no safety concerns identified. Considered together, the data suggest that three 
weekly doses of pamrevlumab at 35 mg/kg, followed by bi-weekly administration for several 
more months should be well tolerated. 
Supporting the dosing regimen of 35 mg/kg, dosed weekly until Day 14, followed by every 2 
weeks for the remaining treatment period, are data from the PRAISE clinical trial. PRAISE was 
a phase 2 placebo-controlled study in IPF with administration of pamrevlumab once every three 
weeks at 30 mg/kg, for 48 weeks. In PRAISE, the rate of FVC loss in the pamrevlumab-treated 
group was indistinguishable from that of placebo for the first 12 weeks, after which the rate of 
loss in the pamrevlumab-treated subjects was significantly slower (Richeldi et al, 2019). This 
observation suggests that adequate exposure to pamrevlumab to manifest its activity in IPF 
patients was not achieved until about the 4th or 5th dose when it was administered at 30 mg/kg 
every 3 weeks. Repeat dose pharmacokinetic (PK) data in non-human primates indicates that 
achievement of steady-state levels of circulating pamrevlumab requires multiples doses, and that 
this is achieved faster at higher and more frequent doses. Computer modeling of pamrevlumab 
PK in humans also suggests that addition of at least one “loading dose” will result in more rapid 
achievement of efficacious plasma levels. This is the reason for the proposed dosing regimen in 
this acute-care setting. 
Over the course of the entire study, there were numerically more subjects with a HAHA response 
in the pamrevlumab group than in the placebo group. During the main study randomized 
treatment period, 2 subjects in the placebo group had a sample that was both specific and 
reactive for antibodies to pamrevlumab. In the open-label extended treatment period, 7 subjects 
had samples that were specific and reactive: 2 subjects who were randomized to receive 
pamrevlumab and 5 subjects that were randomized to receiving placebo. In a sub-study, 
2 subjects had specific and reactive samples, 1 subject in the pamrevlumab/pirfenidone group 
and 1 subject in the pamrevlumab/nintedanib group. 
Overall, incidence of apparent HAHA within the group was low and the signal was detected at a 
low titer. Therefore FibroGen believes that these HAHA responses are most likely due to non- 
specific assay variability. However, FibroGen will continue to assess the impact of 
immunogenicity and neutralizing antibody (if any) in future studies. 


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In summary, pamrevlumab has been shown to be well tolerated. For additional information on 
the safety of pamrevlumab in IPF patients and in other indications, please refer to the current 
version of the Investigator’s Brochure. 
 
2.3.1. 
Clinical efficacy in completed studies: 
Two studies of pamrevlumab in subjects with pancreatic cancer have demonstrated preliminary 
evidence of efficacy as measured by OS and by eligibility for surgical exploration and resection. 
The results of an open-label Phase 2 study and a randomized, placebo-controlled Phase 2 study 
suggests pamrevlumab slows the progression of IPF as measured by change in FVC % predicted, 
quantitative analysis of fibrosis, and time to disease progression or death. (King 2009; Raghu et 
al, 2004; Zisman et al, 2010; King et al, 2014; Richeldi et al, 2014; Raghu et al. 2016, Clukers et 
al. 2018; Richeldi et al, 2019). 
 
2.4. 
Ongoing clinical study in patients with SARS-CoV-2 Infection 
An Investigator-Initiated Phase 2/3 open-label, randomized, parallel-arm study investigating the 
efficacy and safety of intravenous administration of pamrevlumab versus standard of care in 
patients with COVID-19 disease due to SARS-CoV-2 infection has recently been initiated in 
Italy: Study FGCL-3019-IST-014. 
 
3. 
OBJECTIVES AND ASSESSMENTS 
3.1. 
Objective 
To assess the efficacy and safety of intravenous pamrevlumab, an investigational monoclonal 
antibody against connective-tissue growth factor (CTGF), compared to placebo, in hospitalized 
patients with acute COVID-19 disease due to confirmed SARS-COV-2 infection. 
 
3.2. 
Efficacy Assessments 
Primary Efficacy Endpoint 
Proportion of subjects who never received mechanical ventilation and/or ECMO and alive at Day 
28 
Secondary Efficacy Endpoints 
• Proportion of subjects alive, discharged home, and not on supplemental oxygen at 
Day 28 
• Proportion of subjects who never received mechanical ventilation and/ or ECMO and 
alive at Day 14 
• Time to recovery by Day 28 based on 8-point ordinal scale (Day of recovery is 
defined as the first day on which the patient satisfies one of the following three 
categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen; 
2) Not hospitalized (discharged), but with limitation on activities and/or requiring 


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home supplemental oxygen; 3) Not hospitalized (discharged), with no limitations on 
activities and not requiring supplemental oxygen 
• Clinical status based on 8-point ordinal scale (time range: Days 1 to 28) 
• Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28 
• Days on mechanical ventilation and/or ECMO at Day 28 
• Time to mechanical ventilation/ECMO or all-cause mortality at Day 28 
• All-cause mortality at Day 28 (proportion of subjects deceased) 
• Time to death from any cause at Day 28 
• Change in PaO2/FiO2 ratio as categorical variable using Berlin criteria for ARDS 
categorization (mild, moderate, severe) (time range: Days 1 to 28) 
• Change in PaO2/FiO2 ratio as continuous variable (time range: Days 1 to 28) 
• Change in resting SpO2 adjusted by FiO2 (time range: Days 1 to 28) 
• Change in (non-invasive) oxygen supplementation requirements (time range: Days 1 
to 28) 
 
3.3. 
Safety Assessments 
Treatment-emergent adverse events (TEAEs); treatment-emergent serious adverse events 
(TESAEs), including hypersensitivity/ anaphylactic reactions; clinical laboratory parameters and 
vital signs. 
 
4. 
OVERALL STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled phase 2 study of the efficacy and safety 
of intravenous pamrevlumab, a monoclonal antibody against connective-tissue growth factor 
(CTGF), in hospitalized subjects with acute COVID-19 disease due to SARS-CoV-2 infection. 
Eligible subjects are those with documented SARS-CoV-2 infection, age 40 to 85 years, with 
evidence of respiratory compromise requiring hospital admission. This age range was chosen to 
enhance detection of potential clinical benefits in subjects at highest risk for developing severe 
COVID-19 disease in this proof-of-concept study. 
The total sample size is approximately 130 subjects. Subjects are randomized in a 1:1 ratio, 
according to a pre-determined randomization list from a permuted block design. 
Study drug will be administered as IV infusion on Days 1 (day of randomization), 7, 14 and 28. 
A follow-up by visit will be performed 4 weeks after the last dose. 
All subjects will be treated with standard-of-care according to the judgment of the Investigator. 
All concomitant treatments, including approved and non-approved therapies for COVID-19 
disease, will be collected and recorded (see also Section 6.3). 
Safety will be intensively monitored throughout the study. A detailed overview of collection of 
assessments is provided in Section 6 and Schedule of Assessments (SOA). 


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4.1. 
Subject ID Assignment 
Subjects that sign consent will be assigned an 8 digit Subject ID number consisting of a four 
digit site number and a 4 digits Subject ID starting with 1xxx. Subject numbering will be 
assigned sequentially as subjects are recruited/screened (e.g., 1001, 1002, and 1003, etc.). 
 
4.2. 
Randomization 
Subjects who meet the eligibility criteria during screening will be randomized in a 1:1 ratio 
(pamrevlumab vs placebo) centrally across all sites. 
Automated randomization and treatment assignments will be performed by an Interactive 
Response System (IXRS or IRT). 
 
4.3. 
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. 
The study blind will be maintained for all parties specified above throughout the study. 
Pamrevlumab and placebo will be identical in appearance, packaging, and labeling in order to 
maintain the study blind. 
 
4.3.1. 
Request for Unblinding of Treatment Assignment 
Investigators, study site staff and subjects will remain blinded to treatment assignments until 
study completion and database lock. 
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, and should be 
discussed with the Medical Monitor beforehand, if possible. It is the responsibility of the 
investigator to promptly document and explain any unblinding to the sponsor. 
4.4. 
Study Duration 
The Screening Period is up to 2 days prior to randomization, to confirm eligibility. 
The Treatment Period is 28 days. Study drug will be administered as IV infusion on Days 1 (day 
of randomization), 7, 14 and 28. 
The Follow-Up Period is 28 days after the last dose. 
Visits /assessments will occur every day for 28 days, or until hospital discharge, whichever 
occurs earlier. If a subject is discharged prior to Day 14 or Day 28, the subject should return as 
outpatient on Days 14 and/or Day 28, for study drug infusions and assessments. For subjects who 
cannot return for an in-person visit, study assessments maybe done remotely, such as via phone. 
Subjects who discontinue study treatment prior to Day 28 are encouraged to remain in the study 
to complete all remaining visits and assessments, including for collection of vital status. Subjects 


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who discontinue treatment, for any reason, will need to return for an Early Treatment 
Discontinuation visit 28 days (+7 Days) after the last infusion and may be contacted by phone at 
Day 14 and 28 to check the subject’s survival status. 
See also Section 5 and 6 for additional detail. 
 
5. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
5.1. 
Inclusion Criteria 
In order to be eligible for inclusion in this trial, a Subject must meet all of the following: 
1. Age 40-85 years 
2. Confirmed SARS-CoV-2 infection by a FDA-authorized diagnostic test (e.g., polymerase 
chain reaction [PCR] or other approved assay from any specimen source; note: a positive 
serology/antibody test for SARS-CoV-2 does NOT qualify as evidence of acute COVID- 
19 disease) 
3. Respiratory compromise requiring hospitalization for COVID-19 disease as evidenced by 
at least one (or more) of the following criteria: 
4. Interstitial pneumonia on CXR or HRCT (findings of consolidation or ground glass 
opacities), OR 
5. Peripheral capillary oxygen saturation (SpO2) < 94% on room air, OR 
6. Requiring non-invasive supplemental oxygen (e.g., nasal cannula, face mask) to maintain 
SpO2 
7. Not requiring mechanical ventilation and/or extracorporeal membrane oxygenation 
(ECMO) use at time of randomization 
8. Agrees to not participate in another clinical trial for the treatment of COVID-19 disease 
through Day 28 
9. Subject (or legally authorized representative) able to understand and sign a written 
informed consent form 
 
5.2. 
Exclusion Criteria 
Subjects will be excluded from this trial if any of the following apply: 
1. Female subjects who are pregnant or nursing 
2. Participation in a clinical trial with another investigational drug for COVID-19 disease 
3. Anticipated discharge from the hospital or transfer to another hospital or long-term care 
facility which is not a study site within 72 hours of randomization 
4. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies 


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5.3. 
Early Treatment Termination and Study Withdrawal 
Subjects who do not receive all study drug doses 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. 
Subjects are encouraged to have a final follow-up visit (in person or remotely, such as by phone) 
to check on vital status and general health of the subject. Vital status may also be obtained from 
public records. 
Reasons for terminating treatment early may include: 
• Any safety concern in the Investigator’s opinion, that precludes further study 
participation 
• Female subjects who are pregnant or nursing 
• Participation in a clinical trial with another investigational drug for COVID-19 
disease 
Mandatory reasons for withdrawing the subject from the study include: 
• Withdrawal of Consent 
• Lost To Follow-Up 
5.4. 
Replacement of Study Subjects 
All randomized subjects will be included in the study. Subjects who terminate the study early 
will not be replaced. 
 
5.5. 
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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6. 
STUDY ASSESSMENTS 
6.1. 
Laboratory Assessments, including ABG and SpO2 
Labs will be collected locally for safety and include hematology: CBC (complete blood count) 
and differential, chemistry: CMP (Comprehensive Metabolic Panel), and routine coagulation 
panel (INR, PT, aPTT). 
Arterial blood gas (ABG) will be collected each day the patient is in ICU/CCU, and recorded 
anytime if performed as part of routine care outside ICU/CCU, while hospitalized. 
Peripheral capillary oxygen saturation (SpO2) will be collected each day while hospitalized. 
 
6.2. 
Modified WHO Ordinal Scale 
Assessment of clinical status, using an 8-Point, Modified WHO Ordinal Scale as specified 
below, should be assessed daily, until Day 28: 
1. Not hospitalized, no limitations on activities 
2. Not hospitalized, limitations on activities and/or requiring home oxygen 
3. Hospitalized, not requiring supplemental oxygen, no longer requiring medical care 
4. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care 
(COVID-19-re;ated or otherwise) 
5. Hospitalized, requiring supplemental oxygen 
6. Hospitalized, requiring nasal high-flow oxygen, non-invasive mechanical ventilation, or 
both 
7. Hospitalized, requiring invasive mechanical ventilation, extra-corporeal membrane 
oxygenation (ECMO), or both 
8. Death 
 
6.3. 
Concomitant Medications, Supplemental Oxygen Needs, and other 
Care 
Subjects will be treated according to best available standard-of-care according to the judgment of 
the Investigator. All concomitant medications, including approved and non-approved treatments 
for COVID-19 (e.g., hydroxychloroquine, IL-6 inhibitors, etc.), as well as supplemental oxygen 
needs, will be collected and recorded. 
In addition, the following will be recorded and collected: documentation of SARS-Cov-2 
infection, documentation of any other infection(s) prior to or during hospitalization, and whether 
or not aggressive care is withheld or withdrawn, including the reason for withholding or 
withdrawal of care (e.g., DNR/DNI order, resource limitation). Vital status may also be obtained 
from public records. 


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7. 
STUDY DRUG 
Pamrevlumab is a fully human IgG1 kappa monoclonal antibody that binds to CTGF and is 
formulated as solution for administration by IV infusion. 
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. 
Matching placebo is formulated as solution to be administered in a manner that is identical to 
pamrevlumab infusion. 
 
7.1. 
Study Drug Packaging and Labeling 
Labels will be prepared and will comply with Good Manufacturing Practice requirements for 
labelling and local regulatory guidelines. 
 
7.2. 
Study Drug Storage 
Study drug 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. 
7.3. 
Study Drug Preparation 
Study drug is infused undiluted after pooling the contents of the calculated number of vials in an 
empty infusion bag (total volume of fluid must not exceed 410 mL) according to the Dose 
Preparation Instructions in the IP Manual. 
Study drug solutions for infusion must be stored refrigerated (2°C to 8°C) and administered 
within 24 hours of preparation and administered within 6 hours of stored at room temperature. 
Study drug infusion solutions are administered by IV infusion, using an infusion set with a 0.2 
μm in-line filter. 
 
7.4. 
Study Drug Administration 
Dosing will be based on the weight obtained on Day 1. The total dose is not to exceed 4.1g. The 
dose should be prepared in a volume of fluid that does not exceed 410 mL. Study drug will be 
administered as soon as possible after release from the site’s pharmacy and infused within 24 
hours of preparation. Study drug will be administered by IV infusion, using an infusion set with a 
sterile, nonpyrogenic, low-protein-binding in-line filter (0.2-micron pore size). 
The first infusion shall be completed in approximately 2 hours. If the first infusion is well 
tolerated and no infusion related AEs are observed during the infusion or subsequent 1-hour 
observation period, the second infusion shall be completed in approximately 1 hour. The 2 


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subsequent infusion periods may be shortened to approximately 30 minutes if no infusion-related 
AEs were observed. 
If an infusion-related AE occurs during the subsequent infusion, study drug will be administered 
over approximately 1 hour for the next three infusions. If no drug-related AEs are observed in 
any of these three infusions, the duration of infusion may be decreased 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 reaction, the infusion rate may be slowed or temporarily stopped, depending on the 
severity of symptoms. 
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 
reaction. Signs and symptoms should be managed with appropriate standard of care treatment. 
7.5. 
Study Drug Handling and Disposal 
All study drug must be controlled and tracked. Drug accountability and reconciliation for all 
study drug received should be completed by the study site. All used, unused, and partially used 
study drug should be destroyed on site according to local/institutional policies by the 
pharmacy/authorized staff with approval from Sponsor (or designee), and destruction records 
maintained. IV bags used to infuse study drug can be disposed of per institutional policy. 
 
8. 
ASSESSMENTS OF SAFETY 
8.1. 
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. 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. 
8.2. 
Definitions 
8.2.1. 
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 


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involves an intervention, such as elective cosmetic surgery, or a medical procedure while on 
study, is not considered an adverse event. 
 
8.2.2. 
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 
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. 
 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events 
8.3.1. 
Adverse Event Reporting Period 
The safety reporting period begins after the subject has signed the informed consent and ends 28 
days after the last dose of study drug. 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 8.3.5). Pregnancy reporting requirements are outlined 
in Section 8.3.6. 
Adverse events will be followed until resolved, stable, or until the subject’s last study visit or 
subject is lost to follow-up. 


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8.3.2. 
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. 
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” 
8.3.3. 
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 v5.0) 
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., 


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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. 
8.3.4. 
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. 
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 


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8.3.5. 
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/assent through 28 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 EOS/safety follow-up visit 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). 
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. 
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). 
 
8.3.5.1. 
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 and IRB/EC requirements. 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. 
 
8.3.5.2. 
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 8.3.4. 
If the death occurred within the AE collection and reporting period (signed ICF to 28 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 8.3.5. If the investigator becomes aware of a 


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death occurring after the AE reporting period and considers it related to pamrevlumab, it will be 
reported as an SAE. 
 
8.3.6. 
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. 
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 
28 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 3 months 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. 
 
8.3.7. 
Laboratory or other Test Abnormalities/ Findings 
All new or worsened laboratory abnormalities should 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. 
 
8.3.8. 
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: 


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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) 
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 
 
8.3.9. 
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 and PFTs. 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. 
8.3.9.1. 
Special Reporting Situations 
Special Reporting Situations on FibroGen investigational product Pamrevlumab 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. 
 
8.3.9.2. 
Data Monitoring Committee (DMC) 
An Independent 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 an interim analysis for safety, in 
accordance with the DMC Charter and an Interim Analysis Plan. 


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9. 
STATISTICS 
9.1. 
Sample Size Determination 
The sample size of 65 subjects in each treatment arm will provide about 80% power, at 10% two- 
sided significance level, to detect a 20% difference in the proportion of subjects who never 
received mechanical ventilation / ECMO and alive at Day 28. This assumes that 65% of subjects 
in the placebo arm who never received mechanical ventilation and/or ECMO at Day 28, 
compared to 85% in the pamrevlumab group. 
9.2. 
Analysis Populations 
Enrollment and disposition summaries will be provided on all randomized subjects. 
The Safety Population consists of all subjects who have received at least one dose of study drug. 
All safety summaries will be based on the Safety Population. 
The Intent-To-Treat Set (ITT) consists of all randomized subjects. All efficacy analyses will be 
performed based on the ITT set. 
 
9.3. 
General Considerations 
Baseline value is defined as mean of all screening and Day 1 values prior to the first dose. 
Descriptive summaries will be presented for study parameters including baseline characteristics, 
safety, and efficacy. 
Continuous variables will be reported in mean, standard deviation or standard error, median, Q1- 
Q3, minimum, and maximum. 
Categorical variables will be reported in frequency and percentage of subjects within each 
outcome category. 
 
9.4. 
Statistical Methods 
The analysis of the proportion of subjects who never received mechanical ventilation and/or 
ECMO and are alive at Days 14 and 28, the proportion of subjects alive, discharged home, and 
not on supplemental oxygen at Day 28, proportion of subjects’ clinical status based on an 8-point 
ordinal scale, and proportion of subjects with categorical PaO2/FiO2 ratio endpoints will be 
conducted using logistic regression model with treatment group and adjusting for relevant 
baseline prognostic covariates. 
The number of days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 
28, number of days on mechanical ventilation and/or ECMO at Day 28 will be analyzed using 
the analysis of covariance (ANCOVA). 
Change in PaO2/FiO2 ratio to day 28, change in resting SpO2 adjusted by FiO2 to day 28, change 
in (non-invasive) oxygen supplementation requirements to day 28 will be analyzed using Mixed 
Model for Repeated Measures (MMRM) approach using relevant prognostic factors as 
covariates and treatment and Time and treatment *time interaction 
The analysis will take into account the inter-current events as follows. 


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1. Treatment discontinuation (e.g., due to AEs, Withdrawal by Subject or Physician 
Decision): Missing endpoint will be imputed by the last result prior to discontinuation. 
2. Death: Composite strategy: inter-current event is taken to be a component of the variable. 
For number of days not requiring mechanical ventilation at Day 14, number of days in 
ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28, and number 
of days on mechanical ventilation and/or ECMO at Day 28; days with missing data after 
death will be imputed with the worst result until Day 28. 
3. Treatment discontinuation due to recovering and discharged from hospital: Missing 
endpoint will be imputed with the last result prior to discontinuation. 
Treatment comparison analysis of time to event endpoints, will be performed using cox 
regression model adjusting for relevant baseline prognostic factors. Hazard ratios together with 
95% two-sided confidence intervals for the hazard ratio will be provided. 
Time to recovery by Day 28, time to mechanical ventilation/ECMO or all-cause mortality by 
Day 28, and all-cause mortality at Day 28 (proportion of subjects deceased), and time to death 
from any cause at Day 28 will be analyzed using Cox regression adjusting for relevant 
prognostics factors. Other methods will be used as appropriate. 
 
9.5. 
Safety Analyses 
All subjects who received any dose of pamrevlumab will be included in the safety analyses 
which will summarize treatment-emergent adverse events (TEAEs); treatment-emergent serious 
adverse events (TESAEs); clinical laboratory parameters and vital signs, as well as 
hypersensitivity/anaphylactic reactions. 
 
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) and Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
requirements. 
This protocol, the Informed Consent Form, and the Investigator’s Brochure must be approved by 
a properly constituted IRB/IEC before the study is initiated and before any investigational 
product is shipped to the investigator. 
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. 
Prior to participation in any study-specific procedures, the subject (or legally authorized 
representative) must sign an IRB/IEC-approved written Informed Consent Form (ICF) in his/her 
native language. 


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10.2. 
Communication with the Institutional Review Board or Independent 
Ethics Committee 
This protocol, the Informed Consent Form, the Investigator’s Brochure, 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 re-approval 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 Investigator’s Brochure, 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 (note: all references 
to “subject” in this section refers to the study subject or his/her legally acceptable representative) 
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. 
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 
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. 


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Each subject (or legally authorized representative) must provide his or her consent for the use 
and disclosure of personal health information in accordance with applicable regulatory 
requirements. 
 
10.4. 
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 or other disclosure authorization 
documents signed by the subject, unless permitted or required by applicable law. 
 
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). 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. 
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. 


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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. 
 
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. 
 
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 


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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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13. 
REFERENCES 
Alapati D, Rong M, Chen S, et al. (2011) Connective Tissue Growth Factor Antibody Therapy 
Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats. Am J Respir Cell Mol Biol. 2011 
Dec; 45(6):1169-77 
Bach K, Kuschel C, Hooper S, (2012) High Bias Gas Flows Increase Lung Injury in the 
Ventilated Preterm Lamb. PLoS One. 7(10): e47044 
Bickelhaupt S, Erbel C, Timke C, et al. (2017). Effects of CTGF Blockade on Attenuation and 
Reversal of Radiation-Induced Pulmonary Fibrosis. J Natl Cancer Inst. Aug 1;109(8): djw339 
Bonniaud P, Martin G, Margetts PJ, et al. (2004) Connective tissue growth factor is crucial to 
inducing a profibrotic environment in "fibrosis-resistant" BALB/c mouse lungs. American 
Journal of Respiratory Cell and Molecular Biology 31: (5):510-516 
Booth AJ, Csencsits-Smith K, Wood SC, et al. (2010) Connective Tissue Growth Factor 
Promotes Fibrosis Downstream of TGFB and IL-6 in Chronic Cardiac Allograft Rejection. Am J 
Transplant. 10(2): 220–230 
Cabrera-Benitez NE, Laffey JG, Parotto M, et al. (2014 ) Mechanical ventilation-associated lung 
fibrosis in acute respiratory distress syndrome: a significant contributor to poor outcome. 
Anesthesiology. 121(1):189-98 
Chen N, Zhou M, Dong X, et al. (2020) Epidemiological and clinical characteristics of 99 cases 
of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 
395(10223):507-513 
Clukers J, Lanclus M, Mignot B, Van Holsbeke C, et al. (2018) Quantitative CT analysis using 
functional imaging is superior in describing disease progression in idiopathic pulmonary fibrosis 
compared to forced vital capacity. Respir Res. 19(1):213 
Eyal FG, Ham CR, Parker JC, (2007) Reduction in alveolar macrophages attenuates acute 
ventilator induced lung injury in rats. Intensive Care Med 33:1212–1218 
Frank JA, Wray CM, McAuley DF, (2006) Alveolar macrophages contribute to alveolar barrier 
dysfunction in ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 291: L1191– 
L1198 
Huang C, Wang Y, Li X, et al. (2020) Clinical features of patients infected with 2019 novel 
coronavirus in Wuhan, China. Lancet 395(10223): 497-506 
King TE, Albera C, Bradford WZ, et al. (2009) Effect of interferon gamma-1b on survival in 
patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo- 
controlled trial. Lancet 374: (9685):222-228 
King, TE, Bradford WZ, Castro-Bernardini S, et al. (2014) A Phase 3 Trial of Pirfenidone in 
Patients with Idiopathic Pulmonary Fibrosis, N Engl J Med 370:2083-2092 
Lasky JA, Ortiz LA, Tonthat B, et al. (1998) Connective tissue growth factor mRNA expression 
is upregulated in bleomycin-induced lung fibrosis. The American Journal of Physiology 275: (2 
Pt 1):L365-L371 


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Lipson KE, Wong C, Teng Y, et al. (2012) CTGF is a central mediator of tissue remodeling and 
fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair 5 (Suppl 
1):S24 
Makino K, Makino T, Stawski L, Lipson KE, et al. (2017) Anti-connective tissue growth factor 
(CTGF/CCN2) monoclonal antibody attenuates skin fibrosis in mice models of systemic 
sclerosis. Arthritis Res Ther. 19(1):134 
Mori T, Kawara S, Shinozaki M, et al. (1999) Role and interaction of connective tissue growth 
factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model. 
Journal of Cellular Physiology 181: (1):153-159 
Muro AF, Moretti FA, Moore BB, et al. (2008) An essential role for fibronectin extra type III 
domain A in pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 
177: (6):638-645 
Neesse, A., K.K. Frese, T.E. Bapiro, T. Nakagawa, M.D. Sternlicht, T.W. Seeley, C. Pilarsky, 
D.I. Jodrell, S.M. Spong, and D.A. Tuveson. 2013. 'CTGF antagonism with mAb FG-3019 
enhances chemotherapy response without increasing drug delivery in murine ductal pancreas 
cancer', Proc. Natl. Acad. Sci U. S. A, 110: 12325-30 
Perbal B (2004) CCN proteins: multifunctional signaling regulators. Lancet 363: (9402):62-64 
Perbal B, Tweedie S, Bruford E. (2018) The official unified nomenclature adopted by the HGNC 
calls for the use of the acronyms, CCN1-6, and discontinuation in the use of CYR61, CTGF, 
NOV and WISP 1-3 respectively. J Cell Commun Signal. 12(4):625-629 
Pi L, Fu C, Lu Y, et al. (2018) Vascular Endothelial Cell-Specific Connective Tissue Growth 
Factor (CTGF) Is Necessary for Development of Chronic Hypoxia-Induced Pulmonary 
Hypertension. Front Physiol. 9:138 
Picozzi VJ, Pipas JM, Koong AC, Giaccia AJ, Bahary N, et al. (2017) FG-3019, A Human 
Monoclonal Antibody to Connective Tissue Growth Factor, Combined with Chemotherapy in 
Patients with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma. J Cancer Clin 
Trials 2: 123 
Rachfal AW, Brigstock DR (2005) Structural and Functional Properties of CCN Proteins. Vitam 
Horm 70:69-103 
Raghu G, Brown KK, Bradford WZ, et al. (2004) A placebo-controlled trial of interferon 
gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 350: (2):125-133 
Raghu G, Scholand MB, De Andrade J, et al. (2016). FG-3019 anti-connective tissue growth 
factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary 
fibrosis. Eur Respir J; 47: 1481–1491 
Raghu G, Striker LJ, Hudson LD, et al. (1985) Extracellular matrix in normal and fibrotic human 
lungs. Am Rev Respir Dis. 131(2):281-9 
Richeldi L. (2014) Treatments for idiopathic pulmonary fibrosis. N Engl J Med 371(8):781-784 


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27. (Page 24. 2.6.1) pii: S2213-2600(19)30262-0. doi: 10.1016/S2213-2600(19)30262-0 
 
Richeldi L, Fernández Pérez ER, Costabel U, et al. (2020), Pamrevlumab, an anti-connective 
tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, 
double-blind, placebo-controlled trial. Lancet Respir Med 8(1):25-33 
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Aten, J.W. Hoppener, and R. Goldschmeding. 2006. 'Temporal expression profile and 
distribution pattern indicate a role of connective tissue growth factor (CTGF/CCN-2) in diabetic 
nephropathy in mice', Am J Physiol Renal Physiol, 290: F1344-F54 
Sampson, Hugh A. et al. (2006) Journal of Allergy and Clinical Immunology, Volume 117, Issue 
2, 391– 397 
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RESPIRATORY REVIEWS. 2 (1): 3-9 
Shi-wen X, Stanton LA, Kennedy L, et al. (2006) CCN2 is necessary for adhesive responses to 
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Wallace MJ, Probyn ME, Zahra VA, et al. (2009) Early biomarkers and potential mediators of 
ventilation-induced lung injury in very preterm lambs. Respir Res. 10:19 
Wang D, Hu B, Hu C, et al. (2020) Clinical Characteristics of 138 Hospitalized Patients With 
2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. Feb 7. doi: 
10.1001/jama.2020.1585. [Epub ahead of print] 
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animal models of fibrotic disease. Fibrogenesis Tissue Repair 4: (1):4 
Wu S, Capasso L, Lessa A, et al. (2008) High tidal volume ventilation activates Smad2 and 
upregulates expression of connective tissue growth factor in newborn rat lung. Pediatr Res. 
63(3):245-50 
Xie Y, Wang Y, Liu K, et al. (2019) Correlation analysis between mechanical power, 
transforming growth factor-B1, and connective tissue growth factor levels in acute respiratory 
distress syndrome patients and their clinical significance in pulmonary structural remodeling. 
Medicine. 98 (29):e16531 
Zapol WM, Trelstad RL, Coffey JW, et al. (1979) Pulmonary fibrosis in severe acute respiratory 
failure. Am Rev Respir Dis. 119(4):547-54 
Zhou F., Yu T., Du R., (2020) Clinical course and risk factors for mortality of adult inpatients 
with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–62 
Zisman DA, Schwarz M, Anstrom KJ, et al. (2010) A controlled trial of sildenafil in advanced 
idiopathic pulmonary fibrosis. New England Journal of Medicine 363: (7):620-6 


 
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APPENDIX 1: SCHEDULE OF 
ASSESSMENTS 
Screening 
Treatment 7 
4-Weeks 
after Last 
Dose7 
Up to 2 days prior to Day 1 
Day 1 
Days 2-66 
Day 7 
Days 8-136 
Day 
148 
Days 15-27 6 
Day 
288 
Informed consent 
X 
Eligibility criteria 
X 
Medical History 
X 
Demographic information 
X 
Vital signs 
X 
X1 
X 
X1 
X 
X1 
X 
X1 
Urine pregnancy test2 
X 
Concomitant medication and non-drug therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion 
X 
X 
X 
X 
Local laboratory tests (hematology: CBC and 
differential, chemistry: CMP, coagulation 
parameters: INR, PT, aPTT) 
X 
X 
X 
X 
X 
Arterial Blood Gasses (ABG) 5 
X 
X 
X 
X 
X 
X 
X 
X 
Resting SpO2 4 
X 
X 
X 
X 
X 
X 
X 
X 
Oxygen Supplementation Needs3, 4 
X 
X 
X 
X 
X 
X 
X 
X 
WHO Ordinal Scale 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Survival, ICU and Hospital Discharge Status 
X 
X 
X 
X 
X 
X 
X 
X 
1 On infusion days, vitals taken within 30 minutes prior and 30 min after infusion; otherwise vitals taken daily 2 Women of child-bearing potential. 
3 Need for mechanical ventilation/ECMO, including ventilator settings, or supplemental oxygen, including mode of oxygen delivery. 4 Collected until Day 28 
or hospital discharge, whichever occurs earlier 5 ABGs are collected daily while in ICU/CCU, and recorded if performed as part of routine care outside of ICU/CCU, until 
Day 28 or hospital discharge, whichever occurs earlier 6 if subject is discharged, these visit do not apply; subject should return for infusion visits only. 7 If a subject is 
discharged from hospital before Day 28, and unwilling to return for visits and infusions in an outpatient setting, visits may be conducted remotely for assessment of vital status and safety. If a 
subject is lost to follow-up after hospital discharge, vital status may also be obtained from public records. 8 Visit windows, for outpatient dosing visits ONLY: visit window for Day 
14: +/- 2 days. Visit window for Day 28: +/- 3 days. 
 
 
 
 
 
 
 
Confidential 
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SAP_001.pdf: 
FibroGen, Inc. 
Confidential and Proprietary 
Page 1 of 32 
STATISTICAL ANALYSIS PLAN 
STUDY TITLE: 
Randomized, Double-Blind, Placebo-Controlled Phase 2 
Study of the Efficacy and Safety of Intravenous 
Pamrevlumab, a Monoclonal Antibody Against 
Connective Tissue Growth Factor (CTGF), in 
Hospitalized Patients with Acute COVID-19 Disease 
PROTOCOL NUMBER: 
FGCL-3019-098 
Protocol Version: 
Amendment 1.0 
Version 
1 
Release Date: 
4/20/2021 final 
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 #NCT04432298


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Veeva Document Number: FG-CLPLN-0010 
Version: 1.0 
Status: A 
021
Signature: 
*See appended final page for 21CFR Part 11 compliant approval 
Date: 
 
 
 
 
 
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. 
 
Initiator: 
 
 
 
 
Reviewed by: 
 
Signature: 
*See appended final page for 21CFR Part 11 compliant approval 
Date: 
 
 
Signature: 
*See appended final page for 21CFR Part 11 compliant approval 
Date: 
 
 
 
Signature: 
*See appended final page for 21CFR Part 11 compliant approval 
Date: 
 
 
 
Signature: 
*See appended final page for 21CFR Part 11 compliant approval 
Date: 
 
 
Signature: 
*See appended final page for 21CFR Part 11 compliant approval 
Date: 
 
 


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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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TABLE OF CONTENTS 
1 
Introduction ............................................................................................................................ 8 
2 
Study Objective ...................................................................................................................... 8 
3 
Study Design .......................................................................................................................... 8 
4 
Endpoints ............................................................................................................................... 8 
4.1 Primary Efficacy Endpoint ..................................................................................................... 8 
4.2 Secondary Efficacy Endpoints ............................................................................................... 8 
4.3 Safety Assessments ................................................................................................................ 9 
5 
General Statistical Considerations ......................................................................................... 9 
5.1 Statistical Methodology ......................................................................................................... 9 
5.2 Analysis Populations ............................................................................................................ 10 
5.2.1 
Intent-to-Treat (ITT) Population ..................................................................................... 10 
5.2.2 
Safety Population ............................................................................................................. 10 
5.3 Data Handling Rules and Presentation Specifications ......................................................... 10 
6 
Subject Accountability and Disposition ............................................................................... 11 
7 
Demographics and Baseline Characteristics ........................................................................ 11 
7.1 Demographics and Important Baseline Characteristics ....................................................... 11 
7.2 Medical History ................................................................................................................... 11 
8 
Treatments and Medications ................................................................................................ 11 
8.1 Prior and Concomitant Medications .................................................................................... 11 
8.2 Study Drug Exposure ........................................................................................................... 12 
8.3 Compliance .......................................................................................................................... 12 
9 
Efficacy Analyses ................................................................................................................ 12 
9.1 Primary Efficacy Endpoint - Proportion of Subjects who Never Received Mechanical 
Ventilation and/or ECMO and Alive at Day 28 ................................................................... 12 
9.2 Proportion of Subjects Alive, Discharged, and not on Supplemental Oxygen, Proportion of 
Subjects who Never Received Mechanical Ventilation and/ or ECMO and Alive, and 
Proportion of Subjects Deceased ......................................................................................... 12 
9.3 Time to Recovery, Time to Mechanical Ventilation/ECMO or All-cause Mortality, and 
Time to death ....................................................................................................................... 13 
9.4 Clinical Status Based on the NIAID 8-point Ordinal Scale at Day 28 ................................ 13 
9.5 Number of Days in ICU/CCU and Number of Days on Mechanical Ventilation and/or 
ECMO .................................................................................................................................. 14 


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9.6 Change in Categorical PaO2/FiO2 Ratio (Mild, Moderate, and Severe) .............................. 14 
9.7 Change from Baseline in PaO2/FiO2 Ratio and Change from baseline in Resting 
SpO2/FiO2 at Day 28 ........................................................................................................... 14 
9.8 Change in (Non-invasive) Oxygen Supplementation Requirements at Day 28 ................... 14 
10 
Safety Analyses .................................................................................................................... 14 
10.1 Adverse Events .................................................................................................................... 15 
10.2 Vital Signs ............................................................................................................................ 15 
10.3 Laboratory Tests .................................................................................................................. 15 
11 
Interim Analysis ................................................................................................................... 15 
12 
Reference ............................................................................................................................. 15 
Appendix I 
Handling Missing/Incomplete Dates ..................................................................... 16 
Appendix II 
Standardized meddra queries (SMQ) for Hypersensitivity reaction ..................... 17 
Appendix III   Standardized Meddra queries (SMQ) for Anaphylactic Reaction ........................ 30 


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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ARDS 
Acute Respiratory Distress Syndrome 
AST 
Aspartate Aminotransferase 
ALT 
Alanine Aminotransferase 
ANOVA 
Analysis of Variance 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Class 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
CI 
Confidence Interval 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTGF 
Connective Tissue Growth Factor 
DMC 
Data Monitoring Committee 
DBP 
Diastolic Blood Pressure 
DMP 
Data Management Plan 
ECG 
Electrocardiogram 
EOS 
End of Study 
EOT 
End of Treatment 
HAHA 
Human Anti-Pamrevlumab Antibody 
ICH E9 
International Conference on Harmonization Statistical Principles for 
Clinical Trials 
ITT 
Intent-To-Treat 
IV 
Intravenous 
LLN 
Lower Limit of Normal, value provided by the laboratory 
MAR 
Missing At Random 
MedDRA 
Medical Dictionary for Regulatory Activities 
NIAID 
National Institute of Allergy and Infectious Diseases 


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PCS 
Potentially Clinically Significant 
PT 
Preferred Term 
SMQ 
Standardized MedDRA Queries 
SOC 
System Organ Class 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
TEAE 
Treatment Emergent Adverse Event 
TESAE 
Treatment Emergent Serious Adverse Event 
TLF 
Table, Listing, and Figure 
ULN 
Upper Limit of Normal, value provided by the laboratory 
WHODD 
World Health Organization Drug Dictionary 
WHO 
World Health Organization 


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1 
INTRODUCTION 
The study was terminated by Sponsor on February 19, 2021. Twenty-two subjects were 
randomized for the study at the study termination. This statistical analysis plan (SAP) provides a 
more detailed elaboration of the analyses. 
 
2 
STUDY OBJECTIVE 
To assess the efficacy and safety of intravenous pamrevlumab, an investigational monoclonal 
antibody against connective-tissue growth factor (CTGF), compared to placebo, in hospitalized 
patients with acute COVID-19 disease due to confirmed SARS-COV-2 infection. 
 
3 
STUDY DESIGN 
This is a randomized, double-blind, placebo-controlled phase 2 study of the efficacy and safety of 
intravenous pamrevlumab, a monoclonal antibody against connective-tissue growth factor 
(CTGF), in hospitalized subjects with acute COVID-19 disease due to SARS-CoV-2 infection. 
 
Eligible subjects are those with documented SARS-CoV-2 infection, age 40 to 85 years, with 
evidence of respiratory compromise requiring hospital admission. This age range is chosen to 
enhance detection of potential clinical benefits in subjects at highest risk for developing severe 
COVID-19 disease in this proof-of-concept study. 
 
The total sample size is approximately 130 subjects. Subjects are randomized in a 1:1 ratio, 
according to a pre-determined randomization list from a permuted block design, to receive either 
pamrevlumab or placebo. All subjects are treated with standard-of-care according to the judgment 
of the Investigator. 
 
Study drug is administered as IV infusion on Days 1 (day of randomization), 7, 14 and 28. A 
follow-up visit is performed 4 weeks after the last dose. 
 
 
4 
ENDPOINTS 
4.1 Primary Efficacy Endpoint 
The primary endpoint is the proportion of subjects who never received mechanical ventilation 
and/or ECMO and alive at Day 28. 
4.2 Secondary Efficacy Endpoints 
• Proportion of subjects alive, discharged home, and not on supplemental oxygen at Day 28 
• Proportion of subjects who never received mechanical ventilation and/ or ECMO and 
alive at Day 14 
• Time to recovery by Day 28 based on the NIAID 8-point ordinal scale (Day of recovery 
is defined as the first day on which the patient satisfies one of the following three 


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categories from the ordinal scale: (1) Not hospitalized, no limitations on activities; (2)Not 
hospitalized, limitations on activities and/or requiring home oxygen; (3) Hospitalized, not 
requiring supplemental oxygen, no longer requiring medical care (used if hospitalization 
was extended for infection-control reasons) 
• Clinical status based on the NIAID 8-point ordinal scale (time range: Days 1 to 28) 
• Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at Day 28 
• Days on mechanical ventilation and/or ECMO at Day 28 
• Time to mechanical ventilation/ECMO or all-cause mortality at Day 28 
• All-cause mortality at Day 28 (proportion of subjects deceased) 
• Time to death from any cause at Day 28 
• Change in PaO2/FiO2 ratio as categorical variable using Berlin criteria for ARDS 
categorization (mild, moderate, severe) (time range: Days 1 to 28) 
• Change in PaO2/FiO2 ratio as continuous variable (time range: Days 1 to 28) 
• Change in resting SpO2 adjusted by FiO2 (time range: Days 1 to 28) 
• Change in (non-invasive) oxygen supplementation requirements (time range: Days 1 to 
28) 
4.3 Safety Assessments 
Treatment-emergent adverse events (TEAEs); treatment-emergent serious adverse events 
(TESAEs), including hypersensitivity/ anaphylactic reactions, and vital signs. 
 
5 
GENERAL STATISTICAL CONSIDERATIONS 
All data collected will be included in the data listings. All analyses will be performed using 
SAS® Version 9.3 or higher. 
 
5.1 Statistical Methodology 
There will be no treatment comparison analysis performed for this early terminated study. 
Baseline is defined as the last value on or before the first infusion. 
Continuous variables will be summarized using descriptive statistics: n, mean, standard deviation 
(SD), standard error (SE), median, 25th and 75th percentile, minimum, and maximum. The 2- 
sided 95% confidence interval for the treatment group mean will be presented as appropriate. 
Categorical variables will be tabulated by frequency count and percentage. The confidence 
interval for the proportions for each treatment group will be calculated using the Clopper- 
Pearson method as appropriate. 


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The Clopper-Pearson exact 95% CIs for the dichotomous parameters will be from SAS FREQ 
procedures with option BINOMIAL (EXACT). The 95% CIs for means of normally distributed 
parameters will be from appropriate SAS procedures such as PROC MEANS. 
 
Analyses will be performed using SAS® Version 9.3 or higher. 
 
5.2 Analysis Populations 
The study population is defined through inclusion/exclusion criteria to reflect the targeted patient 
population for study. The details of the inclusion/exclusion criteria can be found in the protocol. 
 
5.2.1 Intent-to-Treat (ITT) Population 
The ITT population is defined as all randomized subjects. Subjects will be analyzed according to 
the treatment as randomized. 
 
5.2.2 Safety Population 
The safety population is defined as all subjects who have received any study medication. 
Subjects will be analyzed according to the treatment as received. 
 
5.3 Data Handling Rules and Presentation Specifications 
The following general guidelines will apply to all statistical analyses and data presentations: 
• Age (Years) = INTCK('YEAR', Birth Date, Date of Informed Consent,'C') where INTCK 
is a SAS function.  Age groups are 18 to 64, 64 to 75, >=75 
• Duration of Ventilation will be calculated as Ventilation Stop Date/Time – 
max(Ventilation Start Date/Time, Randomization Date [we will use 12:00 if no time 
available] or 1st Dose completion Date/Time) 
• All reporting values (mean, SD, 95% CI, etc.) for continuous variables will have the same 
decimal places as the raw data. 
• All percentages will be rounded to one decimal place and lined up by the decimal place. 
The percentage will be suppressed when the count is zero. All analysis statistics will have 
the same decimal place as the raw value. All duration of time will have 1 decimal place. 
• Body weight, height and temperatures will be converted using the following formula: 
- kg = lb/2.2 
- cm = 2.54 x in 
- oC = (5/9) x (oF – 32) 
• Computation formulas: 
BSA = [Weight 0.425 (kg) * Height 0.725 (cm)] x .007184 
BMI = Weight (kg) / (Height (m))2 


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• Mean Arterial Pressure (MAP) will be derived using the following equation: 
MAP = (2/3) * DBP + (1/3) SBP 
• For continuous variables that are recorded as “<X” or “>X”, the value of “X” will be 
used in the calculation of summary statistics. 
• All tables and listings will have a header showing “FibroGen, Inc.”, the protocol number, 
date of the database transfer, and Page x of y. A footer will show the program file 
path/name, output file path/name, run date and run time. 
 
6 
SUBJECT ACCOUNTABILITY AND DISPOSITION 
The number and percentage of subjects who are randomized, dosed, treatment prematurely 
discontinued, and completed the study will be summarized by treatment group. Reasons for 
premature discontinuation as recorded on the Study Disposition page of the CRF will be 
summarized. 
 
7 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
7.1 Demographics and Important Baseline Characteristics 
Demographic parameters and important baseline characteristics will be summarized for ITT 
population by treatment arm. These include but are not be limited to age, age group, sex, 
ethnicity, race, weight, body-mass index (BMI), smoking status, and selective medical history. 
 
Descriptive statistics (n, mean, standard deviation, median, 25-75th percentiles, minimum, and 
maximum) will be presented for continuous variables. Frequency distributions (number and 
percentage of subjects) will be presented for categorical variables. 
Descriptive statistics of baseline efficacy assessments will be presented in their change from 
baseline tables. 
 
 
7.2 Medical History 
Medical history will be listed for the Safety population. 
 
8 
TREATMENTS AND MEDICATIONS 
8.1 Prior and Concomitant Medications 
The use of the prior and concomitant medications will be listed for the ITT population. The 
version of WHODRUG used to code the medication is stated in the data management plan 
(DMP). 
 
Medications are classified into 2 categories: 
 
1. Prior medications - medications that are stopped prior to the first study drug infusion 


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2. Concomitant medications - medications that are used concomitantly with the study drug, 
which includes all medications that started after or not stopped before the first infusion. 
 
 
8.2 Study Drug Exposure 
Duration of study drug exposure in days is calculated as: (last dose date – first dose date + 1). 
Duration of study drug exposure will be summarized as a continuous variable. The duration will 
also be tabulated by the following categories for the Safety population. 
1 to 3 days 
>3 to <=7 days 
>7 to <=14 days 
>14 days <=21 days 
>21 days 
 
Pamrevlumab infusion dose (in mg and mg/Kg), number of infusions during study, and 
interruptions during infusion and reason for interruptions will also be listed. 
 
8.3 Compliance 
The compliance will be presented as % of actual doses of infusion administered over the 
expected total dose of infusions during study for the safety population. That is, compliance = 
actual doses received / scheduled doses * 100%. Treatment compliance will be listed only. 
 
9 
EFFICACY ANALYSES 
Efficacy data will be summarized descriptively based on observed data for the ITT population. 
There will be no imputation performed for the missing endpoint value. 
 
9.1 Primary Efficacy Endpoint - Proportion of Subjects who Never Received Mechanical 
Ventilation and/or ECMO and Alive at Day 28 
Proportion of subjects never received mechanical ventilation and/or ECMO and alive at Day 28 
will be summarized based on observed data. 
 
9.2 Proportion of Subjects Alive, Discharged, and not on Supplemental Oxygen, 
Proportion of Subjects who Never Received Mechanical Ventilation and/ or ECMO 
and Alive, and Proportion of Subjects Deceased 
Proportion of subjects alive, discharged home, and not on supplemental oxygen at Day 28, 
proportion of subjects never received mechanical ventilation and/ or ECMO and alive at Day 14, 
and proportion of all-cause deaths at Day 28 will be summarized descriptively based on observed 
data. 


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9.3 Time to Recovery, Time to Mechanical Ventilation/ECMO or All-cause Mortality, 
and Time to death 
• Time (number of days) from randomization to recovery by Day 28 based on NIAID 8-point 
ordinal scale where recovery is defined as the first day on which the patient satisfies one of 
the following three categories from the ordinal scale: (1) Not hospitalized, no limitations on 
activities; (2) Not hospitalized, limitations on activities and/or requiring home oxygen; (3) 
Hospitalized, not requiring supplemental oxygen, no longer requiring medical care (used if 
hospitalization was extended for infection-control reasons) 
 
Subjects without the event will be censored at the date of last NIAID 8-point ordinal scale 
assessment. 
• Time (number of days) from randomization to mechanical ventilation/ECMO or all-cause 
mortality by Day 28 
For subjects who did not have the event, the last known assessment date of mechanical 
ventilation/ECMO use or survival status, whichever later will be defined as the censoring 
date. 
• Time (number of days) from randomization to death from any cause by Day 28 
For subjects who are alive, the recorded date of last known alive, last contact date, or the date 
of the last clinic visit, whichever latest will be defined as the censoring date. 
 
The number of days of the above endpoints will be summarized descriptively as appropriate. 
 
9.4 Clinical Status Based on the NIAID 8-point Ordinal Scale at Day 28 
Proportion of subjects by response category on the NIAID 8-point ordinal scale will be 
summarized descriptively based on observed data at baseline and Day 28. 
 
 
Order 
Ordinal Level 
1 
Not hospitalized, no limitations on activities 
2 
Not hospitalized, limitations on activities and/or 
requiring home oxygen 
3 
Hospitalized, not requiring supplemental oxygen, no 
longer requiring medical care (used if hospitalization was 
extended for infection-control reasons) 
4 
Hospitalized, not requiring supplemental oxygen, 
requiring ongoing medical care (COVID-19-related or 
otherwise) 
5 
Hospitalized, requiring supplemental oxygen 
6 
Hospitalized, requiring high-flow oxygen, non-invasive 
mechanical ventilation, or both 


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7 
Hospitalized, requiring invasive mechanical ventilation, 
extra-corporeal membrane oxygenation (ECMO), or both 
8 
Death 
Missing 
 
 
 
9.5 Number of Days in ICU/CCU and Number of Days on Mechanical Ventilation and/or 
ECMO 
Total number of days in ICU/CCU (either on or off mechanical ventilation and/or ECMO) at 
Day 28 and total number of days on mechanical ventilation and/or ECMO at Day 28 will be 
summarized descriptively. 
 
9.6 Change in Categorical PaO2/FiO2 Ratio (Mild, Moderate, and Severe) 
PaO2/FiO2 ratio will be defined as a categorical variable using Berlin criteria for ARDS 
categorization (mild, moderate, severe), where mild is PaO2/FiO2 from >200 to <=300, 
moderate is from 100 to <=200, and severe is <100. Proportion of subjects of each category at 
baseline and Day 28 will be summarized descriptively. 
 
 
9.7 Change from Baseline in PaO2/FiO2 Ratio and Change from baseline in Resting 
SpO2/FiO2 at Day 28 
Change from baseline in PaO2/FiO2 ratio at Day 28 and change from baseline in resting SpO2 
adjusted by FiO2 (SpO2/FiO2) at Day 28 will be summarized descriptively. 
 
 
9.8 Change in (Non-invasive) Oxygen Supplementation Requirements at Day 28 
The non-invasive oxygen supplementation requirements include: 
(1) No oxygen supplementation (including breathe room air or have been discharged from 
hospital) 
(2) Non-invasive oxygen supplementation -nasal cannula and face-mask 
 
Change in non-invasive oxygen supplementation requirements will be presented by proportion of 
subjects with non-invasive oxygen supplementation requirements at baseline and at Day 28. 
 
 
10 SAFETY ANALYSES 
The safety analyses will be based on the Safety population. 


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10.1 Adverse Events 
Adverse events will be coded using the latest Medical Dictionary for Regulatory Activities 
(MedDRA), and the final version will be stated in the data management plan (DMP). Per 
protocol, the 28 days after the last dose is the last safety follow up. Therefore, the treatment 
emergent adverse event (TEAE) is defined as an adverse event (AE) with an onset date on or 
after the first infusion up to within 28 days from the last infusion date. An AE with missing start 
date/time will be considered to be a TEAE. 
 
The number (%) of subjects reporting TEAEs in each treatment group will be summarized by 
system organ class and preferred term; by system organ class, preferred term, and severity; and 
by system organ class, preferred term, and relationship to study medication. If more than one 
event occurs with the same SOC/preferred term for the same patient, the patient will be counted 
only once for that SOC/preferred term using the most severe and most related occurrence for the 
summarization by severity and by relationship to the study medication. 
 
In addition, number (%) of subjects with treatment-emergent serious AEs (TESAE), number (%) 
of subjects with non-serious TEAE, number (%) of subjects with most frequent (non-serious) 
TEAE (>=5%), and number (%) of subjects with TEAE leading to discontinuation will be 
summarized by SOC/preferred term. The hypersensitivity and anaphylactic reactions will be 
listed. 
 
Listings of subjects with serious adverse events (SAEs), subjects with adverse events leading to 
discontinuation, and subjects who died will be provided. 
 
10.2 Vital Signs 
The pre- and post-infusion vital signs (systolic and diastolic blood pressure (mmHg), respiration 
rate (breath/min), heart beat (beat/min), Temperature (C) will be listed for the safety population. 
 
10.3 Laboratory Tests 
No laboratory test results were collected. 
 
11 INTERIM ANALYSIS 
The study do not have interim analysis. 
 
12 REFERENCE 
E9 (R1) Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis 
in Clinical Trials 


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APPENDIX I 
HANDLING MISSING/INCOMPLETE DATES 
A. Handling Missing/Incomplete AE Onset Date 
If the AE onset date is incomplete or missing, the following rules will be applied to impute AE 
onset date. 
• If year and month are present, only day is missing, 
a) If AE onset Year/month = Day 1 Year/month, assign onset day = day of Day 1 (Day 1 
is the first infusion day); 
b) If AE onset Year/month ≠ Day 1 Year/month, assign onset day = 1st of the month; 
• If year is present, month and day are missing, or when only month is missing (treating 
day as missing), 
a) If AE onset year = year of Day 1, assign onset date = month and day part of Day 1 
date; 
b) If AE onset year ≠ year of Day 1, assign onset date= January 1st. 
• If onset date is completely missing, assign onset date = date of Day 1. 
If the stop date is complete and the imputed start date as above is after the stop date, the start 
date will be imputed by the stop date. 
 
B. Handling Missing/Incomplete Prior or Concomitant Medication Start/Stop Dates 
For prior or concomitant medications, including rescue medications, incomplete (i.e., partially 
missing) start date is imputed the same way as for the AE described above. When the start date 
and the stop date are both incomplete for a patient, impute the start date first. 
 
Incomplete Stop Date 
The following rules are applied to impute the missing stop date, if needed. 
• If year is present, month and day are missing, or when only month is missing (treating 
day as missing) 
a) If stop year = year of last dose, assign stop date = month and day of the last dose date; 
b) If stop year ≠ year of Day 1, assign stop date= December 31st. 
• If year and month are present, only day is missing, 
a) If AE stop Year/month = Year/month of last dose date, assign stop day = day part of 
last dose date 
b) If AE stop Year/month ≠ Day 1 Year/month, assign onset day = last day of the 
month; 
• Impute CM end date even if ‘ONGOING’ is checked so as to report the CM treatment 
duration in the study if needed. 


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APPENDIX II 
STANDARDIZED MEDDRA QUERIES (SMQ) FOR 
HYPERSENSITIVITY REACTION 
 
 
MedDRA 23.0: Hypersensitivity 
(SMQ) Preferred Term 
Code 
Scope 
Addition 
Version 
Last 
Modified 
Version 
Acquired C1 inhibitor deficiency 
10081035 Narrow 21.0 
21.0 
Acute generalised exanthematous 
pustulosis 
10048799 Narrow 16.0 
16.0 
Administration related reaction 
10069773 Narrow 20.1 
20.1 
Administration site dermatitis 
10075096 Narrow 18.1 
18.1 
Administration site eczema 
10075099 Narrow 18.1 
18.1 
Administration site 
hypersensitivity 
10075102 Narrow 17.1 
17.1 
Administration site rash 
10071156 Narrow 16.0 
16.0 
Administration site recall reaction 
10075964 Narrow 18.1 
18.1 
Administration site urticaria 
10075109 Narrow 17.1 
17.1 
Administration site vasculitis 
10075969 Narrow 18.0 
18.0 
Allergic bronchitis 
10052613 Narrow 16.0 
16.0 
Allergic colitis 
10059447 Narrow 16.0 
16.0 
Allergic cough 
10053779 Narrow 16.0 
16.0 
Allergic cystitis 
10051394 Narrow 16.0 
16.0 
Allergic eosinophilia 
10075185 Narrow 17.1 
17.1 
Allergic gastroenteritis 
10075308 Narrow 17.1 
17.1 
Allergic hepatitis 
10071198 Narrow 16.0 
16.0 
Allergic keratitis 
10057380 Narrow 16.0 
16.0 
Allergic oedema 
10060934 Narrow 16.0 
16.0 
Allergic otitis externa 
10075072 Narrow 17.1 
17.1 
Allergic otitis media 
10061557 Narrow 16.0 
16.0 
Allergic pharyngitis 
10050639 Narrow 16.0 
16.0 
Allergic reaction to excipient 
10078853 Narrow 20.0 
20.0 
Allergic respiratory disease 
10063532 Narrow 16.0 
16.0 
Allergic respiratory symptom 
10063527 Narrow 16.0 
16.0 
Allergic sinusitis 
10049153 Narrow 16.0 
16.0 
Allergic stomatitis 
10079554 Narrow 20.1 
20.1 
Allergic transfusion reaction 
10066173 Narrow 16.0 
16.0 
Allergy alert test positive 
10075479 Narrow 18.0 
18.0 
Allergy test positive 
10056352 Narrow 16.0 
16.0 
Allergy to immunoglobulin 
therapy 
10074079 Narrow 16.1 
16.1 
Allergy to surgical sutures 
10077279 Narrow 19.0 
19.0 


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Allergy to vaccine 
10055048 Narrow 16.0 
16.0 
Anal eczema 
10078682 Narrow 19.1 
22.1 
Anaphylactic reaction 
10002198 Narrow 16.0 
16.0 
Anaphylactic shock 
10002199 Narrow 16.0 
16.0 
Anaphylactic transfusion reaction 
10067113 Narrow 16.0 
16.0 
Anaphylactoid reaction 
10002216 Narrow 16.0 
16.0 
Anaphylactoid shock 
10063119 Narrow 16.0 
16.0 
Anaphylaxis treatment 
10002222 Narrow 16.0 
16.0 
Angioedema 
10002424 Narrow 16.0 
16.0 
Antiallergic therapy 
10064059 Narrow 16.0 
16.0 
Antiendomysial antibody positive 
10065514 Narrow 16.0 
16.0 
Anti-neutrophil cytoplasmic 
antibody positive vasculitis 
10050894 Narrow 16.0 
16.0 
Application site dermatitis 
10003036 Narrow 16.0 
16.0 
Application site eczema 
10050099 Narrow 16.0 
16.0 
Application site hypersensitivity 
10063683 Narrow 16.0 
16.0 
Application site rash 
10003054 Narrow 16.0 
16.0 
Application site recall reaction 
10076024 Narrow 18.1 
18.1 
Application site urticaria 
10050104 Narrow 16.0 
16.0 
Application site vasculitis 
10076027 Narrow 18.0 
18.0 
Arthritis allergic 
10061430 Narrow 16.0 
16.0 
Aspirin-exacerbated respiratory 
disease 
10075084 Narrow 17.1 
17.1 
Atopic cough 
10081492 Narrow 21.1 
21.1 
Atopy 
10003645 Narrow 16.0 
16.0 
Blepharitis allergic 
10005149 Narrow 16.0 
16.0 
Blood immunoglobulin E 
abnormal 
10005589 Narrow 16.0 
16.0 
Blood immunoglobulin E 
increased 
10005591 Narrow 16.0 
16.0 
Bromoderma 
10006404 Narrow 16.0 
16.0 
Bronchospasm 
10006482 Narrow 16.0 
16.0 
Bullous haemorrhagic dermatosis 
10083809 Narrow 23.0 
23.0 
Catheter site dermatitis 
10073992 Narrow 16.1 
16.1 
Catheter site eczema 
10073995 Narrow 16.1 
16.1 
Catheter site hypersensitivity 
10073998 Narrow 16.1 
16.1 
Catheter site rash 
10052271 Narrow 16.0 
16.0 
Catheter site urticaria 
10052272 Narrow 16.0 
16.0 
Catheter site vasculitis 
10074014 Narrow 16.1 
16.1 
Chronic eosinophilic rhinosinusitis 
10071399 Narrow 16.0 
16.0 
Chronic hyperplastic eosinophilic 
sinusitis 
10071380 Narrow 16.0 
16.0 


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Circulatory collapse 
10009192 Narrow 16.0 
16.0 
Circumoral oedema 
10052250 Narrow 16.0 
16.0 
Circumoral swelling 
10081703 Narrow 21.1 
21.1 
Conjunctival oedema 
10010726 Narrow 16.0 
16.0 
Conjunctivitis allergic 
10010744 Narrow 16.0 
16.0 
Contact stomatitis 
10067510 Narrow 16.0 
16.0 
Contrast media allergy 
10066973 Narrow 16.0 
16.0 
Contrast media reaction 
10010836 Narrow 16.0 
16.0 
Corneal oedema 
10011033 Narrow 16.0 
16.0 
Cutaneous vasculitis 
10011686 Narrow 16.0 
16.0 
Dennie-Morgan fold 
10062918 Narrow 16.0 
16.0 
Dermatitis 
10012431 Narrow 16.0 
16.0 
Dermatitis acneiform 
10012432 Narrow 16.0 
16.0 
Dermatitis allergic 
10012434 Narrow 16.0 
16.0 
Dermatitis atopic 
10012438 Narrow 16.0 
16.0 
Dermatitis bullous 
10012441 Narrow 16.0 
16.0 
Dermatitis contact 
10012442 Narrow 16.0 
16.0 
Dermatitis exfoliative 
10012455 Narrow 16.0 
16.0 
Dermatitis exfoliative generalised 
10012456 Narrow 16.0 
16.0 
Dermatitis herpetiformis 
10012468 Narrow 16.0 
16.0 
Dermatitis infected 
10012470 Narrow 16.0 
16.0 
Dermatitis psoriasiform 
10058675 Narrow 16.0 
16.0 
Device allergy 
10072867 Narrow 19.0 
19.0 
Dialysis membrane reaction 
10076665 Narrow 18.1 
18.1 
Distributive shock 
10070559 Narrow 16.0 
16.0 
Documented hypersensitivity to 
administered product 
10076470 Narrow 18.0 
18.0 
Drug eruption 
10013687 Narrow 16.0 
16.0 
Drug hypersensitivity 
10013700 Narrow 16.0 
16.0 
Drug provocation test 
10074350 Narrow 17.0 
17.0 
Drug reaction with eosinophilia 
and systemic symptoms 
10073508 Narrow 16.0 
16.0 
Eczema 
10014184 Narrow 16.0 
16.0 
Eczema infantile 
10014198 Narrow 16.0 
16.0 
Eczema nummular 
10014201 Narrow 16.0 
16.0 
Eczema vaccinatum 
10066042 Narrow 16.0 
16.0 
Eczema vesicular 
10058681 Narrow 16.0 
16.0 
Eczema weeping 
10055182 Narrow 16.0 
16.0 
Encephalitis allergic 
10056387 Narrow 16.0 
16.0 
Encephalopathy allergic 
10014627 Narrow 16.0 
16.0 


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Eosinophilic granulomatosis with 
polyangiitis 
10078117 Narrow 19.1 
19.1 
Epidermal necrosis 
10059284 Narrow 16.0 
16.0 
Epidermolysis 
10053177 Narrow 16.0 
16.0 
Epidermolysis bullosa 
10014989 Narrow 16.0 
16.0 
Epiglottic oedema 
10015029 Narrow 16.0 
16.0 
Erythema multiforme 
10015218 Narrow 16.0 
16.0 
Erythema nodosum 
10015226 Narrow 16.0 
16.0 
Exfoliative rash 
10064579 Narrow 16.0 
16.0 
Eye allergy 
10015907 Narrow 16.0 
16.0 
Eye oedema 
10052139 Narrow 16.0 
16.0 
Eye swelling 
10015967 Narrow 16.0 
16.0 
Eyelid oedema 
10015993 Narrow 16.0 
16.0 
Face oedema 
10016029 Narrow 16.0 
16.0 
Fixed eruption 
10016741 Narrow 16.0 
20.0 
Giant papillary conjunctivitis 
10018258 Narrow 16.0 
16.0 
Gingival oedema 
10049305 Narrow 16.0 
16.0 
Gingival swelling 
10018291 Narrow 16.0 
16.0 
Gleich's syndrome 
10066837 Narrow 16.0 
16.0 
Haemorrhagic urticaria 
10059499 Narrow 16.0 
16.0 
Hand dermatitis 
10058898 Narrow 16.0 
16.0 
Henoch-Schonlein purpura 
10019617 Narrow 16.0 
16.0 
Henoch-Schonlein purpura 
nephritis 
10069440 Narrow 16.0 
16.0 
Heparin-induced 
thrombocytopenia 
10062506 Narrow 16.0 
16.0 
Hereditary angioedema 
10019860 Narrow 16.0 
16.0 
Hereditary angioedema with C1 
esterase inhibitor deficiency 
10080955 Narrow 21.0 
21.0 
Hypersensitivity 
10020751 Narrow 16.0 
16.0 
Hypersensitivity myocarditis 
10081004 Narrow 21.0 
21.0 
Hypersensitivity pneumonitis 
10081988 Narrow 22.0 
22.0 
Hypersensitivity vasculitis 
10020764 Narrow 16.0 
17.0 
Idiopathic urticaria 
10021247 Narrow 16.0 
16.0 
Immediate post-injection reaction 
10067142 Narrow 16.0 
16.0 
Immune thrombocytopenia 
10083842 Narrow 23.0 
23.0 
Immune tolerance induction 
10070581 Narrow 16.0 
16.0 
Implant site dermatitis 
10063855 Narrow 16.0 
16.0 
Implant site hypersensitivity 
10063858 Narrow 16.0 
16.0 
Implant site rash 
10063786 Narrow 16.0 
16.0 
Implant site urticaria 
10063787 Narrow 16.0 
16.0 
Incision site dermatitis 
10073168 Narrow 16.0 
16.0 


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Incision site rash 
10073411 Narrow 16.0 
16.0 
Infusion related hypersensitivity 
reaction 
10082742 Narrow 22.1 
22.1 
Infusion related reaction 
10051792 Narrow 20.1 
20.1 
Infusion site dermatitis 
10065458 Narrow 16.0 
16.0 
Infusion site eczema 
10074850 Narrow 17.0 
17.0 
Infusion site hypersensitivity 
10065471 Narrow 16.0 
16.0 
Infusion site rash 
10059830 Narrow 16.0 
16.0 
Infusion site recall reaction 
10076085 Narrow 18.1 
18.1 
Infusion site urticaria 
10065490 Narrow 16.0 
16.0 
Infusion site vasculitis 
10074851 Narrow 17.0 
17.0 
Injection related reaction 
10071152 Narrow 20.1 
20.1 
Injection site dermatitis 
10022056 Narrow 16.0 
16.0 
Injection site eczema 
10066221 Narrow 18.0 
18.0 
Injection site hypersensitivity 
10022071 Narrow 16.0 
16.0 
Injection site rash 
10022094 Narrow 16.0 
16.0 
Injection site recall reaction 
10066797 Narrow 18.1 
18.1 
Injection site urticaria 
10022107 Narrow 16.0 
16.0 
Injection site vasculitis 
10067995 Narrow 16.0 
16.0 
Instillation site hypersensitivity 
10073612 Narrow 18.0 
18.0 
Instillation site rash 
10073622 Narrow 18.0 
18.0 
Instillation site urticaria 
10073627 Narrow 18.0 
18.0 
Interstitial granulomatous 
dermatitis 
10067972 Narrow 16.0 
16.0 
Intestinal angioedema 
10076229 Narrow 18.0 
18.0 
Iodine allergy 
10052098 Narrow 16.0 
16.0 
Kaposi's varicelliform eruption 
10051891 Narrow 16.0 
16.0 
Kounis syndrome 
10069167 Narrow 16.0 
16.0 
Laryngeal oedema 
10023845 Narrow 16.0 
16.0 
Laryngitis allergic 
10064866 Narrow 16.0 
16.0 
Laryngospasm 
10023891 Narrow 16.0 
16.0 
Laryngotracheal oedema 
10023893 Narrow 16.0 
16.0 
Limbal swelling 
10070492 Narrow 16.0 
16.0 
Lip oedema 
10024558 Narrow 16.0 
16.0 
Lip swelling 
10024570 Narrow 16.0 
16.0 
Mast cell degranulation present 
10076606 Narrow 18.1 
18.1 
Medical device site dermatitis 
10075572 Narrow 18.0 
18.0 
Medical device site eczema 
10075575 Narrow 18.0 
18.0 
Medical device site 
hypersensitivity 
10075579 Narrow 18.0 
18.0 
Medical device site rash 
10075585 Narrow 18.0 
18.0 
Medical device site recall reaction 
10076140 Narrow 18.1 
18.1 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 22 of 32 
 
 
 
 
Medical device site urticaria 
10075588 Narrow 18.0 
18.0 
Mouth swelling 
10075203 Narrow 17.1 
17.1 
Mucocutaneous rash 
10056671 Narrow 16.0 
16.0 
Multiple allergies 
10028164 Narrow 16.0 
16.0 
Nephritis allergic 
10029120 Narrow 16.0 
16.0 
Nikolsky's sign 
10029415 Narrow 16.0 
16.0 
Nodular rash 
10075807 Narrow 18.0 
18.1 
Nutritional supplement allergy 
10084049 Narrow 23.0 
23.0 
Oculomucocutaneous syndrome 
10030081 Narrow 16.0 
16.0 
Oculorespiratory syndrome 
10067317 Narrow 16.0 
16.0 
Oedema mouth 
10030110 Narrow 16.0 
16.0 
Oral allergy syndrome 
10068355 Narrow 16.0 
16.0 
Oropharyngeal blistering 
10067950 Narrow 16.0 
16.0 
Oropharyngeal oedema 
10078783 Narrow 20.0 
20.0 
Oropharyngeal spasm 
10031111 Narrow 16.0 
16.0 
Oropharyngeal swelling 
10031118 Narrow 16.0 
16.0 
Palatal oedema 
10056998 Narrow 16.0 
16.0 
Palatal swelling 
10074403 Narrow 17.0 
17.0 
Palisaded neutrophilic 
granulomatous dermatitis 
10068809 Narrow 16.0 
17.1 
Palpable purpura 
10056872 Narrow 16.0 
16.0 
Pathergy reaction 
10074332 Narrow 17.0 
17.0 
Perioral dermatitis 
10034541 Narrow 16.0 
21.0 
Periorbital oedema 
10034545 Narrow 16.0 
16.0 
Periorbital swelling 
10056647 Narrow 16.0 
21.1 
Pharyngeal oedema 
10034829 Narrow 16.0 
16.0 
Pharyngeal swelling 
10082270 Narrow 22.0 
22.0 
Procedural shock 
10080894 Narrow 21.0 
21.0 
Pruritus allergic 
10063438 Narrow 16.0 
16.0 
Radioallergosorbent test positive 
10037789 Narrow 16.0 
16.0 
Rash 
10037844 Narrow 16.0 
16.0 
Rash erythematous 
10037855 Narrow 16.0 
16.0 
Rash follicular 
10037857 Narrow 16.0 
16.0 
Rash macular 
10037867 Narrow 16.0 
16.0 
Rash maculo-papular 
10037868 Narrow 16.0 
16.0 
Rash maculovesicular 
10050004 Narrow 16.0 
16.0 
Rash morbilliform 
10037870 Narrow 16.0 
16.0 
Rash neonatal 
10037871 Narrow 16.0 
16.0 
Rash papulosquamous 
10037879 Narrow 16.0 
16.0 
Rash pruritic 
10037884 Narrow 16.0 
16.0 
Rash pustular 
10037888 Narrow 16.0 
16.0 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
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Page 23 of 32 
 
 
 
 
Rash rubelliform 
10057984 Narrow 16.0 
16.0 
Rash scarlatiniform 
10037890 Narrow 16.0 
16.0 
Rash vesicular 
10037898 Narrow 16.0 
16.0 
Reaction to azo-dyes 
10037973 Narrow 16.0 
16.0 
Reaction to colouring 
10037974 Narrow 16.0 
16.0 
Reaction to excipient 
10079925 Narrow 20.1 
20.1 
Reaction to food additive 
10037977 Narrow 22.0 
22.0 
Reaction to preservatives 
10064788 Narrow 16.0 
16.0 
Red man syndrome 
10038192 Narrow 16.0 
16.0 
Rhinitis allergic 
10039085 Narrow 16.0 
16.0 
Scleral oedema 
10057431 Narrow 16.0 
16.0 
Scleritis allergic 
10051126 Narrow 16.0 
16.0 
Scrotal dermatitis 
10083260 Narrow 23.0 
23.0 
Scrotal oedema 
10039755 Narrow 16.0 
16.0 
Serum sickness 
10040400 Narrow 16.0 
16.0 
Serum sickness-like reaction 
10040402 Narrow 16.0 
16.0 
Shock 
10040560 Narrow 16.0 
16.0 
Shock symptom 
10040581 Narrow 16.0 
18.1 
SJS-TEN overlap 
10083164 Narrow 22.1 
22.1 
Skin necrosis 
10040893 Narrow 16.0 
16.0 
Skin reaction 
10040914 Narrow 16.0 
16.0 
Skin test positive 
10040934 Narrow 16.0 
16.0 
Solar urticaria 
10041307 Narrow 16.0 
16.0 
Solvent sensitivity 
10041316 Narrow 16.0 
16.0 
Stevens-Johnson syndrome 
10042033 Narrow 16.0 
16.0 
Stoma site hypersensitivity 
10074509 Narrow 17.0 
17.0 
Stoma site rash 
10059071 Narrow 17.0 
17.0 
Swelling face 
10042682 Narrow 16.0 
16.0 
Swelling of eyelid 
10042690 Narrow 16.0 
21.1 
Swollen tongue 
10042727 Narrow 16.0 
16.0 
Symmetrical drug-related 
intertriginous and flexural 
exanthema 
10078325 Narrow 19.1 
19.1 
Therapeutic product cross- 
reactivity 
10079645 Narrow 20.1 
20.1 
Tongue oedema 
10043967 Narrow 16.0 
16.0 
Toxic epidermal necrolysis 
10044223 Narrow 16.0 
16.0 
Toxic skin eruption 
10057970 Narrow 16.0 
16.0 
Tracheal oedema 
10044296 Narrow 16.0 
16.0 
Type I hypersensitivity 
10045240 Narrow 16.0 
16.0 
Type II hypersensitivity 
10054000 Narrow 16.0 
16.0 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
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Page 24 of 32 
 
 
 
 
Type III immune complex 
mediated reaction 
10053614 Narrow 16.0 
16.0 
Type IV hypersensitivity reaction 
10053613 Narrow 16.0 
16.0 
Urticaria 
10046735 Narrow 16.0 
16.0 
Urticaria cholinergic 
10046740 Narrow 16.0 
16.0 
Urticaria chronic 
10052568 Narrow 16.0 
16.0 
Urticaria contact 
10046742 Narrow 16.0 
16.0 
Urticaria papular 
10046750 Narrow 16.0 
16.0 
Urticaria physical 
10046751 Narrow 16.0 
16.0 
Urticaria pigmentosa 
10046752 Narrow 16.0 
16.0 
Urticaria vesiculosa 
10046755 Narrow 16.0 
16.0 
Urticarial dermatitis 
10082290 Narrow 22.0 
22.0 
Urticarial vasculitis 
10048820 Narrow 16.0 
19.0 
Vaccination site dermatitis 
10069477 Narrow 16.0 
16.0 
Vaccination site eczema 
10076161 Narrow 18.1 
18.1 
Vaccination site exfoliation 
10069489 Narrow 16.0 
16.0 
Vaccination site hypersensitivity 
10068880 Narrow 16.0 
16.0 
Vaccination site rash 
10069482 Narrow 16.0 
16.0 
Vaccination site recall reaction 
10076188 Narrow 18.1 
18.1 
Vaccination site urticaria 
10069622 Narrow 16.0 
16.0 
Vaccination site vasculitis 
10076191 Narrow 18.1 
18.1 
Vaccination site vesicles 
10069623 Narrow 16.0 
16.0 
Vaginal ulceration 
10046943 Narrow 16.0 
16.0 
Vasculitic rash 
10047111 Narrow 16.0 
16.0 
Vernal keratoconjunctivitis 
10081000 Narrow 21.0 
21.0 
Vessel puncture site rash 
10077117 Narrow 18.1 
18.1 
Vessel puncture site vesicles 
10077813 Narrow 19.0 
19.0 
Vulval eczema 
10066273 Narrow 16.0 
22.1 
Vulval ulceration 
10047768 Narrow 16.0 
16.0 
Vulvovaginal rash 
10071588 Narrow 16.0 
16.0 
Vulvovaginal ulceration 
10050181 Narrow 16.0 
16.0 
Vulvovaginitis allergic 
10080783 Narrow 21.0 
21.0 
Acute respiratory failure 
10001053 Broad 
16.0 
16.0 
Administration site 
photosensitivity reaction 
10075961 Broad 
18.0 
18.0 
Airway remodelling 
10075289 Broad 
17.1 
17.1 
Allergy to chemicals 
10061626 Broad 
16.0 
16.0 
Allergy to fermented products 
10054929 Broad 
16.0 
16.0 
Alpha tumour necrosis factor 
increased 
10059982 Broad 
16.0 
16.0 
Alveolitis 
10001889 Broad 
16.0 
16.0 
Antibody test abnormal 
10061425 Broad 
16.0 
16.0 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 25 of 32 
 
 
 
 
Antibody test positive 
10061427 Broad 
16.0 
16.0 
Anti-insulin antibody increased 
10053815 Broad 
16.0 
16.0 
Anti-insulin antibody positive 
10053814 Broad 
16.0 
16.0 
Anti-insulin receptor antibody 
increased 
10068226 Broad 
16.0 
16.0 
Anti-insulin receptor antibody 
positive 
10068225 Broad 
16.0 
16.0 
Application site photosensitivity 
reaction 
10058730 Broad 
18.0 
18.0 
Asthma 
10003553 Broad 
16.0 
16.0 
Asthma late onset 
10003559 Broad 
16.0 
16.0 
Asthma-chronic obstructive 
pulmonary disease overlap 
syndrome 
10077005 Broad 
18.1 
18.1 
Asthmatic crisis 
10064823 Broad 
16.0 
16.0 
Auricular swelling 
10003800 Broad 
16.0 
16.0 
Blister 
10005191 Broad 
16.0 
16.0 
Blister rupture 
10073385 Broad 
16.0 
16.1 
Blood immunoglobulin A 
abnormal 
10005584 Broad 
16.0 
16.0 
Blood immunoglobulin A 
increased 
10005586 Broad 
16.0 
16.0 
Blood immunoglobulin D 
increased 
10063244 Broad 
16.0 
16.0 
Blood immunoglobulin G 
abnormal 
10005594 Broad 
16.0 
16.0 
Blood immunoglobulin G 
increased 
10005596 Broad 
16.0 
16.0 
Blood immunoglobulin M 
abnormal 
10005599 Broad 
16.0 
16.0 
Blood immunoglobulin M 
increased 
10005601 Broad 
16.0 
16.0 
Bronchial hyperreactivity 
10066091 Broad 
16.0 
16.0 
Bronchial oedema 
10056695 Broad 
16.0 
16.0 
Bullous impetigo 
10006563 Broad 
16.0 
16.0 
Caffeine allergy 
10074895 Broad 
17.1 
17.1 
Capillaritis 
10068406 Broad 
16.0 
16.0 
Charcot-Leyden crystals 
10008413 Broad 
16.0 
16.0 
Cheilitis 
10008417 Broad 
22.0 
22.0 
Childhood asthma 
10081274 Broad 
21.1 
21.1 
Choking 
10008589 Broad 
16.0 
16.0 
Choking sensation 
10008590 Broad 
16.0 
16.0 
Complement factor C1 decreased 
10051552 Broad 
16.0 
20.1 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 26 of 32 
 
 
 
 
Complement factor C2 decreased 
10051555 Broad 
16.0 
20.1 
Complement factor C3 decreased 
10050981 Broad 
16.0 
20.1 
Complement factor C4 decreased 
10050983 Broad 
16.0 
20.1 
Complement factor decreased 
10061048 Broad 
16.0 
20.1 
Conjunctivitis 
10010741 Broad 
16.0 
16.0 
Corneal exfoliation 
10064489 Broad 
16.0 
16.0 
Cough variant asthma 
10063076 Broad 
16.0 
23.0 
Cytokine release syndrome 
10052015 Broad 
17.0 
17.0 
Cytokine storm 
10050685 Broad 
17.0 
17.0 
Ear swelling 
10014025 Broad 
16.0 
16.1 
Eosinophil count abnormal 
10061125 Broad 
16.0 
16.0 
Eosinophil count increased 
10014945 Broad 
16.0 
16.0 
Eosinophil percentage abnormal 
10058133 Broad 
16.0 
16.0 
Eosinophil percentage increased 
10052222 Broad 
16.0 
16.0 
Eosinophilia 
10014950 Broad 
16.0 
16.0 
Eosinophilia myalgia syndrome 
10014952 Broad 
16.0 
16.0 
Eosinophilic bronchitis 
10065563 Broad 
16.0 
16.0 
Eosinophilic oesophagitis 
10064212 Broad 
16.0 
16.0 
Eosinophilic pneumonia 
10014962 Broad 
16.0 
16.0 
Eosinophilic pneumonia acute 
10052832 Broad 
16.0 
16.0 
Eosinophilic pneumonia chronic 
10052833 Broad 
16.0 
16.0 
Erythema 
10015150 Broad 
16.0 
16.0 
Flushing 
10016825 Broad 
16.0 
16.0 
Gastrointestinal oedema 
10058061 Broad 
16.0 
16.0 
Generalised oedema 
10018092 Broad 
16.0 
16.0 
Genital rash 
10018175 Broad 
16.0 
16.0 
Genital swelling 
10067639 Broad 
16.0 
16.0 
Haemolytic transfusion reaction 
10067122 Broad 
16.0 
16.0 
HLA marker study positive 
10067937 Broad 
16.0 
16.0 
Human anti-hamster antibody 
increased 
10082107 Broad 
22.0 
22.0 
Human anti-hamster antibody 
positive 
10082109 Broad 
22.0 
22.0 
Immune complex level increased 
10064650 Broad 
16.0 
16.0 
Immunoglobulins abnormal 
10021497 Broad 
16.0 
16.0 
Immunoglobulins increased 
10021500 Broad 
16.0 
16.0 
Immunology test abnormal 
10061214 Broad 
16.0 
16.0 
Implant site photosensitivity 
10073415 Broad 
18.0 
18.0 
Infusion site photosensitivity 
reaction 
10065486 Broad 
18.0 
18.0 
Injection site panniculitis 
10083040 Broad 
22.1 
22.1 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 27 of 32 
 
 
 
 
Injection site photosensitivity 
reaction 
10053396 Broad 
18.0 
18.0 
Interstitial lung disease 
10022611 Broad 
16.0 
16.0 
Laryngeal dyspnoea 
10052390 Broad 
16.0 
16.0 
Laryngeal obstruction 
10059639 Broad 
16.0 
16.0 
Leukotriene increased 
10064663 Broad 
16.0 
16.0 
Lip exfoliation 
10064482 Broad 
16.0 
16.0 
Localised oedema 
10048961 Broad 
16.0 
16.0 
Macrophage inflammatory protein- 
1 alpha increased 
10083049 Broad 
22.1 
22.1 
Mechanical urticaria 
10068773 Broad 
16.0 
16.0 
Medical device site 
photosensitivity reaction 
10076137 Broad 
18.0 
18.0 
Mesenteric panniculitis 
10063031 Broad 
16.0 
16.0 
Monocyte chemotactic protein-2 
increased 
10083043 Broad 
22.1 
22.1 
Mouth ulceration 
10028034 Broad 
16.0 
16.0 
Mucocutaneous ulceration 
10028084 Broad 
16.0 
16.0 
Mucosa vesicle 
10028103 Broad 
16.0 
16.0 
Mucosal erosion 
10061297 Broad 
16.0 
16.0 
Mucosal exfoliation 
10064486 Broad 
16.0 
16.0 
Mucosal necrosis 
10067993 Broad 
16.0 
16.0 
Mucosal ulceration 
10028124 Broad 
16.0 
16.0 
Nasal crease 
10078581 Broad 
19.1 
19.1 
Necrotising panniculitis 
10062579 Broad 
16.0 
16.0 
Neurodermatitis 
10029263 Broad 
16.0 
16.0 
Neutralising antibodies positive 
10064980 Broad 
16.0 
16.0 
Noninfective conjunctivitis 
10074701 Broad 
17.0 
17.0 
Non-neutralising antibodies 
positive 
10064982 Broad 
16.0 
16.0 
Occupational asthma 
10070836 Broad 
16.0 
16.0 
Occupational dermatitis 
10030012 Broad 
16.0 
16.1 
Oedema mucosal 
10030111 Broad 
16.0 
16.0 
Oral mucosal exfoliation 
10064487 Broad 
16.0 
16.0 
Orbital oedema 
10031051 Broad 
16.0 
16.0 
Panniculitis 
10033675 Broad 
16.0 
16.0 
Penile exfoliation 
10064485 Broad 
16.0 
16.0 
Penile oedema 
10066774 Broad 
16.0 
16.0 
Penile rash 
10082571 Broad 
22.1 
22.1 
Penile swelling 
10034319 Broad 
16.0 
16.0 
Perineal rash 
10075364 Broad 
17.1 
17.1 
Perivascular dermatitis 
10064986 Broad 
16.0 
16.0 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 28 of 32 
 
 
 
 
Photosensitivity reaction 
10034972 Broad 
16.0 
16.0 
Pneumonitis 
10035742 Broad 
16.0 
16.0 
Prurigo 
10037083 Broad 
16.0 
16.0 
Pruritus 
10037087 Broad 
16.0 
16.0 
Pulmonary eosinophilia 
10037382 Broad 
16.0 
16.0 
Reactive airways dysfunction 
syndrome 
10070832 Broad 
16.0 
16.0 
Respiratory arrest 
10038669 Broad 
16.0 
16.0 
Respiratory distress 
10038687 Broad 
16.0 
16.0 
Respiratory failure 
10038695 Broad 
16.0 
16.0 
Respiratory tract oedema 
10070774 Broad 
16.0 
16.0 
Reversible airways obstruction 
10062109 Broad 
16.0 
16.0 
Rhinitis perennial 
10039094 Broad 
16.0 
16.0 
Scrotal exfoliation 
10081178 Broad 
21.1 
21.1 
Scrotal swelling 
10039759 Broad 
16.0 
16.0 
Seasonal allergy 
10048908 Broad 
16.0 
16.0 
Septal panniculitis 
10056876 Broad 
16.0 
16.0 
Skin erosion 
10040840 Broad 
16.0 
16.0 
Skin exfoliation 
10040844 Broad 
16.0 
16.0 
Skin oedema 
10058679 Broad 
16.0 
16.0 
Skin swelling 
10053262 Broad 
16.0 
16.0 
Sneezing 
10041232 Broad 
16.0 
16.0 
Status asthmaticus 
10041961 Broad 
16.0 
16.0 
Stomatitis 
10042128 Broad 
16.0 
16.0 
Streptokinase antibody increased 
10053797 Broad 
16.0 
16.0 
Stridor 
10042241 Broad 
16.0 
16.0 
Suffocation feeling 
10042444 Broad 
16.0 
16.0 
Sunscreen sensitivity 
10083629 Broad 
23.0 
23.0 
Throat tightness 
10043528 Broad 
16.0 
16.0 
Tongue exfoliation 
10064488 Broad 
16.0 
16.0 
Tracheal obstruction 
10044291 Broad 
16.0 
16.0 
Tracheostomy 
10044320 Broad 
16.0 
16.0 
Transplantation associated food 
allergy 
10075008 Broad 
17.1 
17.1 
Upper airway obstruction 
10067775 Broad 
16.0 
16.0 
Vaccination site photosensitivity 
reaction 
10076186 Broad 
18.0 
18.0 
Vaginal oedema 
10063818 Broad 
16.0 
16.0 
Visceral oedema 
10065768 Broad 
16.0 
16.0 
Vulval oedema 
10047763 Broad 
16.0 
16.0 
Vulvovaginal exfoliation 
10083435 Broad 
23.0 
23.0 
Vulvovaginal swelling 
10071211 Broad 
16.0 
16.0 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 29 of 32 
 
 
 
 
Wheezing 
10047924 Broad 
16.0 
16.0 


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Statistical Analysis Plan, Version 1.0 
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04/20/   021 
FibroGen, Inc. 
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Page 30 of 32 
 
 
 
APPENDIX III STANDARDIZED MEDDRA QUERIES (SMQ) FOR ANAPHYLACTIC 
REACTION 
 
 
MedDRA 23.0: Anaphylactic 
reaction (SMQ) Preferred Term 
Code 
Scope 
Category 
Addition 
Version 
Last 
Modified 
Version 
Anaphylactic reaction 
10002198 
Narrow 
A 
8.1 
8.1 
Anaphylactic shock 
10002199 
Narrow 
A 
8.1 
8.1 
Anaphylactic transfusion reaction 
10067113 
Narrow 
A 
11.1 
11.1 
Anaphylactoid reaction 
10002216 
Narrow 
A 
8.1 
8.1 
Anaphylactoid shock 
10063119 
Narrow 
A 
8.1 
8.1 
Circulatory collapse 
10009192 
Narrow 
A 
8.1 
8.1 
Dialysis membrane reaction 
10076665 
Narrow 
A 
18.1 
18.1 
Kounis syndrome 
10069167 
Narrow 
A 
12.0 
12.0 
Procedural shock 
10080894 
Narrow 
A 
21.0 
21.0 
Shock 
10040560 
Narrow 
A 
8.1 
8.1 
Shock symptom 
10040581 
Narrow 
A 
8.1 
18.1 
Type I hypersensitivity 
10045240 
Narrow 
A 
8.1 
8.1 
Acute respiratory failure 
10001053 
Broad 
B 
8.1 
8.1 
Asthma 
10003553 
Broad 
B 
8.1 
8.1 
Bronchial oedema 
10056695 
Broad 
B 
8.1 
8.1 
Bronchospasm 
10006482 
Broad 
B 
8.1 
8.1 
Cardio-respiratory distress 
10049874 
Broad 
B 
8.1 
8.1 
Chest discomfort 
10008469 
Broad 
B 
8.1 
8.1 
Choking 
10008589 
Broad 
B 
8.1 
8.1 
Choking sensation 
10008590 
Broad 
B 
8.1 
8.1 
Circumoral oedema 
10052250 
Broad 
B 
11.0 
11.0 
Cough 
10011224 
Broad 
B 
8.1 
8.1 
Cough variant asthma 
10063076 
Broad 
B 
8.1 
23.0 
Cyanosis 
10011703 
Broad 
B 
14.1 
15.0 
Dyspnoea 
10013968 
Broad 
B 
8.1 
8.1 
Hyperventilation 
10020910 
Broad 
B 
8.1 
8.1 
Irregular breathing 
10076213 
Broad 
B 
18.0 
18.1 
Laryngeal dyspnoea 
10052390 
Broad 
B 
8.1 
8.1 
Laryngeal oedema 
10023845 
Broad 
B 
8.1 
8.1 
Laryngospasm 
10023891 
Broad 
B 
8.1 
8.1 
Laryngotracheal oedema 
10023893 
Broad 
B 
8.1 
8.1 
Mouth swelling 
10075203 
Broad 
B 
17.1 
17.1 
Nasal obstruction 
10028748 
Broad 
B 
12.1 
14.0 
Oedema mouth 
10030110 
Broad 
B 
8.1 
8.1 
Oropharyngeal oedema 
10078783 
Broad 
B 
20.0 
20.0 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 31 of 32 
 
 
 
 
Oropharyngeal spasm 
10031111 
Broad 
B 
8.1 
8.1 
Oropharyngeal swelling 
10031118 
Broad 
B 
8.1 
8.1 
Pharyngeal oedema 
10034829 
Broad 
B 
20.0 
20.0 
Pharyngeal swelling 
10082270 
Broad 
B 
22.0 
22.0 
Respiratory arrest 
10038669 
Broad 
B 
8.1 
8.1 
Respiratory distress 
10038687 
Broad 
B 
8.1 
8.1 
Respiratory failure 
10038695 
Broad 
B 
8.1 
8.1 
Reversible airways obstruction 
10062109 
Broad 
B 
8.1 
8.1 
Sensation of foreign body 
10061549 
Broad 
B 
8.1 
8.1 
Sneezing 
10041232 
Broad 
B 
8.1 
8.1 
Stridor 
10042241 
Broad 
B 
8.1 
8.1 
Swollen tongue 
10042727 
Broad 
B 
8.1 
8.1 
Tachypnoea 
10043089 
Broad 
B 
14.1 
14.1 
Throat tightness 
10043528 
Broad 
B 
8.1 
8.1 
Tongue oedema 
10043967 
Broad 
B 
8.1 
8.1 
Tracheal obstruction 
10044291 
Broad 
B 
8.1 
8.1 
Tracheal oedema 
10044296 
Broad 
B 
8.1 
8.1 
Upper airway obstruction 
10067775 
Broad 
B 
11.0 
11.0 
Wheezing 
10047924 
Broad 
B 
8.1 
8.1 
Acquired C1 inhibitor deficiency 
10081035 
Broad 
C 
21.0 
21.0 
Allergic oedema 
10060934 
Broad 
C 
8.1 
8.1 
Angioedema 
10002424 
Broad 
C 
8.1 
10.0 
Circumoral swelling 
10081703 
Broad 
C 
21.1 
21.1 
Erythema 
10015150 
Broad 
C 
8.1 
8.1 
Eye oedema 
10052139 
Broad 
C 
8.1 
8.1 
Eye pruritus 
10052140 
Broad 
C 
14.1 
14.1 
Eye swelling 
10015967 
Broad 
C 
8.1 
8.1 
Eyelid oedema 
10015993 
Broad 
C 
8.1 
8.1 
Face oedema 
10016029 
Broad 
C 
8.1 
8.1 
Flushing 
10016825 
Broad 
C 
8.1 
8.1 
Hereditary angioedema with C1 
esterase inhibitor deficiency 
10080955 
Broad 
C 
21.0 
21.0 
Injection site urticaria 
10022107 
Broad 
C 
14.1 
14.1 
Lip oedema 
10024558 
Broad 
C 
8.1 
9.1 
Lip swelling 
10024570 
Broad 
C 
8.1 
9.1 
Nodular rash 
10075807 
Broad 
C 
18.0 
18.1 
Ocular hyperaemia 
10030041 
Broad 
C 
14.1 
14.1 
Oedema 
10030095 
Broad 
C 
8.1 
8.1 
Oedema blister 
10080039 
Broad 
C 
20.1 
20.1 
Periorbital oedema 
10034545 
Broad 
C 
8.1 
8.1 
Periorbital swelling 
10056647 
Broad 
C 
8.1 
21.1 


FG-CLPLN-0010 
Statistical Analysis Plan, Version 1.0 
FGCL-3019-098 
04/20/   021 
FibroGen, Inc. 
Confidential and Proprietary 
Page 32 of 32 
 
 
 
 
Pruritus 
10037087 
Broad 
C 
8.1 
8.1 
Pruritus allergic 
10063438 
Broad 
C 
8.1 
8.1 
Rash 
10037844 
Broad 
C 
8.1 
8.1 
Rash erythematous 
10037855 
Broad 
C 
8.1 
8.1 
Rash pruritic 
10037884 
Broad 
C 
8.1 
8.1 
Skin swelling 
10053262 
Broad 
C 
8.1 
8.1 
Swelling 
10042674 
Broad 
C 
8.1 
8.1 
Swelling face 
10042682 
Broad 
C 
8.1 
8.1 
Swelling of eyelid 
10042690 
Broad 
C 
8.1 
21.1 
Urticaria 
10046735 
Broad 
C 
8.1 
8.1 
Urticaria papular 
10046750 
Broad 
C 
8.1 
8.1 
Blood pressure decreased 
10005734 
Broad 
D 
8.1 
8.1 
Blood pressure diastolic decreased 
10005737 
Broad 
D 
8.1 
8.1 
Blood pressure systolic decreased 
10005758 
Broad 
D 
8.1 
8.1 
Cardiac arrest 
10007515 
Broad 
D 
8.1 
8.1 
Cardio-respiratory arrest 
10007617 
Broad 
D 
8.1 
8.1 
Cardiovascular insufficiency 
10065929 
Broad 
D 
9.0 
9.0 
Diastolic hypotension 
10066077 
Broad 
D 
9.1 
9.1 
Hypotension 
10021097 
Broad 
D 
8.1 
9.1 
Hypotensive crisis 
10083659 
Broad 
D 
23.0 
23.0 
Post procedural hypotension 
10084013 
Broad 
D 
23.0 
23.0 


FG-CLPLN-0010 
 
26-Apr-2021 18:54:34 GMT+0000 
Approval Task 
Verdict: Approve 
26-Apr-2021 19:45:49 GMT+0000 
Approval Task 
Verdict: Approve 
28-Apr-2021 00:32:57 GMT+0000 
Approval Task 
Verdict: Approve 
28-Apr-2021 00:52:26 GMT+0000 
Approval Task 
Verdict: Approve 
 
 
 
 
 
 
Document Approvals 
Approved Date(GMT-08:00): 03 May 2021 
 
 
 
Approval Task 
Verdict: Approve 
26-Apr-2021 19:15:40 GMT+0000 
 
 
 


FG-CLPLN-0010 
 
 
 
 
 
 
 
Document Approvals 
Approved Date(GMT-08:00): 03 May 2021 
 
 
Approval Task 
Verdict: Approve 
03-May-2021 15:39:26 GMT+0000