Clinical trial NCT04632940
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne Muscular Dystrophy, DMD Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Genetic Diseases, X-Linked
Sponsor: FibroGen
Start date: 2021-03-03; Completion date: 2023-12-14
Enrollment: 73 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids administered every 2 weeks in ambulatory participants with Duchenne muscular dystrophy (DMD) (age 6 to \<12 years).

Detailed description:
This is a global, randomized, double-blind, trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with DMD, aged 6 to \<12 years (ambulatory participants only). Approximately 70 participants will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic deflazacort or equivalent potency of corticosteroids administered orally) or Arm B (placebo+ systemic deflazacort or equivalent potency of corticosteroids administered orally), respectively. Randomization will be stratified by exon 44 deletion for analysis. Stratification has no impact upon treatment assignment nor dosage.

Participants must be fully informed of the potential benefits of approved products and make an informed decision when participating in a clinical trial in which they could be randomized to placebo.

The main study has 3 study periods:

* Screening period: Up to 4 weeks
* Treatment period: 52 weeks
* Safety Follow-up period/final assessment: A visit 28 days (+/- 3 Days) and a final safety follow-up phone call 60 days (+ 3 Days) after the last dose

Each participant will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks. Participants who complete 52 weeks of treatment may be eligible for an open-label extension (OLE), offering extended treatment with pamrevlumab.

Participants who discontinue study treatment for any reason should be encouraged to return to the investigative site to complete final safety and efficacy assessments.

Arms: arm 1: Pamrevlumab 35 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks arm 2: Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks
Interventions: intervention 1: Pamrevlumab intervention 2: Placebo intervention 3: Corticosteroids
Intervention descriptions: intervention 1: Pamrevlumab will be administered per dose and schedule specified in the arm description. intervention 2: Placebo will be administered per schedule specified in the arm description. intervention 3: Systemic deflazacort or equivalent potency of corticosteroids administered orally

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
STUDY TITLE: 
A Phase 3, Randomized, Double-Blind, Trial of 
Pamrevlumab (FG-3019) or Placebo in 
Combination with Systemic Corticosteroids in 
ambulatory subjects with Duchenne Muscular 
Dystrophy (DMD) 
PROTOCOL NUMBER: 
FGCL-3019-094 
PHASE: 
Phase 3  
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
KEY SPONSOR CONTACT(S): 
Name: 
 
Title: 
 
Mobile:  
 
E-mail Address: 
EUDRACT NUMBER: 
IND NUMBER: 
2020-000699-39 
126630 
STUDY DRUG: 
Pamrevlumab (FG-3019) 
INDICATION: 
Duchenne Muscular Dystrophy 
ORIGINAL PROTOCOL: 
Amendment 1: 
Amendment 2: 
Amendment 3: 
30 April 2020 
12 October 2020 
26 October 2020 
09 August 2021 
Amendment 4: 
28 October 2022 
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: NCT04632940


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INVESTIGATOR SIGNATURE PAGE 
STUDY ACKNOWLEDGEMENT 
 
A Phase 3, Randomized, Double-Blind, Trial of Pamrevlumab (FG-3019) or Placebo in 
Combination with Systemic Corticosteroids in Ambulatory Subjects with Duchenne Muscular 
Dystrophy (DMD) 
 
FGCL-3019-094 
Original: 30 April 2020 
Amendment 1: 12 October 2020 
Amendment 2:  26 October 2020 
Amendment 3: 09 August 2021 
Amendment 4: 28 October 2022 
 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and the current Investigator’s Brochure (IB), 
and I agree that it contains all necessary details for me and my staff to conduct this study as 
described. I will conduct this study as outlined herein and will make a reasonable effort to 
complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by FibroGen, Inc. I will discuss this material with them to ensure that they 
are fully informed about the drugs and the study. 
I will conduct the trial in accordance with the guidelines of Good Clinical Practice (GCP) 
including the archiving of essential documents, the Declaration of Helsinki, and any applicable 
local health authority, and Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) requirements. 
 
 
 
Investigator Name (Printed) 
 
Institution 
 
 
 
Signature 
 
Date 
Please return a copy of this signature page to FibroGen (or designee). Please retain the original 
for your study files. 


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CONFIRMATION OF PROTOCOL APPROVAL 
Original Protocol Date: 30 April 2020 
Amendment 1: 12 October 2020 
Amendment 2: 26 October 2020 
Amendment 3: 09 August 2021 
Amendment 4: 28 October 2022 
This protocol is approved by FibroGen. 
 
 
FibroGen, Inc. 
Date 
*See appended final page for 21CFR Part 11 compliant approval


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AMENDMENT 4.0: KEY CHANGES  
The protocol has been edited for clarity, consistency, and quality of content (typos, grammatical 
errors, etc.). A redline version documenting all changes from the previous version of this 
document is available upon request. 
Key Change 
Rationale 
Sections Affected 
In addition to the changes listed 
below, minor editorial changes were 
made throughout the document to 
improve consistency and clarity 
To correct typographical errors, 
and to improve consistency and 
clarity  
 
Throughout the document 
Removed “linearized” from 
NorthStar Ambulatory Assessment 
(NSAA) score 
The scoring of the NSAA will be 
clarified in the SAP 
 
Throughout the document 
Removed preliminary FGCL-3019-
079 data 
Completed FGCL-3019-079 
study results available and 
presented in last IB 
Section 2.5, Section 2.6 
Added bone fracture and height 
velocity safety assessments 
To align with the pediatric 
investigational plan 
Synopsis, Section 3.2.3, 
Appendix 1 Schedule of 
Assessments, Appendix 4 
Removed portion of inclusion 
criteria “Received pneumococcal 
vaccine (PPSV23) (or any other 
pneumococcal polysaccharide 
vaccine as per national 
recommendations) prior to study 
entry.”  
Modified this eligibility criteria into 
a recommendation instead of a 
requirement. Inserted language on 
vaccine recommendations for DMD 
patients based on national guidance.  
Vaccine recommendations vary 
by country and also depend on 
patient health status.  Due to 
this, FibroGen recommends 
patients be fully vaccinated 
against pneumococcal bacteria 
and influenza based on standard 
of care and national guidance, 
age and health status but does 
not enforce the requirement 
through eligibility criteria, nor 
which type of vaccine is 
required.    
Synopsis, Section 4.1, 6.1.1 


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Removed exclusion criteria 
“hypersensitivity reaction to 
Gadolinium-based Contracts Agents 
(GBCA) required for MRI 
acquisition.”  In addition, removed 
language pertaining to contract MRI. 
 
Prior to MRI, local laboratory 
assessments may be drawn at the 
discretion of the investigator.  The 
results of any local laboratory 
assessments are used to evaluate if it 
is safe for the subject to undergo the 
MRI with contrast.  These local 
laboratory results will not be 
captured in the clinical database 
Requirement for contrast MRI 
pertains only to the cardiac MRI 
which was removed in Protocol 
Amendment 3 
 
 
 
 
 
 
 
 
 
 
 
Synopsis, Section 4.2, 
6.2.3.1,  
Removed Genomics from specialty 
labs 
Clarification that Genomics is not 
collected in this study 
Schedule of Assessments   
Language regarding the end of 
infusion was added 
To clarify that the end of infusion 
is when the IP bag is empty.  Post-
flush is not included 
Section 5.1.6 
Clarified that medications for 
treatment of acute reactions, 
including anaphylaxis, are stored in 
a lockbox in the patient’s home for 
access by the Home Health Care 
nurse. 
Further clarification regarding the 
location of home health care 
medications 
Section 5.1.6, 5.1.7 
Removed language regarding 
destruction of partially used IP  
Used/partially used IP will be 
destroyed in reconstitution. 
Section 5.1.9 
Added language on where the 
COVID vaccinations should be 
captured in EDC 
Added for clarity on where 
vaccinations should be captured 
in EDC. 
Section 5.2.1 
Added preliminary non-clinical study 
results 
Preliminary results of rabbit 
embryo-fetal development study 
available to inform contraception 
recommendations 
Section 5.2.3 


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Collection of specific genetic DMD 
mutation  
To support characterization of 
most recent DMD mutation 
landscape and potentially 
evaluate possible relationships 
between patient genotype and 
clinical outcomes 
Section 6.1.1 
Added language regarding missed 
PFT and MFT assessments 
Added for clarity that missed 
PFT or MFTs should be 
conducted at the next scheduled 
visit or sooner if feasible. 
Section 6.1.4, 6.2.4 
Glomerular Filtration Rate (GFR) 
calculation language added 
Clarification that GFR is resulted 
by the central lab and the 
calculation that is used. 
Section 6.2.3.1 
Clarified height is collected at 
screening and Unscheduled visits 
and added height collection at Week 
52.  
Clarification added for 
assessments collected during 
vital signs examination at 
screening; height collection 
added for assessment of growth 
velocity 
Section 6.2.2 
Clarified videos of performance 
assessments will be sent for QC at 
certain visit weeks as well as when 
needed if required due to quality 
issues 
Added for clarity to further 
describe the on-going process 
functional testing quality 
control.     
Section 6.2.6 
LVEF% removed 
LVEF% capture pertains only to 
the cardiac MRI which was 
removed in Protocol 
Amendment 3 
Section 6.2.8.1 
Clarified China will not perform 
DMD video assessments 
Due to Regulatory guidelines 
this assessment will not be 
performed in China 
Section 6.2.8.2 
Additional PK, HAHA, HAHA-NA 
and immunogenic reaction blood 
draws 
To meet Regulatory 
recommendations for 
immunogenicity testing and to 
include local guidance to be 
followed for total blood volume. 
Section 6.2.3.1, 6.2.4.3, 
Appendix 2, Appendix 3 
Effect size, treatment difference, and 
common standard deviation revised 
in the Sample Size sections  
Numbers revised to reflect both 
the raw and linearized scales 
Synopsis, Section 8.1 


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Language added to Efficacy 
Analyses sections 
To further clarify the analyses 
to be used 
Sections 8.3.4.1, 8.3.4.2, 
8.3.4.2.4, and 8.3.4.2.5.1 
Language added regarding ATOM 
video QC  
Added to clarify the data 
collection, handling, and 
verification of video QC of the 
MFTs by study vendor ATOM 
Section 11.3, Section 6.2.6 
Removed “Weight” footnote as it 
already has a row in the SoA and 
added “Height” to the SoA 
For added clarity 
Appendix 1  Schedule of 
Assessments, Appendix 4 
OLE Schedule of 
Assessments 
Added clarification on starting week 
for patients entering the Open Label 
Extension portion of the trial and 
when End of Study visit takes place  
For added clarity  
Appendix 4 Open Label 
Extension  
Added timeframe of “within an 8 
week period” to the OLE missed 
doses language. 
To align with the main study 
Appendix 4 Open Label 
Extension 
Removed “Annual mean” from 
Ambulatory functional assessments 
To update the OLE endpoints 
Appendix 4 Open Label 
Extension 
 
 
 
 


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TABLE OF CONTENTS 
 
INVESTIGATOR SIGNATURE PAGE .........................................................................................2 
CONFIRMATION OF PROTOCOL APPROVAL.........................................................................3 
AMENDMENT 4.0: KEY CHANGES ...........................................................................................4 
LIST OF ABBREVIATIONS ........................................................................................................13 
1. 
PROTOCOL SYNOPSIS ...........................................................................................16 
2. 
INTRODUCTION ......................................................................................................22 
2.1. 
Description of Pamrevlumab ......................................................................................22 
2.2. 
Duchenne Muscular Dystrophy ..................................................................................22 
2.3. 
Connective Tissue Growth Factor ..............................................................................23 
2.4. 
Connective Tissue Growth Factor in Duchenne Muscular Dystrophy .......................24 
2.5. 
Clinical Trial Experience with Pamrevlumab .............................................................24 
2.6. 
Rationale and Risk/Benefit for Pamrevlumab in Duchenne Muscular 
Dystrophy ...................................................................................................................25 
2.6.1. 
Summary of Pamrevlumab Clinical Studies in DMD ................................................25 
2.6.2. 
Rationale for Efficacy Assessments ...........................................................................25 
2.6.3. 
Dose Rationale ............................................................................................................27 
2.6.4. 
Safety Summary ..........................................................................................................31 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................32 
3.1. 
Objective .....................................................................................................................32 
3.2. 
Endpoints ....................................................................................................................32 
3.2.1. 
Primary Endpoint ........................................................................................................32 
3.2.2. 
Secondary Endpoint ....................................................................................................32 
3.2.3. 
Safety Assessments .....................................................................................................32 
3.2.4. 
Exploratory Endpoint ..................................................................................................32 
3.2.5. 
Pharmacokinetics/pharmacodynamics (PK/PD) assessment ......................................32 
3.3. 
Overall Study Design ..................................................................................................33 
3.3.1. 
Study Duration ............................................................................................................33 
3.3.2. 
Placebo Control Group ...............................................................................................34 
3.4. 
Subject ID, Randomization and Treatment Assignment ............................................34 
3.4.1. 
Subject ID ...................................................................................................................34 
3.4.2. 
Randomization ............................................................................................................34 


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3.4.3. 
Treatment Assignment ................................................................................................34 
3.5. 
Blinding ......................................................................................................................35 
3.5.1. 
Maintenance of Blinding ............................................................................................35 
3.5.2. 
Request for Unblinding of Treatment Assignment .....................................................35 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................36 
4.1. 
Subject Inclusion Criteria ...........................................................................................36 
4.2. 
Subject Exclusion Criteria ..........................................................................................37 
4.3. 
Subject Withdrawal Criteria and Procedure ...............................................................38 
4.4. 
Replacement of Study Subjects ..................................................................................38 
4.5. 
Study Termination ......................................................................................................38 
5. 
TREATMENT OF SUBJECTS ..................................................................................39 
5.1. 
Study Treatment ..........................................................................................................39 
5.1.1. 
Pamrevlumab or Placebo ............................................................................................39 
5.1.2. 
Formulation .................................................................................................................39 
5.1.3. 
Study Drug Packaging and Labeling ..........................................................................39 
5.1.4. 
Study Drug Storage .....................................................................................................39 
5.1.5. 
Study Drug Preparation ..............................................................................................39 
5.1.6. 
Study Drug Administration.........................................................................................40 
5.1.7. 
Home Health Care (HHC) ..........................................................................................41 
5.1.8. 
Missed Dose ................................................................................................................41 
5.1.9. 
IP Handling and Disposal ...........................................................................................41 
5.2. 
Concomitant Medications ...........................................................................................42 
5.2.1. 
Permitted Concomitant Medications ..........................................................................42 
5.2.2. 
Prohibited Concomitant Medications .........................................................................42 
5.2.3. 
Contraception Requirements ......................................................................................43 
6. 
ASSESSMENTS OF EFFICACY ..............................................................................44 
6.1. 
Study Assessments......................................................................................................44 
6.1.1. 
Screening Period .........................................................................................................44 
6.1.2. 
Randomized Treatment Period ...................................................................................44 
6.1.3. 
End of Study/Safety Follow-up ..................................................................................45 
6.1.4. 
Missed Visits ..............................................................................................................45 
6.1.5. 
Unscheduled Visits .....................................................................................................45 


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6.2. 
If the subject is unable to perform MFTs at week 52 then the subject must 
have an unscheduled visit at the nearest possible date to perform MFTs 
Assessments ................................................................................................................45 
6.2.1. 
Vital Signs ..................................................................................................................45 
6.2.2. 
Vital signs are collected within 30 minutes before the infusion begins and 
again within 30 minutes after completion of IP infusion. Physical Exam 
(including Height and Weight) ...................................................................................46 
6.2.3. 
Laboratory Evaluations ...............................................................................................46 
6.2.4. 
Pharmacokinetics (PK) and Specialty Labs ................................................................48 
6.2.5. 
Local Pulmonary Function Test (PFT) .......................................................................49 
6.2.6. 
NorthStar Ambulatory Assessment (NSAA) ..............................................................49 
6.2.7. 
Other Functional Testing ............................................................................................50 
6.2.8. 
Exploratory Analysis ..................................................................................................50 
7. 
ASSESSMENT OF SAFETY .....................................................................................52 
7.1. 
Background .................................................................................................................52 
7.2. 
Definitions ..................................................................................................................52 
7.2.1. 
Definition of an Adverse Event (AE) .........................................................................52 
7.2.2. 
Definition of a Serious Adverse Event (SAE) ............................................................52 
7.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events ........................53 
7.3.1. 
Adverse Event Reporting Period ................................................................................53 
7.3.2. 
Adverse Event Eliciting/Reporting .............................................................................53 
7.3.3. 
Assessing Adverse Event Severity .............................................................................54 
7.3.4. 
Assessing the Adverse Event’s Relationship to IP .....................................................54 
7.3.5. 
Reporting Serious Adverse Events (SAEs) ................................................................55 
7.3.6. 
Pregnancies: Reporting and Follow-up of Female Partners of Subjects ....................56 
7.3.7. 
Abnormal Laboratory Findings ..................................................................................57 
7.3.8. 
Hypersensitivity/Anaphylactic Reactions: ..................................................................57 
7.3.9. 
Safety Monitoring .......................................................................................................57 
8. 
STATISTICS ..............................................................................................................59 
8.1. 
Sample Size Determination ........................................................................................59 
8.2. 
Analysis Populations ..................................................................................................59 
8.2.1. 
Intent to Treat (ITT) Population .................................................................................59 
8.2.2. 
Safety Population ........................................................................................................59 
8.3. 
Statistical Analysis ......................................................................................................59 
8.3.1. 
General Considerations ...............................................................................................59 


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8.3.2. 
Subject Enrollment and Disposition ...........................................................................60 
8.3.3. 
Demographics and Baseline Characteristics ...............................................................60 
8.3.4. 
Efficacy Analyses .......................................................................................................60 
8.3.5. 
Pharmacokinetic Analyses ..........................................................................................62 
8.3.6. 
Safety Analyses ..........................................................................................................62 
8.4. 
Statistical Analysis Plan .............................................................................................62 
9. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................63 
9.1. 
Data Quality Assurance ..............................................................................................63 
9.2. 
Audit and Inspection ...................................................................................................63 
10. 
ETHICS ......................................................................................................................64 
10.1. 
Ethical Considerations ................................................................................................64 
10.2. 
Communication with the Institutional Review Board or Independent Ethics 
Committee ...................................................................................................................64 
10.3. 
Subject Information and Consent ...............................................................................64 
10.4. 
Subject Confidentiality ...............................................................................................65 
11. 
DATA HANDLING AND RECORD KEEPING ......................................................66 
11.1. 
Source Documents ......................................................................................................66 
11.2. 
Direct Access to Source Documents...........................................................................66 
11.3. 
Data Collection, Handling, and Verification ..............................................................66 
11.4. 
Protocol Deviations ....................................................................................................67 
11.5. 
Retention of Data ........................................................................................................67 
11.6. 
Financial Disclosure ...................................................................................................67 
12. 
PUBLICATION POLICY ..........................................................................................68 
13. 
REFERENCES ...........................................................................................................69 
14. 
APPENDICES ............................................................................................................72 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................73 
APPENDIX 2. PHARMACOKINETIC AND PHARMACODYNAMIC SAMPLING ...........76 
APPENDIX 3. NORTHSTAR AMBULATORY ASSESSMENT (NSAA) ..............................77 
APPENDIX 4. OPEN LABEL EXTENSION (OLE) .................................................................79 
 
 
 
 


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LIST OF TABLES 
Table 1:  Pamrevlumab plasma exposures in male rats and DMD patients ……………………. 27 
Table 2:  PK parameters in study FGCL-3019-079 following a single dose .................................31 
Table 3:  Pamrevlumab (or placebo): Dose, Route, and Administration .......................................40 
 
LIST OF FIGURES 
Figure 1 
Study Scheme .............................................................................................................33 
 
 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
4SCV 
4-stair climb Velocity 
6MWD 
6-minute walking distance 
ADA 
anti-drug antibody 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ANCOVA 
analysis of covariance model 
ANCOVA-MI 
analysis of covariance model with Multiple Imputations 
AST 
aspartate aminotransferase 
AUC 
Area under the curve 
BMP 
bone morphogenetic protein 
BP 
Blood pressure 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CCN 
cellular communication network 
CMR 
cardiovascular magnetic resonance 
CNS 
central nervous system 
CPAP 
continuous positive airway pressure 
CRF 
case report form 
CRP 
C-reactive protein 
CS 
clinically significant 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTGF 
connective tissue growth factor 
DCM 
dilated cardiomyopathy 
DMC 
Data Monitoring Committee 
DMD 
Duchenne Muscular Dystrophy 
DN 
diabetic nephropathy 
ECG 
electrocardiogram 
ECM 
extracellular matrix 


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Abbreviation 
Definition 
EDC 
electronic data capture 
EMT 
epithelial mesenchymal transformation 
EOS 
End of Study 
ET 
Early Termination 
FEV1 
forced expiratory volume at 1 second 
FSGS 
focal segmental glomerulosclerosis 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
GCS 
Global Circumferential Strain 
GFR 
Glomerular filtration rate 
GGT 
gamma glutamyl transferase 
HAHA 
Human Anti-Human Antibody 
HHC 
Home Health Care 
HHM 
Hand Held Myometry 
HIPAA 
Health Insurance Portability and Accountability Act 
HSPG 
heparan sulfate proteoglycan 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G1 
IP 
investigational product 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IXRS 
Interactive Response System 
LF 
Liver fibrosis 
LGE 
Late Gadolinium Enhancement 
LoA 
Loss of Ambulation 
LRP 
Lipoprotein receptor-related protein 
LVEF 
Left ventricular ejection fraction 
LVEF % 
Left Ventricular Ejection Fraction percentage 


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Abbreviation 
Definition 
MAR 
Missing at random 
MNAR 
Missing not at random 
MRI 
Magnetic resonance imaging 
NCI 
National Cancer Institute 
NCS 
not clinically significant 
NSAID 
nonsteroidal anti-inflammatory drug 
OLE 
open-label, extension treatment 
OTC 
over-the-counter 
PDAC 
Pancreatic ductal adenocarcinoma 
PFT 
pulmonary function test 
PK/PD 
pharmacokinetics/pharmacodynamics 
PP 
Per protocol 
ppFVC 
percent predicted forced vital capacity 
ppPEF 
percent predicted peak expiratory flow 
PUL 
Performance of Upper Limb 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SOA 
Schedule of Assessment 
SPARC 
secreted protein acidic and rich in cysteine 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TTSTAND 
Time to stand 
ULN 
upper limit of normal 
WBC 
white blood cells 
WHODrug 
World Health Organization Drug 


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1. 
PROTOCOL SYNOPSIS 
Study Title: 
A Phase 3, Randomized, Double-Blind, Trial of Pamrevlumab (FG-
3019) or Placebo in Combination with Systemic Corticosteroids in 
Ambulatory Subjects with Duchenne Muscular Dystrophy 
Protocol Number: 
FGCL-3019- 094 
Investigational Product: 
Pamrevlumab (FG-3019) 
Study Phase: 
Phase 3 
Indication: 
Duchenne Muscular Dystrophy  
Number of Subjects 
Planned: 
Approximately 70 
Number of Sites Planned: 
Approximately 60 sites globally 
OBJECTIVES 
Study Objective:  To evaluate the efficacy and safety of pamrevlumab versus placebo in combination 
with systemic corticosteroids administered every two weeks in ambulatory subjects with Duchenne 
muscular dystrophy (age 6 to <12 years). 
ENDPOINTS 
Primary Endpoint: 
Ambulatory functional assessment:  
• Change in NorthStar Ambulatory Assessment (NSAA) total score from baseline to Week 52. 
Secondary Endpoints: 
Other Muscle function assessments:  
• Change in 4-stair climb Velocity (4SCV) assessment from baseline to Week 52.  
• Change in the 10-meter walk/run test from baseline to Week 52.  
• Changes in Time to Stand (TTSTAND) from baseline to Week 52.  
• Time to Loss of Ambulation (LoA) from baseline to Week 52 
 Exploratory Endpoint: 
• Change in Duchenne Video Assessment severity percentage from baseline to Week 52. 
• Change in ppFVC and ppPEF assessed by spirometry, from baseline to Week 52.  
 
    MRI Assessment: 
• Changes in lower extremities vastus lateralis muscle fibrosis score from baseline to Week 52, 
assessed by MRI. 


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Safety Assessments 
• 
All treatment emergent adverse events (TEAEs), serious adverse events (SAEs), clinically significant 
laboratory test abnormalities, discontinuation of treatment due to treatment-related AEs and 
hypersensitivity/anaphylactic reactions. 
• 
Number and percentage of subjects with hospitalizations due to any serious adverse events with 
pulmonary and/or cardiac cause(s). 
• 
Number and percentage of subjects with bone fractures 
• 
Annualized height velocity, HV (cm/year) from Baseline to Week 52   
Pharmacokinetics/pharmacodynamics (PK/PD) assessment 
• Population PK/PD analysis. 
STUDY DESIGN 
This is a global, randomized, double-blind, trial of pamrevlumab or placebo in combination with 
systemic corticosteroids in subjects with Duchenne muscular dystrophy, aged 6 to <12 years 
(ambulatory subjects only). Approximately 70 subjects will be randomized at a 1:1 ratio to Arm A 
(pamrevlumab + systemic deflazacort or equivalent potency of corticosteroids administered 
orally) or Arm B (placebo+ systemic deflazacort or equivalent potency of corticosteroids 
administered orally), respectively.  
 
 
• Randomization will be stratified by exon 44 deletion.  
Subjects who complete 52 weeks of treatment may be eligible to enter into the open-label, 
extension treatment (OLE) with pamrevlumab + systemic corticosteroids 
Arm A 
Arm B 
pamrevlumab 35 mg/kg IV Q2 weeks + 
systemic deflazacort or equivalent potency of 
corticosteroids administered orally 
matching placebo IV Q2 weeks + systemic 
deflazacort or equivalent potency of 
corticosteroids administered orally 
STUDY PERIODS 
Screening period: Up to 4 weeks 
Treatment period: 52 weeks (last dose on week 52) 
Efficacy Assessment Period (EAP): At Week 52 
Safety Follow-up period/End of Study (EOS): A visit 28 days (+/- 3 Days) and a final safety follow-up phone 
call 60 days (+ 3 Days) after the last dose 
Open label Extension (Appendix 4): Continued treatment with pamrevlumab 
 
 


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SUBJECT ELIGIBILITY CRITERIA 
UKey Inclusion Criteria 
Subjects must meet all of the following criteria in order to be eligible for the study: 
Age, and consent:  
1. Males at least 6 to <12 years of age at screening initiation 
2. Written consent by patient and/legal guardian as per regional/country and/or IRB/IEC 
requirements  
DMD diagnosis:  
3. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a 
validated genetic test.  
Pulmonary criteria: 
4. Average (of Screening and Day 0) percent predicted FVC above 45% 
5. On a stable dose of systemic corticosteroids for a minimum of 6 months, with no substantial 
change in dosage for a minimum of 3 months (except for adjustments for changes in body 
weight) prior to screening. Corticosteroid dosage should be in compliance with the DMD 
Care Considerations Working Group recommendations (e.g. prednisone or prednisolone 0.75 
mg/kg per day or deflazacort 0.9 mg/kg per day) or stable dose. A reasonable expectation is 
that dosage and dosing regimen would not change significantly for the duration of the study 
Performance criteria:  
6. Able to complete 6MWD test with a distance of at least 270M but no more than 450M on two 
occasions within 3 months prior to Randomization with ≤10% variation between these two 
tests. 
7. Able to rise (TTSTAND) from floor in <10 seconds (without aids/orthoses) at screening visit.  
8. Able to undergo MRI test for the lower extremities vastus lateralis muscle. 
Vaccination:  
9. Agreement to receive annual influenza vaccinations during the course of the study. 
Laboratory criteria: 
10. Adequate renal function: cystatin C ≤1.4 mg/L 
11. Adequate hematology and electrolytes parameters: 
a. Platelets >100,000/mcL 
b. Hemoglobin >12 g/dL 
c. Absolute neutrophil count >1500 /μL 
d. Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus (P) 
levels are within a clinically accepted range for DMD patients. 
12. Adequate hepatic function: 
a. No history or evidence of liver disease 
b. Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN) 


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c. Total bilirubin ≤1.5xULN 
UKey Exclusion Criteria 
Subjects must not meet any of the following criteria in order to be eligible: 
General Criteria: 
1. Concurrent illness other than DMD that can cause muscle weakness and/or impairment of 
motor function 
2. Severe intellectual impairment (eg, severe autism, severe cognitive impairment, severe 
behavioral disturbances) preventing the ability to perform study assessments in the 
Investigator’s judgment 
3. Previous exposure to pamrevlumab 
4. BMI ≥40 kg/m2 or weight >117 kg 
5. History of:  
a. allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal 
antibodies  
b. hypersensitivity to study drug or any component of study drug 
6. Exposure to any investigational drug (for DMD or not), in the 30 days prior to screening 
initiation or use of approved DMD therapies (e.g., eteplirsen (exondys 51), ataluren, 
golodirsen (vyondys 53), casimersen (amondys 45)) within 5 half-lives of screening, 
whichever is longer with the exception of the systemic corticosteroids, including deflazacort 
Pulmonary, Renal and Cardiac criteria: 
7. Requires ≥16 hours continuous ventilation 
8. Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis, 
emphysema, recurrent pneumonia that in the opinion of the investigator might impact 
respiratory function 
9. Hospitalization due to respiratory failure within the 8 weeks prior to screening 
10. Severe uncontrolled heart failure (NYHA Classes III-IV), or renal dysfunction, including any 
of the following: 
a. Need for intravenous diuretics or inotropic support within 8 weeks prior to screening 
b. Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to 
screening 
c. Patients with glomerular filtration rate (GFR) of less than 30 mL/min/1.73m2 or with 
other evidence of acute kidney injury as determined by investigator 
11. Arrhythmia requiring anti-arrhythmic therapy 
12. Any other evidence of clinically significant structural or functional heart abnormality 
Clinical judgment: 
13. The Investigator judges that the subject will be unable to fully participate in the study and 
complete it for any reason, including inability to comply with study procedures and treatment, 
or any other relevant medical, surgical or psychiatric conditions 


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STUDY TREATMENT 
UDose and Mode of Administration 
Pamrevlumab (or placebo):  35 mg/kg IV, Day 0 and every 2 weeks thereafter with the last dose at 
week 52. Subjects will receive up to 27 infusions over the course of the main study. 
Systemic Corticosteroids:  Systemic deflazacort or equivalent potency of corticosteroids 
administered orally 
STATISTICAL METHODS 
Sample Size Calculations: 
With a total sample size of 70 subjects allocated in a 1:1 ratio between the treatment arm and 
placebo, the study will achieve at least 80% power to detect an effect size of 0.705 (assuming a 
treatment difference of 6.0 points in linearized total NSAA with common standard deviation of 8.5, 
or a treatment difference of 1.91 in raw total NSAA with common standard deviation of 2.71) in the 
mean change from baseline in the total NSAA score with a one-sided significance level (alpha) of 
0.025.  
Statistical Analysis Methods: 
The primary endpoint, change in the total score of NSAA, from baseline to Week 52 will be analyzed 
using a Mixed Model for repeated Measure (MMRM) with treatment, visit, visit-by-treatment 
interaction, randomization stratification, and baseline total NSAA score. The primary analysis will be 
based on the ITT population.   
As sensitivity analysis, the analysis of covariance model (ANCOVA) model with Multiple 
Imputations (ANCOVA –MI) will be also applied. There will be 2 sets of multiple imputations 
performed for the missing data based on the two missing data pattern assumptions separately. One 
assumption of the missing data pattern is missing at random (MAR). Under the MAR assumption, 
the missing data after loss to follow-up will be imputed as continuing the trend of previously 
observed data, and this will be done separately for each treatment. The other missing pattern is 
missing not at random (MNAR).  Under the MNAR assumption, the missing data after loss to 
follow-up for the pamrevlumab subjects will be imputed as having the same data distribution as those 
in the placebo group, and the missing data of the placebo subjects will be imputed as continuing the 
trend of previously observed data. 
After a multiple imputation, the primary endpoint of change in the total score of NSAA will be 
calculated from the observed and imputed data and will be analyzed using analysis of covariance 
model (ANCOVA).  The ANCOVA model will include the same covariates as in the primary 
analysis. 
The model will include treatment, randomization stratification, and baseline total score of NSAA as 
covariates. The analysis will be based on the ITT population.   
For other secondary endpoints, as appropriate, Mixed Model for Repeated Measure (MMRM) / 
ANCOVA model will be used in continuous variables; logistic regression model in binary variables; 
Cox regression model in time-to-event variables. The analysis models will include appropriate 
baseline factors. Impact of missing data will be evaluated based on various assumptions. 


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Safety Analyses:  
All treatment-emergent adverse events (TEAEs) will be summarized by treatment arm, including: 
TEAEs Grade ≥3, treatment-emergent serious adverse events (TESAEs), deaths, and TEAEs leading 
to study or treatment discontinuation. Clinically significant changes from baseline in vital signs, 
laboratory tests will be summarized.  


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2. 
INTRODUCTION 
2.1. 
Description of Pamrevlumab 
Pamrevlumab is a recombinant fully human immunoglobulin G1 (IgG) kappa monoclonal 
antibody that binds to connective tissue growth factor (CTGF) and is being developed for 
treatment of diseases in which tissue fibrosis has a major pathogenic role, as 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. 
Duchenne Muscular Dystrophy 
Duchenne muscular dystrophy (DMD) is usually inherited in an X-linked recessive fashion, but 
it can occur as a result of spontaneous mutation in boys from families without a known history of 
the condition. On the basis of some 40 studies including several million male births, incidence at 
birth of Duchenne muscular dystrophy is around 1:3300, and its prevalence in the population (in 
terms of the total male population) is around 1:16500 (Emery1991). 
DMD is a result of mutations (mainly deletions) in the dystrophin gene (DMD; locus Xp21.2). 
Mutations lead to an absence of or defect in the protein dystrophin, which results in progressive 
muscle degeneration with loss of independent ambulation by the age of 13 years (Bushby 2010). 
In skeletal muscles of DMD patients constant myofiber breakdown results in persistent activation 
of myofibroblasts and altered production of extracellular matrix (ECM) resulting in extensive 
fibrosis. Muscle fibrosis is the only myo-pathologic parameter that significantly correlated with 
poor motor outcome as assessed by quadriceps muscle strength, manual muscle testing of upper 
and lower limbs, and age at ambulation loss (Desguerre 2009). 
Patients with DMD are generally wheelchair bound before they develop significant respiratory 
muscle weakness. Respiratory complications are the primary cause of morbidity and mortality in 
DMD as progressive respiratory muscle weakness leads to hypoventilation and/or recurrent 
atelectasis and pneumonia, secondary to decreased cough effectiveness (McKim 2012). 
The clinical signs of DMD develop at a young age; first clinical symptoms are usually reported 
before the age of 5 years (Annexstad 2014, Pane 2013). Female carriers are most often 
asymptomatic but may demonstrate mild symptoms and are susceptible to cardiomyopathies 
(Bushby 2003, Yiu 2015) 
The principal clinical characteristic of DMD is signs of muscle weakness and wasting. Affected 
children will have difficulties with jumping, running, climbing stairs or rising from the floor due 
to progressive limb weakness. By the age of 12, they will lose their independent ambulation and 
become wheelchair-bound (Annexstad 2014; Tsuda 2018; Zhou 2010). Major clinical signs of 
DMD patients are respiratory impairment, and cardiac dysfunction, leading to multiple organ 
disabilities and are ultimately the leading cause of morbidity and mortality in patients with 
DMD.   Respiratory manifestations include respiratory muscle weakness, obstructive sleep 
apnoea, mucus plugging and respiratory failure (Birnkrant 2018). After age 10 to 14, patients 
gradually begin to lose respiratory muscle function based on pulmonary function tests (PFTs) 
such as forced vital capacity (FVC). The median loss in FVC (% predicted) is estimated to be 
8.0% per year (Phillips 2001; Tangsrud 2001). 


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Dystrophin deficiency in the heart causes cardiomyopathies which are later responsible for 
cardiac complications. With the progression of the disease, the myocardium fails to meet 
physiological demands and clinical manifestations of heart failure occur such as fatigue, weight 
loss, vomiting, abdominal pain, sleep disturbance and inability to operate daily activities 
(Birnkrant 2018). Because of improvements in respiratory care, cardiac dysfunction is now a 
leading cause of morbidity and mortality in DMD patients (Schram 2013). Progressive 
myocardial fibrosis, as detected by late gadolinium enhancement (LGE), is strongly correlated 
with the left ventricular ejection fraction (LVEF) decline in Duchenne muscular dystrophy 
patients. Longer steroid treatment duration is associated with a lower age-related increase in 
myocardial fibrosis burden (Tandon 2015). 
Boys treated for DMD have low-trauma extremity fractures as a result of osteoporosis, and 30% 
may develop symptomatic vertebral and leg fractures due to bone fragility. Osteoporosis is a side 
effect of glucocorticoid therapy. Those bone manifestations can lead to chronic back pain, spine 
deformity, bone fractures, scoliosis and premature or permanent loss of ambulation (Birnkrant 
2018). As dystrophin is also expressed in the central nervous system (CNS), other clinical 
manifestations of DMD patients are neuropsychological problems, and neurobehavioral 
abnormalities (Annexstad 2014; Tsuda 2018; Zhou 2010). Endocrine disturbances also occur in 
part of adolescents with DMD. Those hormonal disorders provoke a delay in the age of puberty 
and short stature problems (Annexstad 2014; Leung 2011; Zhou 2010). 
Maximal life-expectancy of DMD patients is currently estimated at 30–40 years of age (Walter 
2017). Corticosteroid treatment and higher standards of medical care such as artificial respirators 
have considerably improved survival within the last two decades (Birnkrant 2018; Bushby 2010; 
Falzarano 2015; van Westering 2015; Wu 2014). 
2.3. 
Connective Tissue Growth Factor 
Connective tissue growth factor is a 38 kDa secreted matricellular glycoprotein of the cysteine-
rich 61/CTGF/nephroblastoma overexpression (aka cellular communication network [CCN]) 
family (Perbal 2004; Rachfal 2005). It is produced by many cells, including fibroblasts, 
myofibroblasts, endothelial cells, mesangial cells, and stellate cells. The name “connective tissue 
growth factor” implies a mechanism of action similar to that of classic growth factors, which 
signal through specific cell-surface receptors. However, experimental evidence indicates that 
CTGF, and the other members of the CCN family, have activities associated with matricellular 
proteins that function in a more subtle modulatory fashion. Matricellular proteins are a subclass 
of ECM proteins that modulate cellular functions and signaling pathways through multiple 
mechanisms that depend on cell type and the cellular context. Prototypical representatives of this 
subclass include secreted protein acidic and rich in cysteine (SPARC), osteopontin, and 
thrombospondins (Bornstein 2002). Connective tissue growth factor fits squarely within this 
group of proteins, is generally expressed at high levels during development and in response to 
injury, and typically binds to multiple cell-surface receptors, ECM components, growth factors, 
and cytokines (Chen 2009). The cellular functions that can be modulated by CTGF include 
secretion and/or organization of ECM, cell proliferation, survival, adhesion, migration, and 
epithelial mesenchymal transformation (EMT). Modulation of cellular signaling appears to occur 
through interactions of CTGF with 1) cell surface components such as integrins or the low 
density lipoprotein receptor-related protein (LRP)-1 (a multifunctional endocytic and signaling 
receptor), 2) cytokines and cytokine inhibitors, and 3) matrix components such as heparan sulfate 
proteoglycans (HSPGs) and fibronectin. Interactions with HSPGs may displace other HSPG-


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binding proteins such as VEGF and bone morphogenetic proteins (BMPs). Binding of cytokines 
to CTGF may either sequester them in an inactive conformation, or help to present cytokine 
binding partners to their receptors.  
2.4. 
Connective Tissue Growth Factor in Duchenne Muscular Dystrophy 
Connective tissue growth factor is a nonstructural regulatory protein present in the ECM that has 
an important role in fibrosis. Skeletal muscle from DMD patients, dystrophic dogs, and mdx 
mice all show elevated levels of CTGF (Porter 2003; Sun 2008). 
Connective tissue growth factor can reproduce or amplify the effects of TGF-ß on fibrosis by 
inducing collagen type 1, α5 integrin, and fibronectin much more potently than TGF-ß in 
fibroblasts (Kharraz 2014). 
Comparison of mdx mice with normal or genetically depleted levels of CTGF revealed that 
exercised mice with reduced CTGF developed less fibrosis and exhibited better muscle strength 
than mice with normal levels of CTGF (Morales 2013). In culture, both myoblasts and myotubes 
were shown to express and secrete CTGF into the medium, and respond to the CTGF by 
increasing the ECM constituents, partially inhibiting myoblast differentiation and inducing 
myoblast dedifferentiation (Vial 2008). 
In DMD, the role of CTGF might extend well beyond replacement fibrosis secondary to loss of 
muscle fibers, since its transient overexpression upon adenovirus injection into skeletal muscle 
induced a transient dystrophic-like phenotype (Morales 2011) and antibody inhibition of CTGF 
enabled better engraftment of satellite cells (Morales 2013). 
A major manifestation of DMD is cardiac fibrosis. Cardiac fibrosis is associated with increased 
CTGF expression in the mdx mouse heart. Connective tissue growth factor may be a key 
mediator of early and persistent fibrosis in dystrophic cardiomyopathy (Au 2011). 
Connective tissue growth factor is critically involved in several chronic fibro degenerative 
diseases. Pamrevlumab treatment has been shown to positively affect the course of several of 
these diseases in Phase 1 and Phase 2 clinical studies. 
Together, these observations suggest that CTGF may play an important role in DMD and thus, 
inhibition of CTGF function by pamrevlumab could result in decreased fibrosis in the muscles 
and possibly increased muscle function. 
2.5. 
Clinical Trial Experience with Pamrevlumab 
The clinical trial experience with pamrevlumab includes 11 clinical studies across a number of 
indications, including DMD that are presented in the current Investigator’s Brochure. 
Overall, pamrevlumab has been well tolerated. The duration of exposure by indication is 
displayed in the current Investigator’s Brochure. 
Adverse events (AEs) have been generally mild or moderate in severity and transient in duration.  
The AEs have been typical of the subjects’ underlying medical condition(s). Infusions of 
pamrevlumab have been well tolerated. There is no apparent pattern to the serious adverse events 
(SAEs) observed during these clinical trials. 
Refer to the Investigator’s Brochure for additional information. 


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2.6. 
Rationale and Risk/Benefit for Pamrevlumab in Duchenne Muscular Dystrophy 
The rationale and positive risk/benefit ratio for the 093 study originates in the literature and 
preliminary safety and efficacy data of the 079 main study, now complete. Please refer to the 
current Investigator’s Brochure for detailed information. 
2.6.1. Summary of Pamrevlumab Clinical Studies in DMD  
 
Study Number 
Study Title or Description 
Country 
N  
Status 
Target age 
of 
population 
Duchenne Muscular Dystrophy 
 
FGCL-3019-079 
A Phase 2, Open-Label- Study to 
Evaluate the Safety, Tolerability, 
and Efficacy of pamrevlumab in 
Non-Ambulatory Subjects with 
DMD 
USA 
21 
Main 
study: 
(Complete) 
OLE:  
(Ongoing) 
 
12 years 
and older 
FGCL-3019-093 
A Phase 3, Randomized, Double-
Blind, Trial of Pamrevlumab (FG-
3019) or Placebo in Combination 
with Systemic Corticosteroids in 
Subjects with Non-ambulatory 
Duchenne Muscular Dystrophy 
(DMD) 
Global 
90  
Ongoing  
12 years 
and older 
FGCL-3019-094 
A Phase 3, Randomized, Double-
Blind, Trial of Pamrevlumab (FG-
3019) or Placebo in Combination 
with Systemic Corticosteroids in 
Subjects with ambulatory 
Duchenne Muscular Dystrophy 
(DMD) 
Global 
70 
Ongoing 
6 < 12 
years of 
age 
 
2.6.2. Rationale for Efficacy Assessments 
2.6.2.1. 
Pulmonary Assessments: 
2.6.2.1.1. Forced Vital Capacity (FVC): 
Pulmonary dysfunction in DMD is progressive and restrictive in nature and is one of the most 
common causes of morbidity and mortality in non-ambulatory patients. Forced vital capacity 
(FVC) assessed by spirometry, is the best global assessment of all respiratory muscles, because it 
requires a full inspiration (reflecting function of inspiratory muscles) and a full expiration 


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(reflecting function of expiratory muscles) (Finder, 2017). Pulmonary function tests have an 
excellent feasibility (defined as the percent of subjects able to perform the task) of > 95% in 
non-ambulatory DMD patients (Connolly, 2015). With the widespread use of corticosteroids, a 
delay in pulmonary function decline by 2-3 years has been observed. However, once patients are 
in the decline phase, a similar rate of decline has been observed regardless of glucocorticoid 
treatment. Several studies have shown that rates of decline are similar for both steroid- and 
non-steroid treated patients with DMD once in the decline phase (Mayer, 2015); (Connolly, 
2015); (McDonald, 2018a). 
Natural history data show that non-steroid and steroid users aged 10 to 18 years had similar 
changes (decline) in FVC% of 5% to 6% per year (Ricotti, 2019), (Finder, 2017), (Mayer, 2015). 
2.6.2.1.2. Forced Expiratory Volume at 1 Second (FEV1): 
FEV1 assesses airway function and is the standard global assessment in both clinical and 
research studies of asthma, chronic obstructive pulmonary disease, and cystic fibrosis. FEV1 is 
understood to correlate closely with FVC, with the advantage of requiring less prolonged effort 
(1 second). (Finder, 2017). Data from the placebo group, in the DELOS study (Buyse, 2015) 
have shown that yearly rates of ppFEV1 decline were -10.2% [SD 2.0] (Meier, 2017). 
2.6.2.1.3. Peak Expiratory Flow Rate (PEFR): 
Expiratory flows are easily measured and predominantly reflect expiratory muscle function. Full 
inspiration is needed to achieve maximal flow; therefore Peak Expiratory Flow Rate (PEFR) 
requires both inspiratory and expiratory muscle function (Finder, 2017). The annual rate of 
change for ppPEFR was −5.8 ± 0.6%/year (mean ± SE) based on prospective data in DMD 
patients, collected in the Neuromuscular Clinic at The Children’s Hospital of Philadelphia 
(Philadelphia, PA) from 2005–2010 (Mayer, 2015). In a more recent publication, the 1-year 
change in ppPEFR was -4.8% (Ricotti, 2019) with N=29. 
2.6.2.2. 
Muscle Function 
See section 6.2.6. 
2.6.2.2.1. Fibrosis and FAT assessment of the Upper Arm (Biceps brachii) assessed by 
MRI: 
In the recent years, several longitudinal studies have reported the potential value of MRI as a 
biomarker to assess disease progression and treatment effect in DMD. MRI biomarkers provide 
the advantage of studying different muscle groups in both lower and upper limbs, enabling 
assessment of disease progression in not only ambulant, but also non-ambulant patients 
incapable of performing physical tests, in addition to being an objective measure not influenced 
by patient’s motivation during functional tests (Szigyarto, 2018). 
T2-mapping can help determine the level of inflammation, edema and fat infiltration present in 
the affected muscle (Magrath, 2018). 
Overall the preliminary results from the ongoing phase 2 study in non-ambulatory DMD subjects 
show that pamrevlumab may have a beneficial effect on several clinically meaningful parameters 
affecting the DMD population.  Pamrevlumab, as an antifibrotic agent, has shown the potential 
to slow disease progression in patients with DMD.  That, in addition to being well tolerated in 
pediatric patients is considered of significant clinical benefit. Therefore, the risk-benefit ratio 


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remain favorable. For more information please reference the current Investigator’s Brochure. 
Additionally, to date there has been no important identified risk to this study population (age 6 to 
<12) vs the non-ambulatory population, aged 12 years and above. 
2.6.3. Dose Rationale 
The nonclinical safety of pamrevlumab has been evaluated in three juvenile toxicity studies in 
Sprague Dawley rats.   FibroGen has conducted a 2-week non-GLP and a 1-month GLP study 
initiated in postnatal day (PND) 21 rats and a non-GLP 2-week tolerability study initiated in 
PND 7 rats.   
To date pamrevlumab has been well tolerated at all doses tested in all nonclinical safety studies 
conducted with no pamrevlumab-related target organ toxicities observed in the GLP repeated 
dose toxicity studies in adult animals to support general development of pamrevlumab or in the 
GLP toxicity study conducted in juvenile rats (PND 21) in support of the pediatric indication. 
There was a pamrevlumab-related increase in prostate weights in PND 21 rats at the high dose 
(100 mg/kg) in the 2-week dose range finding (DRF) study (FibroGen Study No. 352015011) at 
a rat/human exposure ratio (AUC) of 2.2 compared to the DMD clinical study (Study FGCL-
3019-079). The No Observed Adverse Effect Level (NOAEL) in this 2-week DRF study was 30 
mg/kg with an exposure ratio (AUC) of 0.6 (Table 1).  However, this prostate effect was not 
reproduced at the NOAEL of 200 loading dose/100 mg/kg maintenance doses in the subsequent 
GLP 4-week study (352016001). In this 4-week study, PND 21 rats received 9 doses of 
pamrevlumab over 4 weeks as opposed to 4 administrations of pamrevlumab over 2 weeks in the 
DRF study resulting in similar exposure (AUC) ratio of 2.2 at the NOAEL (Table 1).  In 
addition, pamrevlumab was well tolerated in a 2-week tolerability study when administered to 
PND 7 rats at doses of 50 and 200 mg/kg TIW for 4 weeks resulting in an exposure ratio at the 
NOAEL (200 mg/kg) of 4.6, with a trend of decreased body weight and body weight gain at 50 
and 200 mg/kg (Table 1). However, these body weight effects were not considered adverse, as 
they were not dose related and appeared to rebound during the recovery period.   
 
Table 1. Pamrevlumab plasma exposures in male rats and DMD patients  
 
Study Type 
(Study 
Number) 
High 
Dose 
(mg/kg)  
and 
Regimen 
 
Cmax 
(µg/mL) 
 
AUC 
(hr*µg/mL) 
 
Cmax ratio 
(Rat/Human) 
 
AUC ratioa 
(Rat/human) 
2-week 
Juvenile Rat 
DRF 
(352015011) 
30 
(NOAEL) 
523 
32000 
0.5 
0.6 
100 
2X/week 
1805 
118000 
1.9 
2.2 
1-month 
Juvenile Rat 
GLP 
(352016001) 
200/100 
2X/week 
(NOAEL) 
1805b 
118000b 
1.9b 
2.2b 


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2-week 
Juvenile Rat 
Tolerability 
DRF 
(352020009) 
200 
3Xweek 
(NOAEL) 
4660 
163000 
4.8 
4.6 
DMD 
Clinical 
Study 
(FGCL-
3019-079) 
35 
Once 
every two 
weeks 
970 
212000 
NA 
NA 
aAUC ratios include a "correction factor" of 6 (Q2W in clinic vs three-times-weekly in rats) or 4 (Q2W in clinic vs. 
three times weekly in rats) 
bestimated conservatively based on 2-week Juvenile Rat DRF study (352015011). Full TK was not conducted in this study; 
presence of pamrevluamb was evaluated in plasma samples collected on PND 50, 24 hours after the final dose and on PND 77 
after recovery. 
Together, the totality of the nonclinical safety data for pamrevlumab in juvenile rats suggest the 
35 mg/kg dose of pamrevlumab administered every 2 weeks proposed for the non-ambulatory 
patients old DMD patients >12 years would be well tolerated in patients < 12 years of age. 
To date, there is no clinical data available for subjects who are 6-<12 years old. FibroGen is 
planning to share all available clinical data upon completion of study 094 for ambulatory DMD 
subjects, in the future.  
2.6.3.1. 
Pharmacokinetics 
The PK parameters of pamrevlumab have been evaluated in subjects with idiopathic pulmonary 
fibrosis (studies FGCL-MC3019-002 and FGCL-3019-049), subjects with pancreatic cancer 
(Study FGCL-MC3019-028), and subjects with diabetic nephropathy (Study FGCL-3019-
MC003). PK data in DMD subjects are available from the ongoing study 079. Study results are 
summarized below. 
2.6.3.2. 
Single-Dose Idiopathic Pulmonary Fibrosis Study FGCL-MC3019-002 
Pharmacokinetics parameters of pamrevlumab were evaluated in 21 subjects receiving single 
dose intravenous infusions of 1, 3, and 10 mg/kg pamrevlumab over at least 120 minutes. Cmax 
(µg/ml) values were: 24.58, 123.7 and 274.8 for the three doses respectively. Tmax was 2 hours 
in all groups. AUC (µg.h/ml) values were: 2181, 13280 and 33190 respectively for the three 
doses.  
Globally, the AUC and Cmax increased with the dose over the studied dose range. The plasma 
elimination rate for pamrevlumab slowed with dose increase, suggesting that a saturable process 
may be involved in pamrevlumab elimination. Both one-compartment and two-compartment PK 
models adequately described the elimination phase after a single pamrevlumab infusion. The 3 
mg/kg cohort exhibited a lower effective volume of distribution as a percentage of body weight, 
leading to a higher Cmax than would be expected on the basis of normalized dose. This 
difference in the 3 mg/kg cohort may be due to the increased mean body mass index in this group 
(approximately 34 kg/mP2
P, compared to 29 kg/mP2
P in other cohorts). 


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2.6.3.3. 
 Single and Multiple-dose PK in Subjects with Incipient Nephropathy Due to 
Type 1 or Type 2 Diabetes Mellitus (FGCL-3019-MC003) 
Single dose: The PK of pamrevlumab after administration of single doses of 3 and 10 mg/kg was 
evaluated in 23 subjects with incipient nephropathy due to type 1 or type 2 diabetes mellitus (PK 
report Study FGCL-MC3019-003). In general, the AUC and Cmax increased more-than-
proportionally to dose over the dose range in this study. Mean t½ was 73 and 141 hr at 3 and 10 
mg/kg respectively. Considering the variability among the individuals and between studies, the 
clearance and volume of distribution values appeared to be comparable between the different 
subject populations at comparable pamrevlumab doses. 
Multiple dose: The PK of pamrevlumab after administration of multiple IV doses of 3 and 10 
mg/kg was evaluated in 18 subjects with incipient nephropathy due to type 1 or type 2 diabetes 
mellitus (PK report Study FGCL-MC3019-003). Cmax at Day 0 was 72.9 ± 20.9 in the group 
receiving 3 mg/kg and 420 ± 211 in the group receiving 10 mg/kg. Tmax(h) at day 0 was: 2.25 in 
the 3mg/kg group and 3.04 in the 10mg/kg group. Mean t½ at day 0 was 73.3±16.8 and 
141±25.3 at 3 and 10 mg/kg respectively. At day 42, Cmax values were: 76.0 ± 11.1 in the 3 
mg/kg group and 511 ± 310 in the 10 mg/kg group. Tmax values recorded at day 42 were 
respectively 4.12 and 6 in the two doses groups. In general, the AUC and Cmax also increased 
more-than-proportionally to dose over the studied dose range. Mean t½ at day 42 was 102 and 
135 hr at 3 and 10 mg/kg respectively, indicating the same trend of increasing t½ with this 
comparable dose range that was observed in other studies. There was a decrease in systemic 
clearance values between Day 0 versus Day 42 and an increase in exposure following repeated 
dosing compared to the exposure after single (first) dose, which is expected based on the t½ and 
the Q2W dosing interval. A comparison of trough levels (Day 42 versus Day 56) suggested that 
steady state had been reached before Day 42, which is consistent with the t½ values. 
2.6.3.4. 
 Multiple-Dose Idiopathic Pulmonary Fibrosis Study FGCL-3019-049 
Plasma PK of pamrevlumab after administration of multiple doses of 15 and 30 mg/kg every 3 
weeks (Q3W) was evaluated as an exploratory endpoint in Study FGCL-3019-049 which 
enrolled 89 subjects with idiopathic pulmonary fibrosis. Cmax (μg/ml) mean values reported 
after the 1st, 9th, and 16th doses were respectively 332±85, 349±106 and 324±134 at the 15 
mg/kg dose. Cmax (μg/ml) mean values reported after the 1st, 9th, and 16th doses were 
respectively 815±219, 860±207 and 804±165 at the 30 mg/kg dose. Cmin (μg/ml) mean values 
after the 1st, 9th, and 16th doses were respectively 21±9, 39±24 and 44±24 at the 15 mg/kg dose. 
Cmin mean values after the 1st, 9th, and 16th doses were respectively 99±44, 217±115 and 
174±80 at the 30 mg/kg dose.  
Overall, Cmax and Cmin values were consistent with those at similar time points of comparable 
doses in previous studies. Cmax and Cmin increased with increasing dose from 15 mg/kg to 30 
mg/kg.  
There was a general trend of increasing Cmax and Cmin with repeated dosing from first dose to 
9th or 16th dose, which is consistent with the t½ of pamrevlumab and dosing regimen of once 
Q3W. With a plasma t½ of approximately 1 week (determined from previous studies), the steady 
state was expected be reached after several doses (i.e., by the 9th dose). This is generally 
consistent with the observed PK data in this study. For example, the comparable mean/median 
Cmin and Cmax values at 9th and 16th doses for Cohort 2 (30 mg/kg) were slightly higher than 
those at Day 1. For Cohort 1 (15 mg/kg), the mean/median Cmax values at 16th dose time point 


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was slightly lower than those on 1st and 9th dose. However, the decrease was probably due to a 
reduction in the number of subjects at 16th dose time point and an increase in Cmax variability, 
rather than an actual decrease in exposure over repeated dosing (from 9th to 16th dose). 
PK sampling was conducted at only 2 time points (post-dose and pre-dose) between doses, so t½ 
estimates were not available from this study.  
2.6.3.5. 
Multiple-Dose Pancreatic Cancer Study FGCL-MC3019-028 
In Study FGCL-MC3019-028, 75 subjects with pancreatic cancer were enrolled. Pamrevlumab 
was administered in combination with gemcitabine/erlotinib. Plasma PK of pamrevlumab was 
evaluated as a secondary endpoint after administration of multiple doses. Six cohorts were dosed 
at 3, 10, 15, 25, 35, or 45 mg/kg Q2W, and 2 cohorts dosed weekly at either 35 mg/kg on Day 1 
followed by 17.5 mg/kg weekly or 45 mg/kg on Day 1 followed by 22.5 mg/kg weekly. 
Based on the available pamrevlumab plasma-concentration data:  
• CRmin
R and CRmax
R values increased with increasing dose. Analysis of CRmax
R indicated that 
increases were dose proportional.  
• CRmin
R and CRmax
R values generally increased with repeated dosing, which is consistent 
with the dosing regimens and tR½
R of pamrevlumab.  
• Pamrevlumab exposure (based on estimated AUC values) generally increased with 
increasing dose.  
• Overall, CRmin
R and CRmax
R values were comparable to those at similar doses in previous 
studies. 
• On Day 1, TRmax
R was 3 hours from the start of dosing and 1 hour from the end of the 
infusion. On Day 43, TRmax
R was 2 hours from the start of dosing and 1 hour from the 
end of the infusion. 
• After the first dose, the estimated median tR½ 
Rincreased from 2.4 days for the 3 mg/kg 
dose to 4.5-8 days for doses ≥10 mg/kg. After repeated dosing (on Day 43), the 
estimated median tR1/2
R increased from 2.6 days for the 3 mg/kg dose to 6.6–9.0 days 
for doses ≥10 mg/kg. 
• Estimated tR½
R values for doses >10 mg/kg did not appear to increase markedly with 
dose, based on available data (limited time points) averaging to approximately 1 
week, (the highest 2 dose regimens [35 and 45 mg/kg every two weeks] showed a 
median value of 7.85 and 7.29 days, respectively).  
2.6.3.6. 
Single/multiple Dose PK in DMD subjects in Study FGCL-3019-079 
Pharmacokinetic sampling was conducted in study FGCL-3019-079, where DMD subjects were 
dosed with 35 mg/kg pamrevlumab once every 2 weeks. PK samples were collected at predose, 
<1h after end of infusion, and on Days 2, 4, 7, 10 and 14 following the first dose, as well as at 
steady-state at weeks 26 and 52 (predose at both times, and post dose at week 52). Pamrevlumab 
concentrations were measured in all plasma samples. After preliminary PK analysis (NCA) 
based on preliminary concentration-time profiles of each individual, the PK parameters from this 
study (Table 2) appeared to be comparable to those obtained from previous PK studies (study 
FGCL-MC3019-002 and study FGCL-3019-MC003; respectively), suggesting that the 
pamrevlumab exposures in pediatric DMD subjects were comparable to those in adults, without 


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any marked exposure/PK difference between various disease of patient populations, which were 
shown in dose-justification analysis by population PK/PD exploration. 
Table 2:  PK parameters in study FGCL-3019-079 following a single dose 
TRmax 
CRmax 
AUCRt 
AUCR0-∞ 
tR1/2 
CL 
VRz 
VRss 
(hr) 
(µg/mL) 
(hr*µg/mL) 
(hr*µg/mL) 
(day) 
(mL/hr/kg) 
(mL/kg) 
(mL/kg) 
Mean 
2.73 
970 
145000 
212000 
8.77 
0.174 
52.1 
50.6 
SD 
0.756 
307 
34000 
49200 
1.83 
0.0427 
15.2 
14.7 
Median 
2.68 
904 
144000 
215000 
8.76 
0.163 
50.2 
48.0 
2.6.4. Safety Summary 
Overall, pamrevlumab appears to be well-tolerated. As of the data cutoff date, 1723 subjects 
have received study drug  (pamrevlumab or placebo) in the pamrevlumab clinical program 
including both completed and ongoing studies (1036 subjects in studies that are blinded at the 
time of this IB) comprising 420 subjects with pancreatic cancer, 829 subjects with IPF, 112 
subjects with liver fibrosis secondary to hepatitis B, 20 subjects with COVID-19, 190 pediatric 
subjects with DMD, 107 subjects with diabetic neuropathy (DN), 2 pediatric subjects with focal 
segmental glomerulosclerosis (FSGS), and 43 healthy subjects. For additional information on the 
safety of pamrevlumab in the completed DMD study (079) and other indications, please refer to 
the current version of the Investigator’s Brochure.  


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3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Objective 
To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with 
systemic corticosteroids administered every two weeks in ambulatory subjects with Duchenne 
muscular dystrophy (age 6 to <12 years). 
3.2. 
Endpoints 
3.2.1. Primary Endpoint 
Ambulatory functional assessment:  
• 
Change in North Star Ambulatory Assessment (NSAA) total score from baseline to 
Week 52. 
3.2.2. Secondary Endpoint 
Other functional assessments:  
• Change in 4-stair climb Velocity (4SCV) assessment from baseline to Week 52.  
• Change in the 10-meter walk/run test from baseline to Week 52.  
• Changes in Time to Stand (TTSTAND) from baseline to Week 52. 
• Time to Loss of Ambulation (LoA) from baseline to Week 52   
3.2.3. Safety Assessments 
• All treatment emergent adverse events (TEAEs), serious adverse events (SAEs), 
clinically significant laboratory test abnormalities, discontinuation of treatment due to 
treatment-related AEs and hypersensitivity/anaphylactic reactions. 
• Number and percentage of subjects with hospitalizations due to any serious adverse 
events with pulmonary and/or cardiac cause(s). 
• Number and percentage of subjects with bone fractures. 
• Annualized height velocity, HV (cm/year) from Baseline to Week 52   
3.2.4. Exploratory Endpoint  
• Change in Duchenne Video Assessment severity percentage from baseline to Week 
52. 
• Change in ppFVC and ppPEF assessed by spirometry, from baseline to Week 52,  
     MRI Muscle assessment: 
• Changes in lower extremities vastus lateralis muscle fibrosis score from baseline to 
Week 52, assessed by MRI  
3.2.5. Pharmacokinetics/pharmacodynamics (PK/PD) assessment 
• Population PK/PD analysis. 


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3.3. 
Overall Study Design 
This is a Phase 3, randomized, double-blind, placebo-controlled multi-center trial to evaluate the 
efficacy and safety of pamrevlumab in ambulatory subjects with DMD over a 52 week period.   
Subjects must be fully informed of the potential benefits of approved products and make an 
informed decision when participating in a clinical trial in which they could be randomized to 
placebo.   
Approximately 70 subjects will be enrolled in this trial, globally.  Subjects will be randomized in 
a 1:1 ratio to one of the two study treatment arms; pamrevlumab or placebo. Randomization will 
be stratified by exon 44 deletion.    
The main study has three study periods: 
• Screening period: Up to 4 weeks 
• Treatment period: 52 weeks  
• Safety Follow-up period/final assessment:  A visit 28 days (+/- 3 Days) and a final 
safety follow-up phone call 60 days (+ 3 Days) after the last dose 
Each subject will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 
weeks.  Subjects who complete 52 weeks of treatment may be eligible for an open-label 
extension (OLE), offering extended treatment with pamrevlumab.    
Subjects who discontinue study treatment for any reason should be encouraged to return to the 
investigative site to complete final safety and efficacy assessments. 
Figure 1 
Study Scheme 
  
 
 
Abbreviations: EOS= End of Study, ET=Early Termination 
a) Subjects who discontinue the study early, for any reason, will complete an early termination visit 28 days (+/- 3 
Days) and a final safety follow-up phone call 60 days (+ 3 days) after the last infusion.   
3.3.1. Study Duration 
All subjects are encouraged to complete up to 27 doses of study treatment, an End of Study 
(EOS)/Safety follow-up visit 28 days (+/- 3 Days) and a final safety follow-up phone call 60 


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days (+ 3 Days) after the last dose.  Subjects, who discontinue the study early, for any reason, 
will need to come in for an early termination visit (ET) 28 days (+/- 3 Days) and a final safety 
follow-up phone call 60 days (+ 3 Days) after the last infusion. If a patient withdraws from the 
study after randomization and prior to dosing, an ET visit and safety follow-up phone call are not 
required. See also Section 4.3 for mandatory discontinuation reasons, and for procedures related 
to the ET. 
Subjects who complete the study may be eligible for rollover into an open-label, extension, 
which will provide data on the long-term safety and efficacy of pamrevlumab.   
End of trial is defined as the date at which the last subject completes the final safety follow-up 
phone call. 
3.3.2. Placebo Control Group 
In order to evaluate the effect of treatment with pamrevlumab approximately 50% of subjects 
will be randomized to placebo treatment. 
For DMD subjects one of the only treatment options is systemic corticosteroids. Therefore, 
placebo control, given with systemic corticosteroids, is appropriate and ethical. All study 
subjects who are eligible, including those randomized to placebo and who complete the study, 
will be given the option to crossover to the active arm in the open label extension, which will 
provide data on the long-term safety and efficacy of pamrevlumab.   
3.4. 
Subject ID, Randomization and Treatment Assignment 
3.4.1. Subject ID 
All subjects will be assigned an 8 digit subject ID number consisting of a four digit site number 
and a 4 digit subject ID starting with 
. Subject numbering will be assigned sequentially per 
site as subjects are recruited/screened (e.g., 
, 
, and 
, etc.). The first subject enrolled 
at each site will have a subject ID of 
. 
3.4.2. Randomization  
Approximately 70 subjects will be randomized 1:1 to receive either pamrevlumab or placebo, 
resulting in approximately 35 subjects in treatment arm A and 35 subjects in treatment arm B.  
Each subject will receive a unique 3 digit randomization code. 
Randomization schedules will be prospectively prepared.  Automated randomization and 
treatment assignments will be performed by an Interactive Response System (IXRS or IRT).   
Randomization will be stratified by exon 44 deletion (Yes/No) for analysis. Stratification 
has no impact upon treatment assignment nor dosage.    
3.4.3. Treatment Assignment 
Subjects will be randomized 1:1 to one of two treatment arms: 
Arm A 
Arm B 
pamrevlumab 35 mg/kg IV Q2 weeks + 
systemic deflazacort or equivalent potency 
of corticosteroids administered orally 
matching placebo IV Q2 weeks + systemic 
deflazacort or equivalent potency of 
corticosteroids administered orally 


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3.5. 
Blinding 
This is a double-blind, placebo-controlled study. The Investigator, study site staff, subjects, 
selected sponsor clinical team and designees are blinded to study drug assignment. Blinded 
treatment with a placebo control is the gold standard method for obtaining unbiased assessments 
of safety and efficacy in clinical trials of investigational drugs such as pamrevlumab. 
3.5.1. Maintenance of Blinding 
The study blind will be maintained for all parties specified above throughout the study.  
Pamrevlumab and placebo will be identical in appearance, packaging, and labeling in order to 
maintain the study blind. The blind will remain intact even while subject rollover into the open 
label extension and until the database is locked for the main study.  
3.5.2. 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.  FibroGen 
approval is not a prerequisite for the investigator to unblind a subject.  It is the responsibility of 
the investigator to promptly document and notify the Sponsor of any unblinding.   
The IRT system allows authorized users to break the blind for a specific subject.  Detailed 
instructions for unblinding are provided in the IRT user manual. 
 


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4. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1. 
Subject Inclusion Criteria 
In order to be eligible for inclusion in this trial, a subject must meet all of the following: 
Age, Consent: 
1. Males at least 6 to < 12 years of age, at screening initiation  
2. Written consent by patient and/or legal guardian as per regional/ country and/or IRB/IEC 
requirements  
DMD Diagnosis: 
3. Medical history includes diagnosis of DMD and confirmed Duchenne mutation, 
including status of exon 44 using a validated genetic test 
Pulmonary criteria: 
4. Average (of Screening and Day 0) percent predicted FVC above 45% 
5. On a stable dose of systemic corticosteroids for a minimum of 6 months, with no 
substantial change in dosage for a minimum of 3 months (except for adjustments for 
changes in body weight) prior to screening. Corticosteroid dosage should be in 
compliance with the DMD Care Considerations Working Group recommendations (e.g. 
prednisone or prednisolone 0.75 mg/kg per day or deflazacort 0.9 mg/kg per day) or 
stable dose. A reasonable expectation is that dosage and dosing regimen would not 
change significantly for the duration of the study.  
Performance criteria:  
6. Able to complete 6MWD test with a distance of at least 270 M but no more than 450 M 
on two occasions within 3 months prior to Randomization with ≤10% variation between 
these two tests. 
7. Able to rise (TTSTAND) from floor in <10 seconds (without aids/orthoses) at screening 
visit.  
8. Able to undergo MRI test for the lower extremities vastus lateralis muscle. 
Vaccination:  
9. Agreement to receive annual influenza vaccinations during the conduct of the study. 
Laboratory criteria: 
10. Adequate renal function: cystatin C ≤1.4 mg/L 
11. Adequate hematology and electrolytes parameters: 
a. Platelets >100,000/mcL 
b. Hemoglobin >12 g/dL 
c. Absolute neutrophil count >1500 /μL 
d. Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus 
(P) levels are within a clinically accepted range for DMD patients. 


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12. Adequate hepatic function: 
a. No history or evidence of liver disease 
b. Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN) 
c. Total bilirubin ≤1.5xULN 
4.2. 
Subject Exclusion Criteria 
Subjects must not meet any of the following criteria in order to be eligible: 
General criteria: 
1. Concurrent illness other than DMD that can cause muscle weakness and/or impairment of 
motor function 
2. Severe intellectual impairment (eg, severe autism, severe cognitive impairment, severe 
behavioral disturbances) preventing the ability to perform study assessments in the 
Investigator’s judgment 
3. Previous exposure to pamrevlumab 
4. BMI ≥40 kg/mP2
P or weight >117 kg 
5. History of: 
a. allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies 
b. hypersensitivity to study drug or any component of study drug 
6. Exposure to any investigational drug (for DMD or not), in the 30 days prior to screening 
initiation or use of approved DMD therapies (e.g., eteplirsen (exondys 51), ataluren, 
golodirsen (vyondys 53), casimersen (amondys 45)) within 5 half-lives of screening, 
whichever is longer with the exception of the systemic corticosteroids, including 
deflazacort 
Pulmonary, Renal, and Cardiac criteria: 
7. Requires ≥16 hours continuous ventilation 
8. Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis, 
emphysema, recurrent pneumonia that in the opinion of the investigator might impact 
respiratory function 
9. Hospitalization due to respiratory failure within the 8 weeks prior to screening 
10. Severe uncontrolled heart failure (NYHA Classes III-IV), or renal dysfunction, including 
any of the following: 
a. Need for intravenous diuretics or inotropic support within 8 weeks prior to screening 
b. Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to 
screening 
c. Patients with glomerular filtration rate (GFR) of less than 30 mL/min/1.73m2 or with 
other evidence of acute kidney injury as determined by investigator 
11. Arrhythmia requiring anti-arrhythmic therapy 
12. Any other evidence of clinically significant structural or functional heart abnormality 


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13. Clinical judgement: The Investigator judges that the subject will be unable to fully 
participate in the study and complete it for any reason, including inability to comply with 
study procedures and treatment, or any other relevant medical, surgical or psychiatric 
conditions 
4.3. 
 Subject Withdrawal Criteria and Procedure 
Subjects may withdraw from the study at any time, for any reason. If a subject or investigator 
determines subject should discontinue from treatment, the subject has the option to remain on 
study.  If the subject remains on study, they should continue to perform on-study assessments 
until the end of study visit or subject terminates for one of the below reasons.    
Reasons for withdrawing the subject from the study include the following:  
• Any safety concern in the Investigator’s opinion, that precludes further study 
participation 
− Pamrevlumab will be permanently discontinued in case of serious or life-
threatening allergic reactions 
• Major protocol deviation to inclusion/exclusion that substantially affects subject 
safety  
• Withdrawal of Consent (reason of withdrawal should be obtained) 
Subjects who discontinue the study early will complete an Early Termination visit 28 days (+/- 3 
days) and complete a final safety follow-up phone call 60 days (+3 Days) after the last infusion. 
If subject is randomized but not dosed with IP before Early Termination on Day 0, an Early 
Termination visit is not required.   
Note: At the Early Termination visit, MFTs (NSAA, 4-Stair Climb Velocity, 10M Walk/Run, 
Time to Stand, and Loss of Ambulation (LOA) assessment) should be conducted.  MRI does not 
have to be repeated if the last one was performed within 4 weeks of this visit.  
4.4. 
Replacement of Study Subjects 
All randomized subjects will be included in the study. Subjects who discontinued the study early 
will not be replaced.  
4.5. 
Study Termination 
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 a study by FibroGen 
may include (but are not limited to): 
• Successful completion of the study at the investigational site 
• The required number of subjects for the study has been recruited 
• Failure of the Investigator to comply with the protocol, GCP guidelines or local 
requirements 
• Safety concerns 
• Inadequate recruitment of subjects by the Investigator  


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5. 
TREATMENT OF SUBJECTS 
5.1. 
Study Treatment 
5.1.1. Pamrevlumab or Placebo 
Pamrevlumab is a fully human IgG1 kappa monoclonal antibody that binds to CTGF and is 
formulated as a solution for administration by IV infusion.  Peripheral or central venous access 
may be utilized at the discretion of the investigator. 
Matching placebo is formulated as a solution to be administered in a manner that is identical to 
pamrevlumab infusion. 
5.1.2. Formulation 
Pamrevlumab is supplied in single-use glass vials containing sterile, preservative-free solution 
(100 mg pamrevlumab/vial or 500 mg pamrevlumab/vial respectively).  The solution is 
composed of 10 mg/mL pamrevlumab, 1.60 mg/mL L-histidine, 3.08 mg/mL L-histidine HCl, 
8.01 mg/mL sodium chloride, and 0.05 mg/mL polysorbate 20, resulting in a solution with a 
tonicity of approximately 290 mmol/kg and a pH of 6.0.   
The placebo formulation is of identical composition as the pamrevlumab formulation, except for 
the absence of pamrevlumab. 
5.1.3. Study Drug Packaging and Labeling 
Labels will be prepared and will comply with Good Manufacturing Practice requirements for 
labelling and local regulatory guidelines.   
5.1.4. Study Drug Storage 
Vials of pamrevlumab and placebo must be stored refrigerated (2°C to 8°C), in a temperature- 
controlled and monitored environment, protected from light, and in a securely locked area to 
which access is limited to appropriate study personnel. Documentation of the storage conditions 
must be maintained by the site for the entire period of study participation. Details regarding the 
reporting of temperature excursions can be found in the study Investigational Product (IP) 
Manual. 
5.1.5. Study Drug Preparation 
Pamrevlumab or placebo is infused undiluted after pooling the contents of the calculated number 
of vials in an empty infusion bag (Utotal volume of fluid must not exceed 410 mL)U according to 
the Dose Preparation Instructions in the IP Manual. 
Pamrevlumab and placebo solutions for infusion must be refrigerated (2˚C to 8˚C) and 
administered within 48 hours of preparation and within 6 hours if left at room temperature after 
preparation.  Pamrevlumab or placebo infusion solutions are administered by IV infusion 
(peripheral or central venous access), using an infusion set with a 0.2 µm in-line filter.  Gravity 
infusion or use of an infusion pump are both acceptable methods of infusion as per local 
institutional standards. 


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5.1.6. Study Drug Administration 
Dosing for pamrevlumab (or placebo) will be based on the weight obtained at screening and 
approximately every 12-weeks after Day 0. The total dose of pamrevlumab (or placebo) is not to 
exceed 4.1g.  Subjects weighing more than 117 kg will receive the maximum allowable dose of 
4.1g.  The dose should be prepared in a volume of fluid that does not exceed 410 mL. IP will be 
administered after release from the site’s pharmacy (or central pharmacy for sites in the United 
States utilizing home health care) and infused within 48 hours of preparation as long as it is 
stored from 2-8C after preparation, otherwise, drug should be infused within 6 hours of 
preparation if stored at room temperature. 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 dose, route, infusion rate and schedule for the administration of pamrevlumab or 
placebo is provided in Table 3. 
Table 3:  Pamrevlumab (or placebo): Dose, Route, and Administration 
Agent 
Dose 
Route 
Infusion Rate 
Frequency 
Pamrevlumab 
(or placebo) 
35 
mg/kg 
IV 
Not to exceed 150 
cc/hour* 
Every 2 weeks (+/- 3 
days) 
 
 
Note:  DO NOT ADMINISTER STUDY DRUG AS AN IV PUSH OR BOLUS 
INJECTION, OR CONCURRENTLY IN THE IV LINE WITH OTHER AGENTS. 
*Gravity infusion or use of an infusion pump are both acceptable methods of infusion as per local institutional 
standards. 
Adjustments may be made to further slow the rate of infusion to less than 150 cc/hour in 
accordance with the investigator’s clinical judgement. 
The Investigator or a designee with proper medical training must be either present, or 
immediately available, during the first Study Drug infusion and observation period 
(approximately 1 hour after the end of IP infusion) 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. If a subject experiences a significant infusion reaction and continues 
Study Drug dosing, a physician should be immediately available during all subsequent infusions 
and observation periods at the site. If the Investigator wishes to use premedication, (e.g., 
antihistamines, nonsteroidal anti-inflammatory drugs (NSAIDs)) for a subsequent infusion, this 
should be discussed with the FibroGen Medical Monitor or designee.  
Infusions are to be continued until the total volume of the IP infusion has been administered. 
Subjects will remain at the study site for 1 hour after the end of the IP infusion for clinical 
observation for all study infusions.  
IP will be administered at a hospital or ambulatory setting with adequate facilities for managing 
medical emergencies. Medications for the treatment of acute reactions, including anaphylaxis, 
must be available to study site staff for immediate use. Medications for the treatment of acute 
reactions, including anaphylaxis, will accompany the HHC nurse.  
The Sponsor may consider the use of properly trained HHC staff to administer the infusions of 
study drugs at the subject’s home and corresponding study assessments during the conduct of the 
study (after the completion of three infusions without safety concerns), consistent with 
institutional regulations and policies (see Section 5.1.7 for details). Medication for the treatment 


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of acute reactions, including anaphylaxis, will be available at the subject’s home for access by 
the home health care (HHC) nurse. 
There is no specific treatment for a pamrevlumab overdose or infusion reaction. Signs and 
symptoms should be managed with appropriate standard of care treatment. 
5.1.7. Home Health Care (HHC) 
HHC may be available to some subjects and will be a decision driven by a combination of the 
request from the study site, the availability of qualified service in the subject’s country, the 
needs/circumstances of the subject, and Sponsor decision on overall feasibility. Subjects who 
have previously experienced an infusion reaction will not be allowed to participate in HHC. 
Medications for the treatment of acute reactions, including anaphylaxis, are required to be 
available in the patient’s home for all IP administration visits. The pharmacy is required to 
dispense anaphylaxis medication for the first home visit, as the HCP will store it in a lockbox in 
the patient’s home until the end of the study. Following any adverse reaction at an HHC visit, the 
subject should speak to the study doctor and make a visit, if needed.  The subject should also 
have his next scheduled infusion performed on site until the investigator deems it safe for the 
subject to return to home infusions.  HHC support will only be on weeks where no other 
assessments besides infusions are being completed. PI maintains overall responsibility for patient 
careand their participation in the study.  The HHC vendor requires PI signature on the PI 
Oversight Form, which outlines each GCP PI oversight responsibility and the supporting HHC 
vendor process. The Sponsor maintains oversight of the HHC vendor. 
5.1.8. Missed Dose 
Every attempt should be made to complete all study visits within window.   
Visit dates are scheduled based on the previous visits, not the baseline visit. Protocol-defined 
visits conducted outside the ± 3 day study visit window will be recorded as a protocol deviation. 
Missed doses are not to be made up through extra visits. If a subject misses more than two 
infusions in any 8-week period throughout the study, or two sequential infusions, the FibroGen 
Medical Monitor should be notified.  The reason for missed doses must be documented in the 
subject’s clinical record. 
Refer to the case report form (CRF) completion guidelines in the Study Reference Manual for 
additional information on CRF completion requirements for missed visits.  
5.1.9. IP Handling and Disposal 
All IP provided by the Sponsor should be retained at the site until otherwise instructed in writing 
by the Sponsor (or designee). If local/regional/institutional policies do not allow the site to retain 
IP, the site must provide the sponsor (or designee) their drug destruction SOP/process for review 
and approval. The Sponsor (or designee) will perform IP accountability and reconciliation for all 
IP received at the site prior to approving IP return/destruction. Upon completion of 
accountability/reconciliation or upon completion of the study or termination of the 
investigational site, all unused, IP, and all IP that was not dispensed will be shipped to a 
destruction site designated by the Sponsor (or designee) for destruction. IV bags used to infuse 
study drug can be disposed of per institutional policy. Please refer to the IP Manual for 
additional information on study drug materials, management and accountability.   


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5.2. 
Concomitant Medications 
5.2.1. Permitted Concomitant Medications 
Concomitant medications (any prescription and/or over-the-counter [OTC] preparation) and 
procedures or nondrug therapies (e.g., physical therapy, acupuncture, continuous positive airway 
pressure [CPAP]) used by a subject while participating in this clinical trial must be recorded 
from Screening Visit through the End-of-Study (EOS) Visit.  
Other than the restrictions that follow, concomitant medications may be given at the discretion of 
the Investigator. It is expected that Investigators will provide optimal medical management of 
DMD and that subjects may be treated with concomitant medications for their various medical 
conditions. Optimal medical care must be provided, and Investigators should ensure, for 
example, that subjects maintain stable vital signs and laboratory test values during the course of 
the study. 
Oral systemic corticosteroids or deflazacort are required, and must be recorded in the clinical 
chart and the CRF.  
There are no safety concerns anticipated with the co-administration of pamrevlumab and 
COVID-19 vaccine.  However, FibroGen recommends a time separation between the 
administration of a COVID-19 vaccine and blinded study drug (pamrevlumab or placebo) of at 
least 48 hours to allow for better interpretation of any adverse events and their relationship to the 
vaccine or study drug. All adverse events should be reported to FibroGen per protocol. 
The date of any vaccination administered from the time of screening until the end of the study 
must be reported in the Concomitant Medications CRF. COVID vaccinations should be captured 
in the Medical History section of EDC if administered prior to consent. COVID vaccination 
while on study should be entered into the Concomitant Medication CRF.   
5.2.2. Prohibited Concomitant Medications 
Concomitant medications and therapies that can interfere with a) the course of DMD, b) the 
protocol endpoint assessments or, c) the study treatments, will not be allowed during the study. 
Some justified exceptions may apply. 
Prohibited medications include any other (approved or investigational) agents for the treatment 
of DMD. The list of prohibited concomitant medications for treatment of DMD includes, but is 
not limited to, the following:  
• eteplirsen (EXONDYS 51) 
• ataluren 
• golodirsen (VYONDYS 53) 
• Viltolarsen (Viltepso) 
• Casimersen (AMONDYS 45) 
Questions about concomitant medications should be discussed with the FibroGen Medical 
Monitor or designee.  Patients who are on any approved therapy for DMD should not discontinue 
the therapy to be eligible for the 094 study.  However, if their approved therapy is discontinued 
for other reasons, they could be considered for participation in this study if they meet all 
eligibility criteria. 


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Study drug should not be administered to subjects with a history of allergic or anaphylactic 
reaction to human, humanized, or chimeric monoclonal antibodies. 
5.2.3. Contraception Requirements  
A non-clinical study evaluating the potential effects of pamrevlumab on embryo-fetal 
development has been conducted (rabbit embryo-fetal development study 352021017). 
Preliminary results show the pamrevlumab systemic exposure levels at 200 mg/kg to the 
pregnant female rabbits which resulted in fetal external and skeletal abnormalities are 
approximately 20-fold greater than the systemic exposure levels in humans at doses of 30mg/kg 
or 35 mg/kg in our current protocols. 
No adverse effects of pamrevlumab administration were observed in a study of rat male and 
female fertility.   
Recognizing the age range for this study, male subjects who have partners with reproductive 
potential are required to use contraception (condoms per Clinical Trial Facilitation Group 
(CTFG) recommendation version 1.1 21-09-2020, Section 2.3) during the conduct of the study 
and for 12 weeks (3 months) after the last dose of study drug. Permitted contraceptive methods 
for the subjects include use of a condom (per Clinical Trial Facilitation Group (CTFG) 
recommendation version 1.1 21-09-2020, Section 2.3) or sexual abstinence during treatment. 
Sexual abstinence is considered a highly effective method only if definedas refraining from 
heterosexual intercourse during the entire period of risk associated with IP. The reliability of 
sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject.   The package insert regarding reproductive risks 
associated with the use of corticosteroids used in this study should be evaluated and reviewed 
with the subject, if applicable. 


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6. 
ASSESSMENTS OF EFFICACY 
6.1. 
Study Assessments 
A signed and dated IRB/IEC-approved informed consent must be obtained before any study-
specific assessments are performed. Assessments that are part of routine care are not considered 
study-specific and may be used at screening to determine eligibility. All subjects will be 
screened for eligibility before randomization. Only eligible subjects will be randomized into the 
study.  
NOTE: In accordance with FDA/ EMA Guidance: During the COVID-19 pandemic, the visit 
modality (e.g.: in-person versus remotely) and scheduling maybe adjusted and conducted at the 
discretion of the Investigator, in accordance with the site’s rules and recommendations, and 
using all necessary precautions. If a visit has to be done remotely, it can be conducted with any 
technology available to the site and study subjects, such as via tele-health visits, phone calls, etc. 
6.1.1. Screening Period 
All screening procedures must be performed within 28 days of signing the ICF. Lead times for 
scheduling MRI may dictate timing of consenting subjects to maintain a 28 day window.  Study 
procedures to be performed during the screening period can be found in the Schedule of 
Assessments (SOA).  Subjects may have a specific procedure such as labs or PFTs repeated 
during screening to determine if the subject can enter the study. If the subject does not meet 
eligibility criteria, they must be screen failed.  If the investigator feels that the assessments that 
resulted in screen failure did not adequately represent the subject’s eligibility for the study, the 
subject may be re-screened at the discretion of the investigator.  Repeating procedures within the 
screening window, or screen failing and rescreening a subject should be discussed with the 
medical monitor to evaluate which procedures should be repeated and when. 
Each subject’s specific DMD genetic mutation should be entered in the EDC under medical 
history.  
Due to the immunocompromised status of DMD patients, it is recommended the pneumococcal 
vaccine is administered as per national recommendations and standard of care for Duchenne 
Muscular Dystrophy patients on corticosteroids prior to study entry.   
This vaccination recommendation can be met by administration of any applicable pneumococcal 
vaccine as per national guidance.   This includes both conjugate (PCV13) and polysaccharide 
(PPSV23) vaccines.   Patients should also agree to receive annual influenza vaccinations during 
the course of the study as needed. 
6.1.2. Randomized Treatment Period 
The Randomized Treatment Phase begins on Day 0 (first infusion of Study Drug) and continues 
through Week 52. Visit windows are within ± 3 days of the scheduled visit date (14 days from 
prior visit).  Visit dates should be scheduled based on the previous visit, not the baseline visit. 
Subjects who complete 52 weeks of treatment may be eligible to rollover into the OLE study 
where all subjects will be treated with pamrevlumab.  If a subject discontinues the main study 
early for any reason, they will not be eligible for inclusion in the OLE. 


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6.1.3. End of Study/Safety Follow-up 
All subjects enrolled will have an EOS/safety follow-up visit 28 days (± 3 Days) and a final 
safety follow-up phone call at 60 days (+3 days) after the last dose of study treatment.  After the 
protocol-required reporting period (60 days (+ 3 Days) after the last dose), the investigator does 
not need to actively monitor subjects for SAEs.  However, if the investigator becomes aware of 
an SAE/death that may be possibly related to study treatment after the protocol-required 
reporting period, the investigator may report the event to FibroGen. SAEs reported outside of the 
protocol-required reporting period will be captured within the safety database only as clinical 
trial cases for the purposes of expedited reporting 
6.1.4. Missed Visits 
Visit dates are scheduled based on the previous visits, not the baseline visit. Protocol-defined 
visits conducted outside the ± 3 day study visit window will be recorded as a protocol 
deviation. For missed visits, the subject will be asked to resume the planned visit schedule and 
return for the next scheduled visit. 
6.1.5. Unscheduled Visits 
Unscheduled visits/assessments may be required at the discretion of the investigator.  
Unscheduled visit data will be captured accordingly in the clinical database. 
Subjects who, in the judgment of the PFT or MFT technician or investigator, are unable to 
perform MFTs ((NSAA, 4-Stair Climb Velocity, 10M Walk/Run, Time to Stand, Loss of 
Ambulation (LoA assessment)) adequately on a scheduled visit should repeat PFT or MFT 
assessment as soon as possible, or at minimum ensure to complete PFT or MFTs assessment at 
the next scheduled visit.  
6.2. 
If the subject is unable to perform MFTs at week 52 then the subject 
must have an unscheduled visit at the nearest possible date to 
perform MFTs Assessments 
Refer to the SOA (16TAppendix 16T) for the main study and Appendix 4 for the OLE study for details 
regarding the timing and frequency of study assessments.  Laboratory evaluations, muscle 
function tests should be performed prior to infusions.   
6.2.1. Vital Signs 
Vital signs to be collected include; heart rate, blood pressure, respirations and temperature:   
• Heart rate should be collected as beats/min 
• Respiration rate should be collected as breaths per minute 
• Systolic and diastolic blood pressure should be collected from subjects in seated 
position (mmHg) 
• Temperature should be taken as oral or tympanic or using any standard method and 
captured as °F or °C 


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6.2.2. Vital signs are collected within 30 minutes before the infusion begins and again 
within 30 minutes after completion of IP infusion. Physical Exam (including Height 
and Weight) 
A full physical exam is required at screening, throughout the treatment period, and at EOT, EOS 
or ET.   
•  Height is collected at Screening, Week 52, preferably by the same trained person. 
The height measurement should be taken standing against a wall if possible, with a 
standard height measurement tool (such as a wall-mounted calibrated stadiometer).  
• Weight is collected during screening, Week 12, and every 12 weeks (or within 14 
days prior) thereafter for dosing adjustment 
6.2.3. Laboratory Evaluations 
Details regarding sample collection, preparation and transport can be found in the central lab 
manual.   
6.2.3.1. 
Central Lab Testing 
Central lab results obtained during the screening period will be used to determine subject 
eligibility for participation in the trial.   
Central lab results will be reviewed by the investigator for clinical significance and to determine 
appropriate reporting of adverse events.   
 NOTE: Local laboratory assessments may be used in case of Central Laboratory supply 
shortages or shipment delays. If local laboratory assessments are used instead of central labs, 
results will be entered into the clinical database, and the following points need to be considered: 
• In case of local screening labs, the Investigator needs to review the results with 
respect to protocol specified Laboratory Inclusion Criteria for adequate renal 
function, adequate hematology and electrolytes parameters, and adequate hepatic 
function. 
• For on-study laboratory assessments, only laboratory abnormalities that are 
considered clinically significant in the Investigator’s assessment need to be reported 
as TEAEs, as per Protocol Section 7.3.7. In such a case, if possible, the etiology of a 
lab abnormality should be reported as TEAE, not the abnormal lab value. 
• For collecting specialty lab samples at a local laboratory: 
o HAHA and HAHA-NA samples should be collected according to the schedule of 
assessments using local supplies while processing/storing these samples as 
described in the ICON lab manual.  
 HAHA and HAHA-NA samples may be stored at the clinical site and 
batch shipped to ICON  
 Other specialty samples (PK) will not be required if local labs are being 
used 


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The following labs will be evaluated by a central laboratory: 
The maximum total for any blood draw visit is about 1.8 tablespoons 26ml/visit.  An additional 
1.4 teaspoons (20ml) will be drawn in the event of an immunogenic reaction (see Section 
6.2.4.3 for more details)   
The total amount of blood drawn throughout the entire study is less than the maximum allowable 
volume per subject/visit according to recommendations in the article Ethical considerations for 
clinical trials on medicinal products with minors (September 2017).  
Local guidelines and regulations on total blood volume to be drawn within a certain time frame 
takes precedence over this generalized recommendation. 
NOTE: For example 
•
If a subject’s weight is under 30kg, the additional PK blood draw should not be
collected.
•
If the subject’s weight is under 20kg, the additional PK, HAHA, and HAHA-NA
blood draws should not be collected.
Glomerular Filtration Rate (GFR) is calculated and resulted by the central lab contracted by the 
Sponsor for Exclusion Criteria 10c.  For subjects 18 years old and under, the “Creatinine – Cystatin 
C based CKiD equation (Schwartz 2012)” is used. However, it is common for patients with DMD 
to have very low creatinine to the level where it is below detectable limits and a result cannot be 
reported.  As a result, GFR may or may not be available to support the evaluation of acute kidney 
injury.  Other tests and diagnostic tools for assessment by the investigator should be used in this 
instance. 


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CBC: 
Chemistry Panel: 
Absolute neutrophil count (ANC) 
BUN 
Eosinophils 
Creatine Kinase 
RBCs (Erythrocyte count) 
Creatinine 
Hematocrit % 
Chloride 
Hemoglobin 
Magnesium 
WBCs (Leukocyte count) 
ALP 
Lymphocytes 
ALT 
Monocytes 
AST 
Neutrophils 
Bilirubin, total 
Platelets 
Albumin 
CRP 
Phosphorous 
Basophils 
Potassium 
Sodium 
GGT 
  Calcium 
  GFR 
  Cystatin-C 
Abbreviations:         ALP = alkaline phosphatase; ALT = alanine aminotransferase; 
AST = aspartate aminotransferase; GGT = Gamma-glutamyltransferase; 
BUN = blood urea nitrogen; CBC = complete blood count; RBC = red blood cell; 
WBCs = white blood cells. CRP= C-reactive protein; GFR =  Glomerular 
filtration rate 
6.2.4. Pharmacokinetics (PK) and Specialty Labs 
Additional samples will be collected to evaluate PK and HAHA, HAHA-NA, tryptase in 
accordance with the SOAs in Appendix 1 and 16TAppendix 216T. The central laboratory will manage 
the storage of these samples while analysis will be performed at a specialty lab(s). 
6.2.4.1. 
Pharmacokinetics 
An optional PK assessment will be performed in consenting subjects at timepoints specified in 
the Schedule of Assessments. For subjects that reconsent to this protocol, PK assessments will 
continue to be optional except in the case of immunogenic reaction (see Section 6.2.4.3 for more 
details).  Plasma samples will be collected for estimates of PK parameters using population PK 
and exposure-response analysis, if possible, according to the SOAs in Appendix 1 and 
16TAppendix 216T. A specialty laboratory will measure plasma pamrevlumab levels using a validated 
assay.  For the population PK analysis, it is critical to accurately record the dosing time and date 
in addition to the sampling collection time and date. Both pre-dose and post-dose samples are 
required for PK as specified in Appendix 2.  Pre-dose should be within 2 hours prior to the 
administration of study treatment and post-dose should be between 1-4 hours after administration 
of study treatment has ended.   


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6.2.4.2. 
Human Anti-Human Antibodies (HAHA) and Neutralizing Human Anti-Human 
Antibodies (HAHA-NA) 
Plasma samples will be collected for evaluation of human anti-human antibodies (HAHA), 
specific to the impact of neutralizing anti-human antibodies (HAHA-NA) and the impact on 
immunogenicity, in all subjects according to the SOAs in Appendix 1 and 16TAppendix 216T.  A 
specialty laboratory will measure HAHA and HAHA-NA titers using validated assays.   
Samples/subjects with positive/specific HAHA results will be subject to evaluation of 
neutralizing antibody (HAHA-NA) assays and analyses. The prevalence and duration of binding 
and neutralizing antibodies and the effect of these antibodies on the pharmacokinetics, 
pharmacodynamics markers, efficacy, and safety of pamrevlumab will be assessed. 
6.2.4.3. 
Immunogenic Reactions 
Any immunogenic reactions, including drug-related hypersensitivity or anaphylaxis, should 
have PK, HAHA, HAHA-NA drawn within 24 hours of reaction. (A window of “within 24 
hours of reaction” could be at any point following the reaction such as 30 minutes post-reaction 
but not to exceed 24 hours following reaction).  The Tryptase sample should be drawn within 1 
to 6 hours of immunogenic reaction, but all samples should at least be collected within 24 hours 
after the anaphylactic episode.   For study visits in which PK, HAHA, and HAHA-NA were 
drawn as part of the Schedule of Assessments, if an Immunogenic reaction occurs, additional 
samples still need to be taken within 24 hours of the immunogenic reaction.  This will not be 
considered optional for the subject unless there is local consideration for total blood volume 
collection on the same day as a standard blood draw timepoint, which could preclude the 
subject from having this collection take place within 24 hours.  See Appendix 2 for more detail.   
NOTE: Patients that have an immunogenic reaction that occurs on the same date as a routine 
study blood draw and weigh less than 30kg, must wait 24 hours prior to drawing the 
corresponding PK, HAHA, HAHA-NA, and tryptase for immunogenicity per general guidance 
on the lower limit total blood volume. However, local guidance and regulations should be 
consulted regarding total blood volume to be drawn within a certain time frame and takes 
precedence over any general recommendations. 
6.2.5. Local Pulmonary Function Test (PFT)  
A pulmonary function test including FVC, FEV1, and ppPEF, will be collected locally at 
screening, Day 0, Week 12, Week 22, Week 32, Week 42, and Week 52/EOT. If the test cannot 
be performed or produces ‘Unacceptable’ grade results, the PFTs should be repeated during a 
follow-up visit, or, if an additional visit is not possible the test should be performed at the next 
scheduled on-site visit.  Valid PFT result must be obtained during the Screening Period (within 
28days of signing ICF) prior to randomization. Equipment will not be provided by the Sponsor.  
PFTs should be completed by trained staff.   
The inclusion criteria requires that the average percent predicted FVC be above 45%.  
6.2.6. NorthStar Ambulatory Assessment (NSAA) 
45TThe NorthStar Ambulatory Assessment has been developed by the Physiotherapy Assessment 
and Evaluation Group of the NorthStar Clinical Network. The NorthStar Project is supported by 
Muscular Dystrophy Campaign. The NorthStar Ambulatory Assessment (NSAA) is a 17-item 
rating scale that is used to measure functional motor abilities in ambulant children with DMD.  It 


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is usually used to monitor the progression of the45T disease and treatment effects.  Changes from 
baseline to Week 52 will be measured to assess the primary endpoint.   
• Equipment required include a size-appropriate chair or height adjustable plinth, box 
step, approximately 15 cm high, a mat, a stopwatch, a clear, straight, and marked 10 
meters pathway 
• The test must be completed without the use of any thoracic brace or leg orthoses. 
Therapist should ask the subject to complete activities listed in the table below.  
• The activities are graded as follows:  
− 2 - "Normal" - no obvious modification of activity  
− 1 - Modified method but achieves goal independent of physical assistance from 
another 
− 0 - Unable to achieve independently  
− This scale is ordinal with 34 as the maximum score indicating fully-independent 
function. 
6.2.7. Other Functional Testing 
Subjects will undergo other functional tests including the 6MWD test for eligibility, the 4-stair 
climb velocity, the 10m walk/run, the time to stand test to evaluate changes from baseline for 
secondary endpoints.  If the test is performed as part of the NSAA assessment, it does not need to 
be repeated.  Appropriate trained and experienced personnel should complete all MFTs. The 
same evaluator should evaluate the subject at each visit for consistency. All evaluators must be 
trained and pass proficiency prior to any testing. Video quality control (QC) of the muscle 
function tests (MFT)will be completed by an external vendor at Screening, Day 0, at Week 52, 
and additional visits as needed, be evaluated by an independent reviewer to confirm that the 
evaluator is consistently administering the MFT. Data will be reviewed by independent 
reviewers on an ongoing basis.  
 Loss of Ambulation (LoA) can be assessed by the Principal Investigator, Sub-Investigators or 
Clinical Evaluator (CE), and is defined as an inability to walk without any assisted devices like 
braces, and/or wheelchairs.  Principal Investigator confirms the LoA assessments by signing the 
LoA eCRFs in EDC. 
6.2.8. Exploratory Analysis 
6.2.8.1. 
Magnetic Resonance Imaging (MRI) 
MRI (Vastus lateralis muscle) assessments will be performed to evaluate fibrosis and to 
determine any changes in fibrosis score of the lower extremities vastus lateralis muscle fibrosis 
score, from baseline to Week 52. 
• A centralized image interpretation process will provide verifiable and uniform reader 
training as well as ongoing management of reader performance. This will ensure 
quality control of the images and their interpretation and decrease variability in image 
interpretations, leading to a more precise estimate of treatment effect.   


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• An Independent blinded Centralized Imaging Charter will be formed to interpret the 
MRIs.  Standardization is important for the clinically used MRI measures of vastus 
lateralis muscle fibrosis and is essential for the imaging secondary endpoint, to reduce 
variability and to ensure interpretability of the results. The charter will be formed 
according to the FDA Guidance for Industry: “Clinical Trial Imaging Endpoint 
Process Standards”. 
6.2.8.2. 
Duchenne Video Assessment  
The Duchenne Video Assessment (DVA) tool provides a standardized way to document and 
assess patient quality of movement. Caregivers will follow a standardized script to video record 
subjects doing specific movement tasks remotely using a secure mobile application within 2 
weeks prior to the clinic visits specified in the Schedule of Assessments.   
Trained physical therapists will score the videos in a secure scoring dashboard using scorecards 
with pre-specified compensatory movement criteria.  The vendor that developed the DVA, will 
manage DVA data collection, quality, and scoring. 
Caregivers will register for the study mobile application, and they will download the mobile 
application on an Apple (IOS 10+) or Android (5.1+) smartphone.  They will be provided with 
an eligible smartphone if they do not have access to one.  Caregivers will be provided with 
training materials in the study mobile application and in the study materials provided to each 
subject to learn how to video record the assigned movement activities.  The training materials 
will describe how to standardize the lighting, clothing, and set-up during the video recording and 
how to submit videos securely to study staff using the study mobile application.  Caregivers will 
provide an electronic signature within the study mobile application to document training 
completion. 
The specific movement activities are detailed in the Caregiver Manual.  Caregivers will be 
provided with study supplies.   
In addition to assigned movement tasks, all subjects will complete one caregiver choice activity 
and new ability videos (if applicable).  The caregiver choice activity is an activity that the caregiver 
will select prior to Baseline data capture and is an activity they are currently watching when they 
want to see whether the patient is getting stronger, weaker, or staying stable.  The caregiver will 
video record the same caregiver choice activity throughout the study. If caregivers observe the 
subject gaining a new ability during the study, they can video record the new ability at any time 
during the study in the study mobile application. 
The DVA vendor study staff will monitor data collection to ensure that each video meets quality 
standards.  If videos need to be re-recorded, caregivers will be contacted about re-recording the 
video.   
NOTE: Belgium and China Only:  Duchenne Video Assessments will be not be conducted.  The 
DVA vendor services and their mobile application should not be used.  There is no alternative 
for the DVA.  All references to DVA or the DVA vendor in the study protocol are not applicable 
for Belgium and China. 
 


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7. 
ASSESSMENT OF SAFETY 
7.1. 
Background 
Adverse event (AE) reports the critical building blocks to the development of the safety profile 
of the IP. Subjects should be asked non-leading questions in general terms to determine the 
occurrence of AEs, according to the schedule outlined in 16TAppendix 16T. In addition, all AEs 
reported spontaneously during the course of the study will be recorded. The investigator is 
responsible for ensuring that any AEs observed by the investigator or reported by the subject as 
defined in the study protocol are recorded in the subject’s medical record and in EDC. The 
investigator must immediately (within 24 hours of awareness) report to the sponsor or designated 
safety management vendor all serious adverse events (SAEs), regardless of whether the 
investigator believes they are related to the study drug. 
7.2. 
Definitions 
7.2.1. Definition of an Adverse Event (AE) 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment. 
An adverse event (AE) can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of a medicinal product, whether or not considered related to the medicinal product. 
The definition of adverse events includes worsening of a pre-existing medical condition. 
Worsening indicates that the pre-existing medical condition (e.g., diabetes, migraine headaches 
and gout) has increased in severity, frequency, and/or duration, and/or has an association with a 
significantly worse outcome. A pre-existing condition that has not worsened during the study or 
involves an intervention, such as elective cosmetic surgery, or a medical procedure while on 
study, is not considered an adverse event. 
7.2.2. Definition of a Serious Adverse Event (SAE) 
A serious adverse event is any adverse event or suspected adverse reaction that results in any of 
the following outcomes: 
• Death, 
• 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 


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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. 
7.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events 
7.3.1. Adverse Event Reporting Period 
The safety reporting period begins after the subject has signed the informed consent and ends 60 
days (+3 days) after the last dose of IP.  It is only required that SAEs that occur after signing 
consent but before first dose be reported prior, while all AEs and SAEs  must be reported 
thereafter.  The investigator should notify the Sponsor of any death or other SAEs occurring after 
a subject has discontinued or terminated study participation that may reasonably be related to this 
study (Section 7.3.5). Pregnancy reporting requirements are outlined in Section 7.3.6. 
Adverse events will be followed until resolved, stable, or until the subject’s last study visit or 
subject is lost to follow-up. 
7.3.2. Adverse Event Eliciting/Reporting 
During the AE reporting period, study site personnel will actively seek information from each 
subject at each visit to document any AEs occurring since the previous visit. All AEs will be 
documented in response to a general question about the subject’s well-being and any possible 
changes from the baseline 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. 
If a potential AE is reported or observed during review of a Duchenne Video Assessment video 
after the first infusion of pamrevlumab or placebo, DVA vendor study staff will report the 
potential AE to the site. 
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” 
7.3.3. Assessing Adverse Event Severity 
AEs, including abnormal clinical laboratory values, should be graded using the most current 
National Cancer Institute (NCI) Common Terminology Criteria for AE (CTCAE v. 5.0) 
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. 
7.3.4. Assessing the Adverse Event’s Relationship to IP 
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 


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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 
7.3.5. Reporting Serious Adverse Events (SAEs) 
The investigator is responsible for ensuring that all SAEs observed by the investigator or 
reported by the subject that occur after signing of the informed consent/assent through 60 days 
(+3 days) after the last dose of pamrevlumab are recorded in the subject’s medical record and are 
submitted to the Sponsor. All SAEs must be submitted to the Sponsor 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 the Sponsor. The Sponsor will report SAEs  
and/or suspected unexpected serious adverse reactions (SUSARs) as required to regulatory 
authorities, investigators/institutions, and central IRBs/IECs in compliance with all reporting 
requirements according to local regulations and Good Clinical Practice (GCP). 
There is no requirement to monitor study subjects for SAEs following the protocol-required 
reporting period or after end of study. However, these serious adverse events can be reported to 
the Sponsor. In some countries (e.g. European Union [EU] member states), investigators are 
required to report SAEs that they become aware of after the completion of the study. If SAEs are 
reported, the investigator is to report them to the Sponsor within 24 hours following the 
investigator’s knowledge of the event. SAEs reported outside of the protocol-required reporting 
period will be captured within the safety database as clinical trial cases for the purposes of 
expedited reporting; these cases will not be included in the clinical study report. 


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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 EDC. The 
following minimum information is required: 
• Subject number, sex and age 
• The date of report 
• A description of the SAE (event, seriousness of the event) 
• Causal relationship to the study drug 
Follow-up information for the event should be sent promptly. 
For each SAE observed, the investigator should obtain all of the information available about the 
event, including (but not limited to): hospital discharge diagnoses, hospital discharge note, death 
certificate, appropriate laboratory findings (including autopsies and biopsy results), and clinical 
examinations (including radiological examinations and clinical consultations). 
7.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review Board / 
Independent Ethics Committee 
The investigator is responsible for notifying his/her Institutional Review Board (IRB) or Ethics 
Committee (EC) of SAEs in accordance with local regulations. The Sponsor, or its designated 
safety vendor, will provide a copy of expedited safety reports to the investigator that it intends to 
submit to global regulatory authorities. 
7.3.5.2. 
Deaths 
The investigator will report the fatal event to the Sponsor’s medical monitor. The investigator 
must provide a causal assessment of the relationship of the event to the study drug.  
If the death occurred within the AE collection and reporting period (signed ICF to 60 days (+3 
days) after last dose) and meets the reporting criteria, the investigator must submit the SAE 
Report Form. If the investigator becomes aware of a death occurring after the AE reporting 
period and considers it related to pamrevlumab, it will be reported as an SAE.  
7.3.6. Pregnancies: Reporting and Follow-up of Female Partners of Subjects  
The outcome of all pregnancies for female partners of male subjects should be followed up and 
documented as described. If 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.  
Pregnancy itself is not an AE unless there is a suspicion that the IP 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.  


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7.3.7. Abnormal Laboratory Findings 
An abnormal laboratory finding in absence of any other signs or symptoms is not necessarily an 
AE. The investigator must review and assess all results provided by the central laboratory 
throughout the study in a timely manner, and determine whether any abnormal laboratory values 
are clinically significant (CS) or not clinically significant (NCS), and whether there are 
associated signs and symptoms. Laboratory abnormalities should be considered clinically 
significant when they occur after taking study medication, reflect a meaningful change from the 
screening value(s), and require active management (e.g., abnormalities that require study 
treatment dose modification, discontinuation, more frequent follow-up assessments, etc.).  
Clinically significant laboratory abnormalities will be reported as AEs. If the abnormal 
laboratory finding is accompanied by signs or symptoms, report the signs and symptoms as the 
AE in lieu of the abnormal laboratory value. If a diagnosis is available, report the diagnosis. 
 
7.3.8. Hypersensitivity/Anaphylactic Reactions: 
Hypersensitivity and anaphylactic reactions will be monitored throughout the study, using the 
criteria below as defined per Sampson et al. 2006 (45TSampson, 200645T). 
Anaphylaxis is highly likely when the following criteria is fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-
uvula). 
And at least one of the following criteria: 
a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that 
patient (minutes to several hours):  
 a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen 
lips-tongue-uvula)  
 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.  
7.3.9. Safety Monitoring  
Safety will be assessed throughout the study. A medically complete baseline profile of each 
subject will be established through medical history, a complete physical examination including 
vital signs and laboratory tests.  During the course of the study, vital signs and laboratory tests 


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will be performed at frequent intervals as described in 16TAppendix 16T and 16TAppendix 216T. 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 the Sponsor. 
7.3.9.1. 
Special Reporting Situations 
Special Reporting Situations for the IP; pamrevlumab (or placebo) that require safety evaluation 
include: 
• Overdose (any dose greater than 4.1g) 
• Suspected abuse/misuse 
• Inadvertent or accidental exposure 
• Medication error (e.g. incorrect dose administered) 
• Drug-drug interactions 
Report special situations to the Sponsor’s Safety department or delegate within 24 hours of the 
investigator’s knowledge of the event.  See Study Reference Manual for detailed reporting 
instructions. 
7.3.9.2. 
 Data Monitoring Committee (DMC) 
A Data Monitoring Committee (DMC) will be utilized and will be composed of external experts. 
Composition and responsibilities of the DMC will be defined in a separate DMC charter. The 
DMC responsibilities will include review of the safety data in addition to the routine Sponsor 
pharmacovigilance activities.  


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8. 
STATISTICS 
8.1. 
Sample Size Determination 
With a total sample size of 70 subjects allocated in a 1:1 ratio between the treatment arm and 
placebo, the study will achieve at least 80% power to detect an effect size of 0.705 (assuming a 
treatment difference of 6.0 points in linearized total NSAA with common standard deviation of 
8.5, or a treatment difference of 1.91 in raw total NSAA with common standard deviation of 
2.71) in the mean change from baseline in the total NSAA  score with a one-sided significance 
level (alpha) of 0.025.  
8.2. 
Analysis Populations  
The analysis population is defined through appropriate inclusion/exclusion criteria to reflect the 
targeted patient population for approval. 
8.2.1. Intent to Treat (ITT) Population 
The ITT population is defined as all randomized subjects regardless of study treatment received.  
Subjects will be analyzed according to the treatment as randomized. The primary analysis of 
efficacy will be based on the ITT population. 
8.2.2. Safety Population 
The safety population is defined as all subjects who have received the study medication.  Safety 
data will be summarized based on the Safety population. Subjects will be analyzed according to 
the treatment as received. 
8.3. 
Statistical Analysis 
8.3.1. General Considerations 
The primary efficacy endpoint will be tested at the significance level of 0.05.  Upon observing a 
significant treatment difference in the primary endpoint, the secondary endpoints will be tested 
taking into consideration the adjustment for the family-wise error-rate of 0.05. The fixed 
sequence testing procedure will be used for testing of the secondary endpoints in the order listed 
in section 3.2.2.   
Efficacy and safety analyses for treatment comparisons will be based on data observed during the 
main study.  Data from the OLE period will be summarized descriptively.  
Treatment comparison will be based on data collected during double-blind placebo-controlled 
main study period.  Descriptive summary will be provided for data during the open label 
extension. 
Baseline characteristics, safety, efficacy and other data will be summarized by treatment arm 
based on available data in the ITT/Safety Population, except for the parameters specifically 
indicated otherwise.  
Descriptive statistics for continuous variables include: n, mean, standard deviation or standard 
error, median, minimum, and maximum. Categorical variables will be presented by frequency 
counts of subjects and percentage. Two-sided 95% confidence intervals will be included for the 
key efficacy parameters. 


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8.3.2. Subject Enrollment and Disposition 
The number (%) of subjects who completed or discontinued the study and reasons for early 
discontinuation will be summarized by treatment for subjects in the ITT population. 
8.3.3. Demographics and Baseline Characteristics 
Demographics and baseline characteristics will be summarized for subjects in the ITT 
population. 
8.3.4. Efficacy Analyses 
8.3.4.1. 
Analysis of Primary Endpoint Change in Total NSAA Score from Baseline to 
Week 52 
The primary endpoint, change in the total NSAA Score, from baseline to Week 52 will be 
analyzed using a Mixed Model for Repeated Measure (MMRM) with treatment, visit visit-by-
treatment interaction, randomization stratification, and baseline total score of NSAA, with an 
unstructured covariance matrix for the within subject covariance over time. The primary analysis 
will be based on observed data from subjects in the ITT population.   
The analysis will take into account the potential intercurrent events as follows: 
• Treatment discontinuation (such as: due to AEs, Lost to Follow-Up, Withdrawal by 
Subject, Physician Decision, Protocol Deviations, etc.): Treatment policy strategy: 
use all observed data, and missing data will be implicitly imputed under missing at 
random assumption. 
• Death: Worst observation prior to death is imputed to Week 52 
 
As sensitivity analysis, the analysis of covariance model (ANCOVA) model after multiple 
imputations (ANCOVA –MI) will be also applied. The model will include treatment, with 
randomization stratification and baseline total  score of NSAA as covariates.  
There will be 2 sets of multiple imputations performed for the missing data based on the two 
missing data pattern assumptions separately. One assumption of the missing data pattern is 
missing at random (MAR). Under the MAR assumption, the missing data after loss to follow-up 
will be imputed as continuing the trend of previously observed data, and this will be done 
separately for each treatment. The other missing pattern is missing not at random (MNAR).  
Under the MNAR assumption, the missing data after loss to follow-up for the pamrevlumab 
subjects will be imputed as having the same data distribution as those in the placebo group, and 
the missing data of the placebo subjects will be imputed as continuing the trend of previously 
observed data. 
After a multiple imputation, the primary endpoint of change from baseline to week 52 total  
score of NSAA value will be calculated from the observed and imputed data and will be 
analyzed using analysis of covariance model (ANCOVA).  The ANCOVA model will include 
the same covariates as in the primary analysis.   
 


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8.3.4.2. 
Analyses of Secondary Endpoints 
The following analyses will take into account the potential intercurrent events as follows: 
• Treatment discontinuation (such as: due to AEs, Lost to Follow-Up, Withdrawal by 
Subject, Physician Decision, Protocol Deviations, etc.): Treatment policy for missing 
data will be implicitly imputed by the model under missing at random assumption. 
• Death: Worst observation prior to death is imputed to Week 52. 
8.3.4.2.1. Changes in 4-stair climb Velocity (4SCV) assessment from baseline to Week 52 
The change from baseline to week 52 in 4-stair climb velocity (4SCV) assessment will be 
analyzed, using a Mixed Model for Repeated Measure (MMRM) with treatment, visit, visit-by-
treatment interaction, randomization stratification, and baseline 4-stair climb velocity (4SCV) 
assessment with an unstructured covariance matrix for the within subject covariance over time.   
8.3.4.2.2. Changes in 10M Walk/Run assessment from baseline to Week 52 
The change from baseline to week 52 in 10-meter walk/run test will be analyzed, using a Mixed 
Model for Repeated Measure (MMRM) with treatment, visit, visit-by-treatment interaction, 
randomization stratification, and baseline 10-meter walk/run test with an unstructured covariance 
matrix for the within subject covariance over time.  
8.3.4.2.3. Changes in Time to Stand (TTSTAND) assessment from baseline to Week 52 
The change from baseline to week 52 in time to stand (TTSTAND) will be analyzed, using a 
Mixed Model for Repeated Measure (MMRM) with treatment, visit, visit-by-treatment 
interaction, randomization stratification, and baseline time to stand (TTSTAND) with an 
unstructured covariance matrix for the within subject covariance over time.  
8.3.4.2.4. Time to Loss of ambulation (LoA), from baseline to Week 52 
Time to loss of ambulation (LoA) will be summarized using the Kaplan-Meier method. The Cox 
proportional hazard model including treatment and randomization stratification factor will be 
used to compare the 2 treatment arms and to estimate the hazard ratio and the corresponding 95% 
confidence interval.   
8.3.4.2.5. Exploratory Analyses  
8.3.4.2.5.1. Change in fibrosis score of the lower extremities Vastus Lateralis muscle from 
baseline to Week 52, assessed by MRI 
The change from baseline at week 52 in fibrosis score of the vastus lateralis muscle will be 
analyzed using a Mixed Model for Repeated Measure (MMRM) with treatment, visit, visit-by-
treatment interaction, and baseline score as fixed effects, with an unstructured covariance matrix 
for the within subject covariance over time.   
Exploratory endpoints, the change from baseline at week 52 in fibrosis score of lower extremities 
muscle will be analyzed using the same intercurrent handling and analysis method as for the 
primary endpoint. 


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8.3.4.2.5.2. Changes in ppFVC and ppPEF from Baseline to Week 52 
The Change from baseline to Week 52 in ppFVC will be analyzed using a Mixed Model for 
Repeated Measure (MMRM) with treatment, visit, visit-by-treatment interaction, and baseline 
ppFVC as fixed effects, with an unstructured covariance matrix for the within subject covariance 
over time.   
The Change from baseline to Week 52 in ppPEF will be analyzed using a Mixed Model for 
Repeated Measure (MMRM) with treatment, visit, visit-by-treatment interaction, and baseline 
ppPEF as fixed effects, with an unstructured covariance matrix for the within subject covariance 
over time. 
Exploratory endpoints, the change from baseline to Week 52 in ppFVC and ppPEF will be 
analyzed using the same intercurrent handling and analysis method as for the primary endpoint. 
8.3.5. Pharmacokinetic Analyses 
A population PK analysis will be defined in a separate plan. 
8.3.6. Safety Analyses   
All treatment-emergent adverse events (TEAEs) will be summarized by treatment arm, 
including: TEAEs Grade ≥3, treatment-emergent serious adverse events (TESAEs), deaths, and 
TEAEs leading to study or investigational product discontinuation.  
Clinically significant changes from baseline in vital signs and laboratory tests will be 
summarized.  Hypersensitivity/anaphylactic reactions will be monitored. 
Additionally, the following safety analyses will be conducted: 
• Number and percentage subjects with bone fractures. 
• Annualized height velocity, HV (cm/year) from Baseline to Week 52 
8.4. 
Statistical Analysis Plan 
The Statistical Analysis Plan (SAP) will include detailed analysis methods, statistical models, 
definitions, missing data handling as well as other data handling rules. It will document 
additional exploratory endpoints that are not specified in the protocol.  The SAP will be finalized 
prior to database lock and treatment unblinding.  
 
 
 


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


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10. 
ETHICS 
10.1. 
Ethical Considerations 
The study will be conducted in accordance with applicable regulatory requirements, the 
International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice 
(GCP), the Declaration of Helsinki, any other applicable regulatory requirements, and 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) requirements. 
10.2. 
Communication with the Institutional Review Board or Independent Ethics 
Committee 
This protocol, the Informed Consent Form, the 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 reapproval by the IRB/IEC annually or as required 
by the policies and procedures established by the IRB/IEC. Copies of the investigator’s annual 
report and other required reports submitted to the IRB/IEC and copies of the IRB/IEC 
continuance of approval must be furnished to FibroGen or designee. A copy of the signed FDA 
Form 1572 or other qualified investigator statement (as required) must also accompany the above 
approval letter provided to FibroGen. 
Investigators are also responsible for promptly informing the IRB/IEC of any protocol changes 
or amendments, changes to the 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 their legally acceptable representative) 
an IRB/IEC-approved written Informed Consent Form (ICF) in their native language.  The 
approved written informed consent must adhere to all applicable laws in regards to the safety and 
confidentiality of the subjects.  To obtain and document informed consent, the investigator 
should comply with applicable regulations, and adhere to ICH GCP standards and the ethical 
principles in the Declaration of Helsinki (October 2008). 
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 


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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. 
Guidance for Clinical Teams: For studies conducted in the United States, each subject must 
provide his or her consent for the use and disclosure of personal health information under the 
U.S. Health Insurance Portability and Accountability Act (HIPAA) regulations by signing a 
HIPAA Authorization Form. The HIPAA Authorization Form may be part of the ICF or may be 
a separate document. IRB review may or may not be required for the HIPAA Authorization 
Form according to study site policies. 
10.4. 
Subject Confidentiality 
The confidentiality of records that could identify subjects should be protected, respecting the 
privacy and confidentiality rules in accordance with applicable regulatory requirements.  
Subject medical information obtained as part of this study is confidential and may only be 
disclosed to third parties as permitted by the Informed Consent and HIPAA Authorization Form 
or separate authorization to use and disclose personal health information signed by the subject, or 
unless permitted or required by law. The subject may request in writing that medical information 
be given to his/her personal physician. 
The processing of personal data in pursuit of this study will be limited to those data that are 
reasonably necessary to investigate the utility of the study medications used in this study.  These 
data will be processed with adequate precautions to ensure confidentiality according to local 
laws.  
FibroGen ensures that the personal data are:  
• collected for a specified and legitimate purpose 
• processed fairly and lawfully 
• accurate and up to date 
Explicit consent for the processing of personal data will be obtained prospectively from the 
participating subject.  FibroGen and/or designees whose responsibilities require access to 
personal data agree to keep the identity of study subjects confidential.  This confidentiality will 
be maintained throughout the complete data processing. 
Study subjects will be entitled to request confirmation of the existence of personal data held by 
FibroGen and will have the right to rectify erroneous or inaccurate data prior to database lock. 


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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 their study-related records, including 
personal information and medical records. 
11.3. 
Data Collection, Handling, and Verification 
All required data will either be entered into EDC by authorized site personnel or will be provided 
as a data transfer from authorized service providers (such as laboratory results from a central 
laboratory, or central imaging vendor). Data will be entered or uploaded into a validated, clinical 
database compliant with 21 CFR Part 11 regulations.  
All subject data will be reviewed by Sponsor and/or designee. Data that appear inconsistent, 
incomplete or inaccurate will be queried for site clarification. 
Medical history, adverse events and medications will be coded using industry standard 
dictionaries (e.g., MedDRA and World Health Organization Drug [WHODrug]) Dictionary. 
The investigator is responsible for reviewing, verifying, and approving all subject data (i.e. CRFs 
and queries) throughout the duration of the study and prior to study completion, ensuring that all 
data are verifiable with source documents. 
DVA video data will be recorded by the caregiver in a secure, authenticated study mobile 
application and transmitted, using a secure Web service, to the mobile application database and 
encrypted.  All media files received on the platform will be stored in an encrypted format.  Data 
will be stored via secure data interchange and hosted on a secure Microsoft Azure server.  
Trained physical therapists will score the raw video data in a secure scoring dashboard, and de-
identified scoring and video data will be transferred electronically to the sponsor or designee at 
predefined intervals during the study. 
MFT video data will be recorded by the site user on a restricted pre-configured managed iPad, 
video data is then uploaded directly via HTTPS & TLS 1.2 to a secure web-based application 
and database which is encrypted using ASE256bit encryption. All data uploaded to the platform 
will be stored in an encrypted format. Data will be stored by a secure data interchange and hosted 
on a secure Amazon Web Services cloud servers within the European Union. Trained physical 
therapists will score the raw video data and de-identified scoring for accuracy of clinical 
evaluator performance. Video data will be uploaded to the secure web based application. Quality 


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reports will be available to the sponsor by access to a quality controlled report library.  The 
Sponsor will have no access to de-identified videos and will not be transferred to the sponsor at 
any time. 
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, the Sponsor, and to the regulatory authorities, if required. 
11.5. 
Retention of Data 
A Sponsor 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, the 
Sponsoror designee, the investigator agrees to keep records, including the identity of all 
participating subjects (e.g. 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 the Sponsor 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.  
AnyiInvestigator(s) added as investigational staff to the form FDA 1572 or equivalent 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 
Annexstad EJ, Lund-Petersen I, Rasmussen M. (2014) Duchenne muscular dystrophy. Tidsskr 
Nor Laegeforen. 134(14):1361-1364. 
Au CG, Butler TL, Sherwood MC, et al. (2011) Increased connective tissue growth factor 
associated with cardiac fibrosis in the mdx mouse model of dystrophic cardiomyopathy. Int J 
Exp Pathol 92: (1):57-65 
Birnkrant DJ, Bushby K, Bann CM, et al. (2018) Diagnosis and management of Duchenne 
muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. The 
Lancet Neurology 17:347-361. 
Bornstein P, Sage E (2002) Matricellular proteins: extracellular modulators of cell function. Curr 
Opin Cell Biol 14: (5):608 
Bushby K, Finkel R, Birnkrant DJ, et al. (2010) Diagnosis and management of Duchenne 
muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. 
Lancet Neurol 9: (1):77-93 
Bushby K, Muntoni F, Bourke JP. (2003) 107th ENMC international workshop: the management 
of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th-9th June 2002, 
Naarden, the Netherlands. Neuromuscul Disord. 13(2):166-172. 
Buyse GM, Voit T, Schara U, Straathof CSM, D'Angelo MG, Bernert G, Cuisset JM, Finkel RS, 
Goemans N, McDonald CM, Rummey C, Meier T; DELOS Study Group. Efficacy of idebenone 
on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids 
(DELOS): a double-blind randomised placebo-controlled phase 3 trial. Lancet. 2015 May 
2;385(9979):1748-1757. doi: 10.1016/S0140-6736(15)60025-3. Epub 2015 Apr 20. PMID: 
25907158. 
Chen CC, Lau LF (2009) Functions and mechanisms of action of CCN matricellular proteins. Int 
J Biochem Cell Biol 41: (4):771-783 
Connolly AM, Malkus EC, Mendell JR, et al. (2015) Outcome reliability in non-ambulatory 
boys/men with Duchenne muscular dystrophy.  Muscle Nerve. 51(4):522-532. 
Desguerre I, Mayer M, Leturcq F, et al. (2009) Endomysial fibrosis in Duchenne muscular 
dystrophy: a marker of poor outcome associated with macrophage alternative activation. J 
Neuropathol Exp Neurol 68: (7):762-773 
Emery AE (1991) Population frequencies of inherited neuromuscular diseases--a world survey. 
Neuromuscul Disord 1: (1):19-29 
Epstein AE, DiMarco JP, Ellenbogen KA, et al. (2008) ACC/AHA/HRS 2008 Guidelines for 
Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of 
Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 
51(21):e1-62. 
Falzarano MS, Scotton C, Passarelli C, et al. (2015) Duchenne muscular dystrophy: from 
diagnosis to therapy. Molecules. 20(10):18168-18184. 
Finder J, Mayer OH, Sheehan D, et al. (2017) Pulmonary endpoints in Duchenne muscular 
dystrophy. A workshop summary. Am J Respir Crit Care Med. 196(4):512-519. 


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Kharraz Y, Guerra J, Pessina P, et al. (2014) Understanding the process of fibrosis in Duchenne 
muscular dystrophy. Biomed Res Int 2014:965631 
Leung DG, Germain-Lee EL, Denger BE, et al. (2011)  Report on the second endocrine aspects 
of Duchenne muscular dystrophy conference December 1-2, 2010, Baltimore, Maryland, USA. 
Neuromuscul Disord. 21(8):594-601. 
Magrath P, Maforo N, Renella P, et al. (2018) Cardiac MRI biomarkers for Duchenne muscular 
dystrophy.  Biomark Med. 12(11):1271-1289 
Mayer OH, Finkel RS, Rummey C, et al. (2015) Characterization of pulmonary function in 
Duchenne muscular dystrophy. Pediatr Pulmonol. 50(5):487-494 
McDonald CM, Henricson EK, Abresch RT, et al. (2018) Long-term effects of glucocorticoids 
on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a 
prospective cohort study. Lancet. 391(10119):451-461 
McKim DA, Katz SL, Barrowman N, et al. (2012) Lung volume recruitment slows pulmonary 
function decline in Duchenne muscular dystrophy. Archives of Physical Medicine and 
Rehabilitation 93: (7):1117-1122 
Meier T, Rummey C, Leinonen M, et al. (2017) Characterization of pulmonary function in 10-18 
year old patients with Duchenne muscular dystrophy. Neuromuscul Disord. 27(4):307-314 
Morales MG, Cabello-Verrugio C, Santander C, et al. (2011) CTGF/CCN-2 over-expression can 
directly induce features of skeletal muscle dystrophy. J Pathol 225: (4):490-501 
Morales MG, Gutierrez J, Cabello-Verrugio C, et al. (2013) Reducing CTGF/CCN2 slows down 
mdx muscle dystrophy and improves cell therapy. Hum Mol Genet 22: (24):4938-4951 
Pane M, Messina S, Bruno C, et al. (2013) Duchenne muscular dystrophy and epilepsy. 
Neuromuscul Disord. 23(4):313-315. 
Perbal B. (2004) CCN proteins: multifunctional signalling regulators. Lancet 363: (9402):62-64 
Phillips MF, Quinlivan RC, Edwards RH, et al. (2001) Changes in spirometry over time as a 
prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med 
164: (12):2191-2194 
Porter JD, Merriam AP, Leahy P, et al. (2003) Dissection of temporal gene expression signatures 
of affected and spared muscle groups in dystrophin-deficient (mdx) mice. Hum Mol Genet 
12:1813-21. 
Rachfal AW, Brigstock DR (2005) Structural and Functional Properties of CCN Proteins. Vitam 
Horm 70:69-103 
Ricotti V, Selby V, Ridout D, et al. (2019) Respiratory and upper limb function as outcome 
measures in ambulant and non-ambulant subjects with Duchenne muscular dystrophy: A 
prospective multicentre study. Neuromuscul Disord. 29(4):261-268 
Sampson HA, Muñoz-Furlong A, Campbell RL, et al. (2006) Second symposium on the 
definition and management of anaphylaxis: summary report--Second National Institute of 
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy 
Clin Immunol. 117(2):391-397. 


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Schram G, Fournier A, Leduc H, et al. (2013) All-cause mortality and cardiovascular outcomes 
with prophylactic steroid therapy in Duchenne muscular dystrophy. J Am Coll Cardiol 61: 
(9):948-954 
Schwartz GJ, Schneider MF, Maier PS, et al. Improved equations estimating GFR in children 
with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney 
Int. 2012;82(4):445-453. 
Seferian AM, Moraux A, Annoussamy M, et al. (2015) Upper limb strength and function 
changes during a one-year follow-up in non-ambulant patients with Duchenne Muscular 
Dystrophy: an observational multicenter trial. PLoS One. 10(2):e0113999. 
Sun G, Haginoya K, Wu Y, et al. (2008) Connective tissue growth factor is overexpressed in 
muscles of human muscular dystrophy. J Neurol Sci 267: (1-2):48-56 
Szigyarto CA, Spitali P. (2018) Biomarkers of Duchenne muscular dystrophy: current findings. 
Degener Neurol Neuromuscul Dis. 8:1-13 
Tandon A, Villa CR, Hor KN, et al. (2015) Myocardial fibrosis burden predicts left ventricular 
ejection fraction and is associated with age and steroid treatment duration in duchenne muscular 
dystrophy. J Am Heart Assoc 4: (4):e001338 
Tangsrud SE, Carlsen KC, Lund-Petersen I, et al. (2001) Lung function measurements in young 
children with spinal muscle atrophy; a cross sectional survey on the effect of position and 
bracing. Arch Dis Child 84: (6):521-524 
Tsuda T (2018) Clinical manifestations and overall management strategies for Duchenne 
muscular dystrophy. Methods Mol Biol. 1687:19-28 
van Westering TL, Betts CA, Wood MJ. (2015) Current understanding of molecular pathology 
and treatment of cardiomyopathy in duchenne muscular dystrophy. Molecules. 20(5):8823-8855 
Vial C, Zúñiga LM, Cabello-Verrugio C, et al. (2008) Skeletal muscle cells express the 
profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their 
dedifferentiation. J Cell Physiol. 215(2):410-421. 
Walter MC, Reilich P. (2017) Recent developments in Duchenne muscular dystrophy: facts and 
numbers. J Cachexia Sarcopenia Muscle 8:681-685 
Wu B, Cloer C, Lu P, et al. (2014) Exon skipping restores dystrophin expression, but fails to 
prevent disease progression in later stage dystrophic dko mice. Gene Ther. 21(9):785-793 
Yiu EM, Kornberg AJ. (2015) Duchenne muscular dystrophy. J Paediatr Child Health. 
51(8):759-764. 
Zhou L, Lu H. (2010) Targeting fibrosis in Duchenne muscular dystrophy. J Neuropathol Exp 
Neurol.69(8):771-776 
 
 


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14. 
APPENDICES 


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APPENDIX 1. 
SCHEDULE OF ASSESSMENTS 
 
  
Screening 
Treatment Period (Weeks)Pa 
  
(within 4 
Weeks of 
Day 0) 
Day 
0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52
/ 
E
O
T 
Wk 
56 
28 
days 
post 
last 
dosej 
60 
days 
(+3 
days) 
post 
dose 
(pho
ne 
call)j 
Informed 
Consent/ 
Assent 
X 
 
Eligibility  
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
Physical ExamPc 
X 
X 
X 
X 
X 
X 
 
Weight/Weight 
Based 
AdjustmentPh 
X 
X 
X 
X 
X 
 


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PFTs  (local)Pk 
X 
XPj 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
XPh 
 
Vital Signsd 
X, 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry & 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
 
6MWD Testn 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
MFTs (NSAA, 4-
Stair Climb 
Velocity, 10M 
Walk/Run, Time 
to Stand, LoA)Pe 
X 
Xj 
X 
X 
X 
X 
X 
XPb,h 
 
Muscle MRIP 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
XPh 
 
PK (Optional) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Specialty Lab: 
HAHAand 
HAHA-NA 
X 
X 
X 
X 
X 
XPh 
 
Duchenne Video 
AssessmentPf 
X 
X 
X 
XPh 
 
Pamrevlumab/ 
Placebo Infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse Events / 
SAEsm 
XPg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Concomitant 
Medications  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: SAE = serious adverse event; EOS = End of Study; ET= Early Termination; HAHA = human anti-human antibody  
a) Visit window of ± 3 days starting at Week 2 
b) At the Early Termination visit, MFTs do not need to be repeated if the last one was performed within 4 weeks.   
c) Full physical exam including chest auscultation  
d) Vital signs (pulse, respiration, sitting BP, temperature) to be collected at every visit and twice during infusions (within 30 minutes prior to (pre-
infusion), and within 30 minutes post-infusion. 
e.) MFTs (NSAA, 4-Stair Climb Velocity, 10M Walk/Run, Time to Stand and Loss of Ambulation (LoA))  
f) Duchenne Video Assessment to be performed remotely within the interval between the prior scheduled study visit and next scheduled study 
visit. 
g) Only collecting SAEs prior to dosing 
h) HAHA, HAHA-NA MRI, MFTs, PFTs, and Duchenne’s video assessment only to be completed during the early termination visit 
i) If the subject is not going into the OLE, he should complete a final safety follow-up that consists of a visit at week 56 and a final safety follow-
up phone call 60 days (+3days) after the last infusion visit. 
j) MFTs and PFTs are collected at screening and must be repeated prior to randomization and first infusion on Day 0.  They may be conducted up 
to 3 days in advance of the Day 0 visit.  The PFT results from both time points will be used to establish baseline values.  The results from MFTs at 
Day 0 will be used to establish baseline. 
k)  PFTs include FVC, FEV1, and ppPEF to be done locally per the Institution’s standards 
l)  Randomization may be performed within 2 days prior to Day 0 visit, after subject is confirmed eligible (see footnote “j”). 
m) SAEs are collected from date of consent through EOS. AEs are collected from Day 0 through EOS.  Number and percentage of bone fractures 
is captured from Day 0 through EOS.  Bone fractures should be collected in the EDC as AEs naming them using the CRF completion guidelines 
n) Two 6MWD test results are needed within 3 months prior to Day 0 to establish eligibility prior to randomization (see Section 4.1).  These tests 
may be conducted during the screening window, if historical results are not available. 
  


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APPENDIX 2. 
PHARMACOKINETIC AND PHARMACODYNAMIC SAMPLING 
Timepoint Pa 
PK 
(Plasma)
HAHAb 
and HAHA - 
NA(Plasma) 
Tryptase 
Day 0 
Xc 
Xf 
Week 2 
Xc 
Week 8 
Xc 
Week 16 
Xc 
Week 24 
Xc 
Xf 
Week 32 
Xc 
Xf 
Week 40 
Xc 
Xf 
Week 48 
Xc 
Xf 
Week 56/EOS 
or ET 
Xd 
Xf 
Immunogenic 
Reaction 
Xe 
Xe 
Xe 
Abbreviations: PK = Pharmacokinetic; HAHA = human anti-human antibody; HAHA-NA = 
human anti-human antibody neutralizing antibody EOS = End of Study; ET = Early 
Termination; 
a.) For all time points, the actual date and time of sample collection must be recorded, in addition to 
date and time of study treatment administration. 
b.) Separate samples for HAHA and HAHA-NA should be collected within 2 hours prior to the 
administration of study treatment. Samples/subjects with positive/specific HAHA results will be subject 
to evaluation of neutralizing antibody assay testing. 
c.) Both Pre (within 2 hours prior to infusion start) and Post dose (between 1- 4 hours post infusion 
completion)  
d.) Only one sample is required. 
e.)  PK, HAHA and HAHA-NA, tryptase sampling will be required following the immunogenic 
reaction. NOTE: Local guidance and regulations on the maximum allowable total blood volume should 
be followed.  Please review your lower weight patients (see section 6.2.4.3 for more details). 
f.) While samples for HAHA and HAHA-NA are drawn for all subjects, only samples/subjects with 
positive/specific HAHA results will be subject to neutralizing antibody (HAHA-NA) testing. 


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APPENDIX 3. 
NORTHSTAR AMBULATORY ASSESSMENT (NSAA) 
 
The NorthStar Assessment (NSAA) worksheet should be used to document the scores for the 
assessments.  A separate manual will be provided as a guide on how the tests should be 
conducted. Note: The Time to Stand test is called Rise from Floor and is contained within the 
NSAA. 
 
Activity 
2 
1 
0 
Score 
1. Stand 
*3 
Stands upright, still, symmetrical, 
without compensation (heels flat and 
hips in neutral rotation) for minimum 
count of 3 seconds 
Stands still but with compensation (e.g. 
on toes or with legs abducted or with 
bottom stuck out/hip flexion, etc.) for 
minimum count of 3 seconds 
Cannot stand still or cannot 
stand independently, needs 
support (even minimal) 
2. Walk 
*3 
Walks consistently with heel-toe or flat- 
footed gait pattern 
Persistent or habitual toe walker, unable 
to heel-toe consistently 
Loss of independent ambulation 
– may use knee-ankle-foot 
orthosis (KAFO) or walk short 
distances with assistance 
3. Stand up 
from chair 
*3 
Able to stand up keeping arms folded 
With help from thighs / push on chair / 
prone turn or alters starting position by 
widening base (moving feet apart) 
Unable 
4. Stand on 
one leg – 
right *3.5 
Able to stand upright in a relaxed 
manner (no fixation) for a count of 3 
seconds 
Stands but either momentarily or with 
trunk side-flexion (20◦) or needs fixation 
e.g. by thighs adducted 
Unable 
5. Stand on 
one leg – left 
*3.5 
Able to stand upright in a relaxed 
manner (no fixation) for a count of 3 
seconds 
Stands but either momentarily or with 
trunk side-flexion (20◦) or needs fixation 
e.g. by thighs adducted 
Unable 
6. Climb box 
step – right 
*3 
Faces step – no support needed 
Goes up sideways / rotates trunk / 
circumducts hip / needs hands for 
balance or hands on legs 
Unable to perform 
independently 
7. Descend 
box step – 
right *3.5 
Faces forward, steps down controlling 
weight-bearing leg. No support needed 
Sideways / skips down / needs hands for 
balance or hands on legs 
Unable without more than 
minimal support, or requires 
hands for support 
8. Climb box 
step – left *3 
Faces step – no support needed 
Goes up sideways / rotates trunk / 
circumducts hip / needs hands for 
balance or hands on legs 
Unable to perform 
independently 
9. Descend 
box step -left 
*3.5 
Faces forward, steps down controlling 
weight-bearing leg. No support needed 
Sideways / skips down / needs hands for 
balance or hands on legs 
Unable without more than 
minimal support, or requires 
hands for support 
10. Lifts head 
*4 
In supine, full neck flexion, head must be 
lifted in mid-line. Chin moves towards 
chest 
Head is lifted through side flexion, partial 
neck flexion, or with protraction 
Unable. No clearance of head 
from surface 
11. Gets to 
sitting *3 
Starts in supine – may use one hand / 
arm to push up 
Uses two arms / pulls on legs or turns 
towards floor or uses momentum/rocking 
Unable 


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12. Rise from 
floor *4 
No evidence of Gower’s manoeuvre. 
Exhibits at least one of the components 
described above – in particular rolls 
towards floor, and/or use hand(s) on legs 
(a) NEEDS to use external 
support object e.g. chair, wall 
OR (b) Unable NO TIME 
RECORDED 
13. Stands 
on heels *3.5 
Both feet at the same time, clearly 
standing on heels only (acceptable to 
move a few steps to keep balance) for 
count of 3 
Raises forefoot on both feet – all 
metatarsal heads off ground – or clearly 
dorsiflexes one foot only 
Unable 
14. Jump *3 
Both feet at the same time, clear the 
ground simultaneously and land at the 
same time 
One foot after the other (skip) or does 
not fully clear both feet at the same time 
Unable 
15. Hop right 
leg *4 
Entire foot clears the floor 
Able to bend knee AND raise heel, no 
floor clearance 
Unable or only raises heel 
16. Hop left 
leg *4 
Entire foot clears the floor 
Able to bend knee AND raise heel, no 
floor clearance 
Unable or only raises heel 
17. Walk Run 
(10 m) *3 
Both feet off the ground (no double 
stance phase during running) 
‘Duchenne jog’ or fast walk 
Walk 
TOTAL= 
/34 
 
 
 


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APPENDIX 4. 
OPEN LABEL EXTENSION (OLE) 
This is an optional open-label, single arm extension to evaluate long-term efficacy and safety of 
pamrevlumab in DMD subjects. Subjects who complete week 52 of the main study (regardless of 
the number of study drug infusions received) will be eligible to participate in the open-label, 
extension (OLE) where all subjects will be treated with pamrevlumab.  After completing Week 
52 of the main study, participants electing to go into the OLE will  move to Week 2 of the OLE.  
The EOS visit will be completed at the end of participation in the OLE. If a subject discontinues 
the main study early for any reason, they will not be eligible for inclusion in the OLE.  
 
Each subject will receive pamrevlumab (35 mg/kg) intravenously, every 2 weeks until the last 
subject from the phase 3, DMD program completes 52 weeks of treatment on OLE or when 
Pamrevlumab is commercially available or when the Sponsor decides to end the study.   
Upon completion of the trial, subjects will be asked to return to the investigative site 4 weeks 
after their last treatment visit to complete a final follow-up visit and will receive a final safety 
follow-up phone call 60 days (+3 days) after the last dose.  See parent study protocol for detailed 
information on study drug formulation, storage, and administration. All subjects will receive 
pamrevlumab in an open-label manner. Note: No unblinding of subject’s treatment assignment in 
the main study will occur for purposes of OLE participation. 
 
The following conditions are excluded for continued participation in this OLE phase: 
• Use of any investigational drugs, or participation in a clinical trial with an 
investigational new drug, other than participation in the main study. 
• History of allergic or anaphylactic reaction to human, humanized, chimeric or murine 
monoclonal antibodies, or experienced an allergic or anaphylactic reaction to study 
drug or any component of study drug. 
• Subjects who withdrew informed consent while participating in the main study, or 
who discontinued early from the main study for any reason. 
• The Investigator judges that the subject is not suitable for participation, or is unable to 
fully participate in the OLE phase and complete it for any reason, including inability 
to comply with study procedures and treatment, or any other relevant medical or 
psychiatric conditions 
 
1. Endpoints 
Ambulatory functional assessments: 
• Change in NorthStar Ambulatory Assessment (NSAA) total score.  
• Change in 4-stair climb Velocity (4SCV) assessment.  
• Change in the 10-meter walk/run test.  
• Change in Time to Stand (TTSTAND).  
• Change of the time of Loss of Ambulation (LoA) assessment  


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Safety assessments 
• Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse 
events (TESAEs), clinically significant laboratory test abnormalities, and 
discontinuation of treatment due to TEAEs serve as the safety assessments for this 
OLE. 
• Number and percentage of subjects with hospitalizations due to any serious adverse 
events with pulmonary and/or cardiac cause(s), 
• Number and percentage of subjects with bone fractures.  
• Annualized height velocity from Baseline of OLE to Week 52 of OLE 
 
2. Study Enrollment 
All subjects participating in the Open Label Extension must have completed treatment through 
the primary endpoint and completed the Week 52 visit on the parent pamrevlumab DMD study. 
The study investigator must consider the subject medically stable for continued treatment. 
Written consent/assent by the subject and/or their legal guardian (as required by the site’s 
IRB/IEC) must be obtained prior to the subject’s participation in the OLE.  Administration of 
currently approved DMD therapies is allowed during the OLE treatment period, if deemed 
acceptable by the investigator.  Administration of such therapies must be withheld for three 
hours after the end of pamrevlumab infusion. 
 
3. Study Visits and Assessments 
All study visits will be performed in accordance with the Schedule of Assessments presented in 
Section 5. 
• The dosing period starts 14 days (±3 days) after the parent study at the Week 52 visit. 
Subjects should be consented and eligibility confirmed during the Week 52 visit of the 
main study.  Subjects will receive study drug every 2 weeks. The visit window for these 
visits is ±3 days. Each visit should be scheduled based on the previous visit  
Missed doses are not to be made up through extra visits. If a subject misses more than 
two infusions in an 8 week period, or two sequential infusions, the FibroGen Medical 
Monitor should be notified.  The reason for missed doses must be documented in the 
subject’s clinical record. 
• Vital signs (pulse, respiration, sitting BP, temperature) to be collected at every infusion 
visit: within 30 minutes pre-infusion, and within 30 minutes after completion of infusion. 
Physical exams should be performed in accordance with local standard of care (i.e., every 
24 weeks). Any significant findings will be reviewed by the Investigator to determine 
appropriate reporting of adverse events. 
• Muscle function tests including Loss of Ambulation (LoA) will be performed every 12 
weeks MFTs that cannot be performed or produce inadequate results according to test 
procedures during a specified visit should be performed by the next scheduled dosing 
visit.  Video QC will not be required during the OLE. 


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•
Weight will be performed every 12 weeks to make any weight based dose adjustments for
the next 12 week period.  Weight can be performed up to 2 weeks in advance of the 12
week interval visit.
•
Chemistry and hematology tests (Chemistry panel, CBC with differentials, and liver
function tests (LFTs)) should be completed centrally very 24 weeks.  Lab results should
be reviewed by the Investigator for clinically significant abnormalities and determine
appropriate reporting of adverse events.  A specialty lab will perform PK, HAHA, and
HAHA-NA testing for each specified blood draw timepoint in the OLE.  PK testing is
not optional in the OLE.Any immunogenic reactions, including drug-related
hypersensitivity or anaphylaxis, should have PK, HAHA, HAHA-NA drawn within 24
hours of reaction. (A window of “within 24 hours of reaction” could be at any point
following the reaction such as 30 minutes post-reaction but not to exceed 24 hours
following reaction).  The Tryptase sample should be drawn within 1 to 6 hours of
immunogenic reaction,  but all samples should at least be collected within 24 hours after
the anaphylactic episode.   For study visits in which  PK, HAHA, and HAHA-NA were
drawn as part of the Schedule of Assessments, if an Immunogenic reaction occurs,
additional samples still need to be taken within 24 hours of the immunogenic reaction.
This will not be considered optional for the subject unless there is local consideration
for total blood volume collection on the same day as a standard blood draw timepoint,
which could preclude the subject from having this collection take place within 24 hours.
See Appendix 2 for more detail.
•
NOTE: Patients that have an immunogenic reaction that occurs on the same date as a
routine study blood draw and weigh less than 30kg, must wait 24 hours prior to drawing
the corresponding PK, HAHA, HAHA-NA, and tryptase for immunogenicity per general
guidance on the lower limit total blood volume. However, local guidance and regulations
should be consulted regarding total blood volume to be drawn within a certain time frame
and takes precedence over any general recommendations.
•
Any assessments repeated as a part of main study, and all AEs prior to first dose in OLE
are considered as a part of the main study.
Subjects who complete the dosing period or early terminate will have a final follow-up visit 4 
weeks (±3 days) after the last dose of pamrevlumab as per the schedule of assessments.   
In the event that any visit is missed, assessments should be performed as soon after the 
missed visit as feasible. Missed infusions will not be replaced. 
Home Health Care 
During the OLE, the first three doses of the investigational product (IP) infusion must be 
administered at the study site. Home infusions for subsequent infusions may be an option as in 
the main study on a case by case basis as requested by the study site in geographic areas where 
such service could be feasibly provided.  


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Data collected during the extension period will be summarized descriptively along with the main 
study. 
4.   Statistical Considerations


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5. OLE Schedule of Assessments 
 
Q2 WEEKSU 
(U± 3 days) 
Q12 weeks 
(± 3 days) 
Q24 
weeks/EOT  
(± 3 days) 
Final Safety 
Follow-up (4 
Weeks (± 3 days) 
after Last 
treatment) EOS/ET 
Final Safety Phone 
Call (60 Days (+3 
days) after last 
treatment) 
Informed Consent & Assent/EligibilityPa 
 
 
 
 
 
Vital SignsPb 
x 
x 
x 
x 
 
Chemistry & Hematology (Central Labs) 
 
 
x 
x 
 
Muscle Function TestsPd 
 
x 
x 
xPc 
 
Physical Examination 
 
 
x 
x 
 
Weight/Weight Based Dose Adjustment 
 
xPf 
xPf 
 
 
Height 
 
 
x 
 
Specialty Labs (PK, HAHA, and HAHA-NA)  
 
 
x 
xP 
 
Pamrevlumab Infusion 
x 
x 
x 
 
 
AEs / SAEsg  
x 
x 
x 
x 
x 
Concomitant Medications  
x 
x 
x 
x 
x 
Abbreviations: AE = adverse event; EOS = End of Study; EOT = End of Treatment; ET= Early Termination;  
a. Prior to starting infusions and procedures for the OLE, subject must sign the OLE consent and be confirmed eligible at the Week 52 
visit of the main study. 
b. Vital signs (pulse, respiration, sitting BP, temperature) to be collected at every visit: within 30 minutes pre-infusion, and within 30 
minutes after completion of infusion. For EOS/ET, vitals to be completed one time only. 
c. Completed at the Early Termination visit only, MFTs do not have to be repeated if the last one was conducted within 8 weeks of this 
visit.   
d. Muscle Function Tests (MFTs): NSAA, 4SCV, 10M walk/run, TTSTAND, and Loss of Ambulation (LoA)  
e. Weight should be measured every 12 weeks to determine dose for the subsequent 12-week interval.  Weight for dose adjustments 
can be collected up to two weeks in advance. 
PK, HAHA and HAHA-NA sampling required at all blood draw visits in the OLE. PK is not optional in the OLE. See Appendix 2 for 
more details on immunogenic reaction blood draws. 


Signature Page for VV-CLIN-013270 v1.0
Signature Page for VV-CLIN-013270 v1.0
Approval Task
09-Nov-2022 15:06:58 GMT+0000

SAP_001.pdf: 
FibroGen, Inc. 
Confidential and Proprietary 
Page 1 of 20 
STATISTICAL ANALYSIS PLAN 
PROTOCOL TITLE: 
A Phase 3, Randomized, Double-Blind, Trial of Pamrevlumab 
(FG-3019) or Placebo in Combination with Systemic 
Corticosteroids in Ambulatory Subjects with Duchenne 
Muscular Dystrophy (DMD)
PROTOCOL NUMBER: 
Protocol FGCL-3019-094 (OLE) 
PROTOCOL AMENDMENT 
VERSION: 
4.0 (28 October 2022) 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
STUDY DRUG: 
Pamrevlumab 
INDICATION: 
Duchenne Muscular Dystrophy (DMD) 
SAP VERSION: 
Final V1.0 (Part 2 - OLE Period) 
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 #: NCT04632940


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
FibroGen, Inc. 
Confidential and Proprietary 
Page 2 of 20 
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: 
*Signature: see appended final page for 21CFR Part 11 compliant approval 
 
, FibroGen, Inc. 
Reviewed by: 
*Signatures: see appended final page for 21CFR Part 11 compliant approval 
, FibroGen, Inc. 
, FibroGen, Inc. 
 
, FibroGen, Inc. 
, FibroGen, Inc.  
 
, FibroGen, Inc. 
 
, FibroGen, Inc. 
 
 
 FibroGen, Inc.  
Signature Significance 
The following significance is lent to the signatures on the Approvals page of this document. 
Signatory 
Significance 
Initiator 
By signing, the author is attesting that the content of the document is 
complete and accurate. 
Reviewer 
By signing, the reviewer is attesting that the document’s approach and 
contents are compliant with the study protocol, all appropriate, regulatory 
requirements, and other significant guidelines. This individual(s) has 
reviewed the document for accuracy and completeness. 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
FibroGen, Inc. 
Confidential and Proprietary 
Page 3 of 20 
CHANGE HISTORY 
Version 
Date 
Description 
1.0 
18Dec2023 
Final approved version 
 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
FibroGen, Inc. 
Confidential and Proprietary 
Page 4 of 20 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ................................................................................................1 
SIGNATURE PAGE .......................................................................................................................2 
CHANGE HISTORY.......................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................6 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
INTRODUCTION ........................................................................................................8 
2. 
STUDY OBJECTIVE ...................................................................................................8 
3. 
STUDY DESIGN (OLE PERIOD) ..............................................................................8 
3.1. 
Enrollment to OLE Period ............................................................................................8 
3.2. 
Randomization ..............................................................................................................8 
3.3. 
Study Periods ................................................................................................................8 
4. 
STUDY ENDPOINTS (OLE) ......................................................................................9 
5. 
GENERAL STATISTICAL CONSIDERATIONS ......................................................9 
5.1. 
Statistical Methodology ................................................................................................9 
5.1.1. 
Analysis of Categorical Endpoints ...............................................................................9 
5.1.2. 
Analysis of Continuous Endpoints ...............................................................................9 
5.1.3. 
Analysis of Time-to-Event Endpoints ..........................................................................9 
5.1.4. 
Analysis of Spirometry Data ......................................................................................10 
5.2. 
Analysis Set ................................................................................................................10 
5.3. 
General Data Handling Rules and Presentation Specifications ..................................10 
5.3.1. 
Analysis Period ...........................................................................................................10 
5.3.2. 
Baseline Definitions ....................................................................................................10 
5.3.3. 
Formulas .....................................................................................................................10 
5.3.4. 
General Instructions of TLF .......................................................................................11 
5.3.5. 
Handling Dropouts and Missing Data ........................................................................11 
5.4. 
Interim Analysis and Data Monitoring Committee ....................................................11 
6. 
STATISTICAL ANALYSIS ......................................................................................11 
6.1. 
Subject Accountability and Disposition .....................................................................11 
6.2. 
Protocol Deviations ....................................................................................................11 
6.3. 
Demographics and Baseline Characteristics ...............................................................12 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
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Confidential and Proprietary 
Page 5 of 20 
6.4. 
Medical History ..........................................................................................................12 
6.5. 
Concomitant Medications ...........................................................................................12 
6.6. 
Treatments and Medications .......................................................................................12 
6.6.1. 
Study Drug Exposure ..................................................................................................12 
6.6.2. 
Treatment Compliance ................................................................................................13 
6.7. 
Efficacy Analysis ........................................................................................................13 
6.7.1. 
Primary Endpoint Estimand and Analysis ..................................................................13 
6.7.1.1. 
Estimand Strategy .......................................................................................................13 
6.7.1.2. 
Population of Interest ..................................................................................................13 
6.7.1.3. 
Intercurrent Event Handling Strategy .........................................................................13 
6.7.1.4. 
Analysis Variable ........................................................................................................13 
6.7.1.5. 
Population Summary for Treatment Comparison .......................................................13 
6.8. 
Safety Analysis ...........................................................................................................13 
6.8.1. 
Adverse Events (AE) ..................................................................................................13 
6.8.2. 
Clinical Laboratory Parameters ..................................................................................14 
6.8.3. 
Vital Signs ..................................................................................................................14 
6.9. 
Immunogenicity Analysis ...........................................................................................14 
6.9.1. 
Terms and Definitions ................................................................................................14 
6.9.1.1. 
Sample ADA Status: ...................................................................................................14 
6.9.1.2. 
Subject ADA Status: ...................................................................................................14 
6.9.2. 
Statistical Analysis for Characterization of ADA Immune Response ........................15 
6.9.2.1. 
Incidence of ADA .......................................................................................................15 
6.9.2.2. 
ADA Titer Kinetics .....................................................................................................15 
7. 
CHANGES FROM PROTOCOL ...............................................................................16 
8. 
REFERENCE .............................................................................................................17 
9. 
APPENDICES ............................................................................................................18 
Appendix 1. Analysis Visit Windows .........................................................................................19 
 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
FibroGen, Inc. 
Confidential and Proprietary 
Page 6 of 20 
LIST OF TABLES 
Table 1: 
Analysis Visit Window for Vital Signs ......................................................................19 
Table 2: 
Analysis Visit Window for MFT and Weight* ..........................................................19 
Table 3: 
Analysis Visit Window for Labs, and Physical Examinations ...................................19 
Table 4: 
Analysis Visit Window for Immunogenicity Data .....................................................19 
 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
FibroGen, Inc. 
Confidential and Proprietary 
Page 7 of 20 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
4SCV 
4-Stair Climb Velocity 
ADA 
Antidrug Antibody 
AE 
Adverse Event 
BSA 
Body Surface Area 
DMD 
Duchenne Muscular Dystrophy 
DMC 
Data Monitoring Committee 
FG-3019 
FibroGen-3019 (Recombinant Human Monoclonal Antibody), Pamrevlumab 
IGS 
Immunogenicity Analysis Set 
IV 
Intravenous 
LoA 
Loss of Ambulation 
MMRM 
Mixed Model for Repeated Measures 
NAb 
Neutralizing Antibody 
NSAA 
NorthStar Ambulatory Assessment 
OLE 
Open Label Extension 
PEY 
Patient Exposure Years 
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event 
TESAE 
Treatment Emergent Serous Adverse Event 
TLF 
Tables, Listings, and Figures 
TTSTAND 
Time to Stand 
 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
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Confidential and Proprietary 
Page 8 of 20 
1. 
INTRODUCTION 
This statistical analysis plan (SAP) is for the pre-specified reporting of study results for protocol 
FGCL-3019-094, amendment 4.0. Specifications of tables, data listings, and figures (TLFs) are 
contained in a separate document. This is Part 2 of the SAP, which documents the planned 
analyses for the open-label extension (OLE) period. For the purposes of this document, 
references to Part 1 of the SAP refer to the SAP for the randomized, placebo-controlled portion 
of the study. 
In this document, only new definitions and rules will be described; the same definitions and rules 
described in the SAP for the main study will not be repeated. 
2. 
STUDY OBJECTIVE 
The overall objective of this Phase 3 registration-enabling study is to evaluate the efficacy and 
safety of 35 mg/kg intravenous (IV) infusions of pamrevlumab as compared to placebo in 
ambulatory subjects with Duchenne Muscular Dystrophy (DMD) over 52 weeks.   The objective 
of the optional open-label, single arm extension is to evaluate long-term efficacy and safety of 
pamrevlumab in DMD subjects. 
3. 
STUDY DESIGN (OLE PERIOD) 
3.1. 
Enrollment to OLE Period  
Subjects who complete the Week 52 visit of the main study (regardless of the number of study 
drug infusions received) will be eligible to participate in the optional OLE period of the study 
that offers continuing access to pamrevlumab regardless of randomization assignment in the 
main study.  Subjects will be considered as having entered the OLE study if they have received 
at least one dose of the study drug during the OLE period. 
3.2. 
Randomization 
Randomization is not applicable for the OLE period. All patients will receive IV pamrevlumab 
35 mg/kg. 
3.3. 
Study Periods 
• Optional, OLE period of pamrevlumab:  
o Access to pamrevlumab will be available until the last subject completes 
52 weeks of treatment in the OLE period, or pamrevlumab is commercially 
available, or the Sponsor decides to end the OLE period, whichever occurs first.  
• Follow-up period/final safety assessments:   
o 28 days after the last dose 
o 60 days after the last dose: follow-up phone call, for a final safety assessment   


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
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Confidential and Proprietary 
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4. 
STUDY ENDPOINTS (OLE)  
The following efficacy and safety assessments will be collected only as standard-of-care per each 
investigational site’s real-world practice and descriptively presented during the OLE period: 
Efficacy assessments: 
• Change in NorthStar Ambulatory Assessment (NSAA) total score 
• Change in 4-stair climb Velocity (4SCV) assessment 
• Change in the 10-meter walk/run test 
• Change in Time to Stand (TTSTAND) 
• Time of Loss of Ambulation (LoA) assessment  
• Cumulative Loss of Function Analysis for NSAA 
• Proportions of subjects in 10-meter walk/run test > 10 seconds 
 
Safety assessments: 
• Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse 
events (TESAEs), clinically significant laboratory test abnormalities, discontinuation 
of treatment due to TEAEs, and hypersensitivity/anaphylactic reactions 
• Number and percentage of subjects with hospitalizations due to any serious adverse 
events with pulmonary and/or cardiac cause(s) 
• Number and percentage of subjects with bone fractures 
• Annualized height velocity from Baseline of OLE  
5. 
GENERAL STATISTICAL CONSIDERATIONS 
5.1. 
Statistical Methodology 
All data collected will be included in the data listings. All analyses will be performed using 
SAS® Version 9.4 or higher. 
5.1.1. 
Analysis of Categorical Endpoints 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. 
5.1.2. 
Analysis of Continuous Endpoints 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. 
5.1.3. 
Analysis of Time-to-Event Endpoints 
Kaplan-Meier curves for time-to-event endpoints will be plotted as appropriate. 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
FibroGen, Inc. 
Confidential and Proprietary 
Page 10 of 20 
5.1.4. 
Analysis of Spirometry Data 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. 
5.2. 
Analysis Set 
The Safety Analysis Set - OLE (SAF-OLE) includes all subjects who have received at least one 
study medication in the OLE period. Subjects will be analyzed according to the previous 
treatment actually received in the main study.  
All analysis in OLE will be performed on SAF-OLE unless otherwise specified. 
The Immunogenicity Analysis Set (IGS) contains all the antidrug antibody (ADA) evaluable 
patients, who are in the SAF-OLE analysis set with at least one ADA/neutralizing antibody 
(NAb) sample (with reportable results) taken pre-treatment (i.e., a baseline sample) and at least 
one ADA sample (with reportable result) taken post-treatment in the OLE period. 
5.3. 
General Data Handling Rules and Presentation Specifications 
5.3.1. 
Analysis Period 
• The safety analysis will be based on the on-study period which is defined as from 
Day 1 in the OLE period up to the end of the entire study, regardless of patients’ 
treatment status. 
• Efficacy analyses will be based on the entire study period which includes both the 
main study period and the OLE period. 
5.3.2. 
Baseline Definitions 
• Baseline for the OLE period is defined as the last acceptable assessment on or prior to 
the first dosing date in the OLE period.  
• Baseline for main study period is defined the same as in SAP Part 1 for the 
randomized treatment period.  
5.3.3. 
Formulas 
• Study Day Calculation 
− The day when a subject receives the first dose of study drug in the OLE period is 
designated as Day 1 in OLE.  
− Study day of an assessment/procedure is calculated as follows. 
 
For assessments or procedures on Day 1 or later,  
Study day = assessment/procedure date – Day 1 date + 1. 
 
For assessments or procedures earlier than Day 1,  
Study day = assessment/procedure date – Day 1 date. 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
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Confidential and Proprietary 
Page 11 of 20 
• Follow the same formulas as described in SAP Part 1 for the randomized treatment 
period: 
− Body surface area (BSA)  
− Change from Baseline  
• Patient exposure years (PEY) (on pamrevlumab in OLE period) 
− PEY = Number of subjects × Average Duration of Exposure (year), where 
duration of exposure for each subject is (date of last non-zero dose on 
pamrevlumab – date of first dose in OLE period on pamrevlumab + 1)/365.25. 
5.3.4. 
General Instructions of TLF 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. 
Summary tables will be presented for each treatment group in the main study and all subjects 
pooled in the OLE period. 
Long-term efficacy data will be analyzed during the entire study period which includes both the 
main study period and the OLE period and safety data will be summarized only in the OLE 
period for subjects who entered OLE and got dosed. 
5.3.5. 
Handling Dropouts and Missing Data 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. 
5.4. 
Interim Analysis and Data Monitoring Committee 
In addition to routine safety monitoring, an independent Data Monitoring Committee (DMC) 
will be established to review safety data on an ongoing basis. A DMC charter will establish the 
procedures, meeting frequency, and scope of responsibilities of the committee.  
This study has no planned or pre-specified interim analysis for either efficacy or futility.  
6. 
STATISTICAL ANALYSIS 
6.1. 
Subject Accountability and Disposition 
The number (%) of subjects who entered the OLE period, discontinued prematurely from 
treatment, discontinued prematurely from study, and reasons for premature discontinuation will 
be presented for each previous treatment group in the main study and all subjects pooled. 
Enrollment will also be summarized by study site. 
6.2. 
Protocol Deviations 
The number and percentage of subjects with important protocol deviations will be categorized 
and tabulated as appropriate. COVID-19 related important protocol deviations will be 
summarized in a separate table. All protocol deviations will be finalized prior to database lock. 


FGCL-3019-094 (LENANTOS - 2)  
Statistical Analysis Plan  
Final V1.0 (Part 2 - OLE Period)   
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Confidential and Proprietary 
Page 12 of 20 
6.3. 
Demographics and Baseline Characteristics 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. 
6.4. 
Medical History 
Medical history summary will be presented for the OLE period. 
6.5. 
Concomitant Medications 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. No 
prior medications summary will be presented. 
6.6. 
Treatments and Medications 
6.6.1. 
Study Drug Exposure 
Study treatment will be summarized for the main study, OLE period, and entire study, 
respectively. SAF-OLE in the main study will be used for summaries of the main study and the 
entire study (Main + OLE Periods). 
• Duration of exposure in Main Study = date of last non-zero dose in Main Study– date 
of the first dose in Main Study + 1.  
• Duration of exposure in the OLE period = date last non-zero dose in the OLE period – 
date of the first dose in the OLE period + 1. 
• Duration of entire study treatment exposure (Main + OLE Periods) = date last non-
zero dose in study – date of the first dose in study + 1. 
Duration of study treatment in the OLE period will be summarized as a continuous variable and 
be tabulated by the categories as follows: 
• <26 Weeks 
• 26 to <52 Weeks 
• 52 to <78 Weeks 
• 78 to <104 Weeks 
• 104 to <130 Weeks 
• ≥130 Weeks  
Number of infusions is defined as the number of non-zero dose infusions. 
The following dose administration parameters: 
• Total number of infusions in the OLE period (≤12, 13-24, 25-36, 37-48, 49-60, >60)  
• Overall average infusion doses (in mg/kg) in the OLE period 
• Whether infusion was interrupted and reason for interruption in the OLE period 


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6.6.2. 
Treatment Compliance 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period.  
Compliance will be derived for the main study, OLE period, and entire study, respectively.  
6.7. 
Efficacy Analysis 
All analyses for efficacy endpoints will be performed for the SAF-OLE during the on-study 
period unless noted otherwise.  
6.7.1. 
Primary Endpoint Estimand and Analysis 
6.7.1.1. 
Estimand Strategy  
The primary estimand is intended to provide a population-level efficacy assessment of the 
pamrevlumab on a continuous endpoint, regardless of participant compliance with the 
investigational product  dosing. 
6.7.1.2. 
Population of Interest 
All subjects in SAF-OLE. 
6.7.1.3. 
Intercurrent Event Handling Strategy 
Treatment policy strategy will be used for any intercurrent event. No imputation on missing data. 
6.7.1.4. 
Analysis Variable 
Change from baseline in all NSAA assessments (scheduled and unscheduled) in the OLE period, 
including scheduled, unscheduled, and available assessments after treatment discontinuation, will 
be included in the analysis. 
6.7.1.5. 
Population Summary for Treatment Comparison  
Efficacy parameters, including change from baseline in 4SCV, the 10-meter walk/run test, 
TTSTAND, Time of LoA, and proportions of subjects in 10-meter walk/run test >10 seconds 
will be analyzed at Week 24, Week 36, and Week 48 in the OLE period using Mixed Model for 
Repeated Measures (MMRM) approach with fixed effects for treatment, visit (as a factor), 
treatment-by-visit interaction, and covariates (baseline values). The results at each analysis visit 
from baseline of the main study till the last visit with evaluable assessments in the OLE period 
will be presented. 
6.8. 
Safety Analysis 
The safety analyses will be performed for the SAF-OLE in the OLE period.  
6.8.1. 
Adverse Events (AE) 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period with 
additional PEY for OLE period on pamrevlumab provided. 


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6.8.2. 
Clinical Laboratory Parameters 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. The 
analysis visit window is defined in Appendix 1. 
6.8.3. 
Vital Signs 
Follow the same guidelines as described in SAP Part 1 for the randomized treatment period. The 
analysis visit window is defined in Appendix 1. 
6.9. 
Immunogenicity Analysis 
Analysis of immunogenicity data will be based on IGS. Analysis dataset and data listing will 
include all available ADA samples. The following terms and definitions are implemented. 
6.9.1. 
Terms and Definitions 
6.9.1.1. 
Sample ADA Status: 
• Baseline ADA-positive sample: ADA is detected in the last sample before initiation 
of treatment. 
• Baseline ADA-negative sample: ADA is not detected in the last sample before 
initiation of treatment. 
• Treatment-emergent ADA-Positive: Meets definition of treatment-induced or 
treatment-boosted ADA. After initiation of treatment,  
− Treatment-induced ADA-Positive: A post-treatment positive ADA is detected in 
a subject for whom pre-treatment ADA assessment is either negative or not 
assessable, or  
− Treatment-boosted ADA-Positive: Pre-existing ADA were boosted to a higher-
level following study treatment, i.e., pre-treatment positive ADA titer was boosted 
by at least 2 dilution steps (4-fold) following study treatment. 
• ADA-negative sample: After initiation of treatment, ADA is not treatment-emergent 
ADA-positive. 
Next, using the sample ADA status, subject ADA status is defined. 
6.9.1.2. 
Subject ADA Status: 
• Baseline ADA-positive subject: A subject with baseline ADA-positive sample.  
• ADA-positive subject:  An evaluable subject with at least one treatment-emergent 
ADA sample at any time during the study. 
• Neutralizing-positive: At least one treatment-emergent ADA-positive sample with 
neutralizing antibodies detected (if available). 
• ADA-negative subject: An evaluable patient without a treatment-emergent 
ADA-positive sample during the study. 


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6.9.2. 
Statistical Analysis for Characterization of ADA Immune Response 
6.9.2.1. 
Incidence of ADA 
• Percentage of treatment-emergent ADA patients for the defined study period, where 
the denominator is the number of ADA evaluable patients in the respective treatment 
arm and/or subgroup. 
• Number (%) of subjects will be reported for the following parameters based on 
evaluable subjects: 
− Baseline ADA-positive 
− ADA-positive (Treatment-induced, Treatment-boosted) 
− Neutralizing Positive (if available) 
− ADA-negative 
• ADA prevalence: Percentage of treatment-emergent ADA patients at any given 
timepoint, where the denominator is the number of ADA evaluable patients in the 
respective treatment arm and/or subgroup at that timepoint. 
• A listing of all ADA assessments will be provided.  
• Additionally, a separate listing of ADA assessments for all NAb-positive subjects will 
be provided (if available). 
6.9.2.2. 
ADA Titer Kinetics  
All ADA-positive subjects will be included in the analysis. 
• Summary statistics of subject-level ADA titers using the maximum titer value within 
an ADA positive subject will be presented for baseline ADA-negative subjects and 
baseline ADA positive subjects. The median, mean (standard deviation [SD]), 
interquartile range, range of the maximum titers, and geometric mean (SD) will be 
reported. For ADA-positive subjects with baseline ADA-positive sample, the median 
and interquartile range of the fold increase from baseline in titer (ratio of maximum 
post-baseline titer to baseline titer) will also be reported. Graphical presentation of the 
summary data may be provided using boxplots, as appropriate. 
• For sample-level ADA titers, boxplots of ADA titers at each assessment timepoint 
will be provided, as appropriate, to demonstrate whether the ADA levels tend to 
change over time during the treatment, along with ADA incidence at each assessment 
timepoint. 
• Spider plots may be considered to show the trend of ADA titer over time for subjects 
with ≥ 5 ADA results by splitting subjects into multiple spider plots (eg, ≈ ≤10 per 
plot, approximately. 
 


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7. 
CHANGES FROM PROTOCOL 
• Cumulative loss of function analysis (Section 4) was added as an efficacy endpoint. 
• Proportions of subjects in 10-meter walk/run test was added as an efficacy endpoint. 
• Annualized height velocity from Baseline of OLE was not analyzed due to the limited 
collection of data. 
 
 


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8. 
REFERENCE 
1. Annexstad EJ, Lund-Petersen I, Rasmussen M. (2014) Duchenne muscular dystrophy. 
Tidsskr Nor Laegeforen. 134(14):1361-1364. 
2. Mayer OH, Finkel RS, Rummey C, et al. (2015) Characterization of pulmonary function 
in Duchenne Muscular Dystrophy. Pediatr Pulmonol. 50(5):487-494 
3. Finder J, Mayer OH, Sheehan D, et al. (2017) Pulmonary endpoints in Duchenne 
Muscular Dystrophy: A workshop summary. Am J Respir Crit Care Med. 
196(4):512-519. 
4. Hagenbuch SC, Gottliebson WM, Wansapura J, et al. (2010) Detection of progressive 
cardiac dysfunction by serial evaluation of circumferential strain in patients with 
Duchenne Muscular Dystrophy. Am J Cardiology. 105(10):1451-1455 
5. Ricotti V, Selby V, Ridout D, et al. (2019) Respiratory and upper limb function as 
outcome measures in ambulant and non-ambulant subjects with Duchenne muscular 
dystrophy: A prospective multicentre study. Neuromuscul Disord. 29(4):261-268. 
6. McDonald CM, Henricson EK, Abresch A, et al. (2018) Long-term effects of 
glucocorticoids on function, quality of life, and survival in patients with Duchenne 
muscular dystrophy: a prospective cohort study. Lancet. 391(10119):451-461. 
7. Supplement to: McDonald CM, Henricson EK, Abresch RT, et al. (2018) Long-term 
effects of glucocorticoids on function, quality of life, and survival in patients with 
Duchenne muscular dystrophy: a prospective cohort study. Lancet. 391(10119):451-461. 
8. Sun G, Haginoya K, Wu Y, et al. (2008) Connective tissue growth factor is 
overexpressed in muscles of human muscular dystrophy. J Neurol Sci. 267(1-2):48-56.  
9. Szigyarto CA and Spitali P. (2018) Biomarkers of Duchenne muscular dystrophy: current 
findings. Degener Neurol Neuromuscul Dis. 8:1-13 
10. Yiu EM and Kornberg AJ. (2015) Duchenne muscular dystrophy. J Paediatr Child 
Health. 51(8):759-764.  
11. Zhou L and Lu H. (2010) Targeting fibrosis in Duchenne muscular dystrophy. 
J Neuropathol Exp Neurol. 69(8):771-776. 
12. Meier T, Rummey C, Leinonen M, et al. (2017) Characterization of pulmonary function 
in 10-18 year old patients with Duchenne muscular dystrophy. Neuromuscul Disord. 
27(4):307-314  
 


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9. 
APPENDICES 


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APPENDIX 1. ANALYSIS VISIT WINDOWS 
Analysis visits are defined by the windows that will have the widths of the corresponding 
assessments centered at the scheduled time. Unscheduled visits within a visit window defined 
below will be grouped into the closest scheduled visits based on the visit date. 
Table 1: 
Analysis Visit Window for Vital Signs 
Analysis Visit 
Target Day in OLE 
Start Day 
End Day 
Baseline 
See Section 5.3.2 
EX-Day 1 
1 
1 
1 
EX-Week k 
K=1,2,3,… 
7*2k+1 
(End Day)k-1+1 
7*2k+8 
Table 2: 
Analysis Visit Window for MFT and Weight* 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
See Section 5.3.2 
EX-Day 1 
1 
1 
1 
EX-Week k 
K=1,2,3,… 
7*12k+1 
(End Day)k-1+1 
(7*12k+1)+12*7/2 
* Weight is collected during the dose adjustment visit or can be done up to two weeks in advance.
Table 3: 
Analysis Visit Window for Labs, and Physical Examinations 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
See Section 5.3.2 
EX-Day 1 
1 
1 
1 
EX-Week k 
K=1,2,3,… 
7*24k+1 
(End Day)k-1+1 
(7*24k+1)+24*7/2 
Table 4: 
Analysis Visit Window for Immunogenicity Data 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Assessment prior to first dose in OLE 


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EX-Week k 
K=1,2,3,… 
7*24k+1 
(End Day)k-1+1 
(7*24k+1)+24*7/2 
 


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Signature Page for VV-CLIN-013281 v2.0
Approval Task
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18-Jan-2024 07:01:26 GMT+0000
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Statistical Analysis Plan 
TITLE PAGE 
PROTOCOL TITLE: 
A Phase 3, Randomized, Double-Blind, Trial of 
Pamrevlumab (FG-3019) or Placebo in Combination 
with Systemic Corticosteroids in Ambulatory 
Subjects with Duchenne Muscular Dystrophy 
(DMD) 
PROTOCOL NUMBER: 
Protocol FGCL-3019-094 
Amendment 4: 28 October, 2022 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
STUDY DRUG: 
Pamrevlumab 
INDICATION: 
Duchenne Muscular Dystrophy (DMD) 
SAP VERSION 
Final 2.0  
RELEASE DATE 
9 August, 2023 
 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and proprietary to FibroGen, Inc. No 
part of this document or any of the information contained herein may be transmitted, disclosed, 
shared, reproduced, published or utilized by any persons without prior written authorization by 
FibroGen, Inc.


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


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CHANGE HISTORY 
Version 
Date 
Description 
Final 1.0 
25JUL2023 
Initial version 
Final 2.0 
9AUG2023 
Removed analysis related to biceps brachii because it 
is not included in the protocol. 
Added a statement on the baseline definition for MFT 
assessments in “Changes from Protocol” section.  
Replaced “infusion-related reactions” with “infusion 
reactions”. 
 
 
 
 


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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
SIGNATURES AND APPROVALS ...............................................................................................2 
CHANGE HISTORY.......................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................7 
LIST OF FIGURES .........................................................................................................................7 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1. 
INTRODUCTION ......................................................................................................10 
2. 
STUDY OBJECTIVES ..............................................................................................10 
3. 
STUDY DESIGN .......................................................................................................10 
3.1. 
Overview .....................................................................................................................10 
3.2. 
Study Population .........................................................................................................10 
3.3. 
Sample Size Determination ........................................................................................10 
3.4. 
Randomization and Treatment Assignment ................................................................10 
3.5. 
Study Periods ..............................................................................................................11 
3.6. 
Study Assessments......................................................................................................12 
4. 
STUDY ENDPOINTS ................................................................................................13 
4.1. 
Primary Endpoint ........................................................................................................13 
4.2. 
Secondary Endpoints ..................................................................................................13 
4.3. 
Safety Assessments .....................................................................................................13 
4.4. 
Exploratory Endpoints ................................................................................................13 
4.5. 
Pharmacokinetics/pharmacodynamics (PK/PD) assessment ......................................13 
5. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................13 
5.1. 
General Conventions ..................................................................................................13 
5.1.1. 
Analysis for Categorical Endpoints ............................................................................14 
5.1.2. 
Analysis for Continuous Endpoints ............................................................................14 
5.2. 
Analysis Sets ...............................................................................................................14 
5.2.1. 
Intent-to-Treat Set (ITT) .............................................................................................14 
5.2.2. 
Per-Protocol Set (PPS) ................................................................................................14 
5.2.3. 
Safety Analysis Set (SAF) ..........................................................................................15 
5.2.4. 
Immunogenicity Analysis Set (IGS) ...........................................................................15 


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5.3. 
General Data Handling Rules and Presentation Specifications ..................................15 
5.3.1. 
Analysis Period ...........................................................................................................15 
5.3.2. 
Baseline and Change from Baseline Definitions ........................................................15 
5.3.3. 
Study Day Calculation ................................................................................................15 
5.3.4. 
General Instructions on TFLs .....................................................................................16 
5.3.5. 
Handling Dropouts and Missing Data ........................................................................16 
5.4. 
Interim Analysis and Data Monitoring Committee ....................................................16 
5.5. 
Analysis Visit Windows .............................................................................................16 
6. 
STATISTICAL ANALYSES .....................................................................................17 
6.1. 
Subject Enrollment and Disposition ...........................................................................17 
6.1.1. 
Eligibility ....................................................................................................................17 
6.1.2. 
Subject Accountability and Disposition .....................................................................17 
6.2. 
Important Protocol Deviations ....................................................................................17 
6.3. 
Demographics and Baseline Characteristics ...............................................................18 
6.3.1. 
Demographics and Baseline Characteristics ...............................................................18 
6.3.2. 
Baseline DMD Disease Characteristics ......................................................................18 
6.3.3. 
Medical History ..........................................................................................................20 
6.4. 
Prior and Concomitant Medications ...........................................................................20 
6.5. 
Study Drug Exposure and Treatment Compliance .....................................................20 
6.5.1. 
Study Drug Exposure ..................................................................................................20 
6.5.2. 
Treatment Compliance ................................................................................................21 
6.6. 
Efficacy Analyses .......................................................................................................21 
6.6.1. 
Primary Endpoint Estimand and Analysis ..................................................................22 
6.6.2. 
Secondary Endpoints Estimands and Analyses ..........................................................28 
6.6.3. 
Exploratory Endpoint Analyses ..................................................................................30 
6.6.4. 
Subgroup Analyses of the Specified Endpoints..........................................................31 
6.7. 
PK Analyses ................................................................................................................31 
6.8. 
Safety Analyses ..........................................................................................................31 
6.8.1. 
Adverse Events ...........................................................................................................31 
6.8.2. 
Clinical Laboratory Assessments ...............................................................................32 
6.8.3. 
Vital Signs ..................................................................................................................33 
6.8.4. 
Physical Examination .................................................................................................34 
6.8.5. 
Electrocardiogram .......................................................................................................34 


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6.8.6. 
Special Safety Events .................................................................................................34 
6.8.7. 
Bone Fractures ............................................................................................................34 
6.8.8. 
Subgroup Analyses of Safety Endpoints ....................................................................35 
6.9. 
Biomarker Endpoint Analysis .....................................................................................35 
6.10. 
Immunogenicity Analysis ...........................................................................................35 
6.10.1. 
Terms and Definitions ................................................................................................35 
6.10.2. 
Statistical Analysis for Characterization of ADA Immune Response ........................36 
6.10.3. 
Clinical Implication of ADA Immune Response ........................................................37 
7. 
CHANGES FROM PROTOCOL ...............................................................................38 
8. 
REFERENCES ...........................................................................................................39 
9. 
APPENDICES ............................................................................................................40 
APPENDIX 1. HANDLING MISSING/INCOMPLETE DATES .............................................41 
APPENDIX 2. ANALYSIS VISIT WINDOWS ........................................................................44 
APPENDIX 3. NORTH STAR AMBULATORY ASSESSMENT (NSAA) .............................47 
APPENDIX 4. LABORATORY TEST CTCAE CRITERIA .....................................................49 
APPENDIX 5. GENERAL SPECIFICATIONS FOR TABLES, LISTINGS, FIGURES .........51 
1. 
Software Used .............................................................................................................51 
2. 
General ........................................................................................................................51 
3. 
Page Layout ................................................................................................................51 
4. 
Titles and Footnotes ....................................................................................................52 
5. 
Table, Figure, Listing Metadata ..................................................................................52 
6. 
Significant Digits of Summary Statistics ....................................................................53 
7. 
Figure Specifications ..................................................................................................53 
APPENDIX 6. CHINA CDE REQUIREMENTS.......................................................................55 
 


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LIST OF TABLES 
Table 1: 
Testing Sequence of Primary and Secondary Endpoints ............................................22 
Table 2: 
Laboratory Tests .........................................................................................................32 
Table 3: 
Criteria for Potentially Clinically Significant Vital Signs ..........................................34 
Table 4: 
Analysis Date Derivation Rules for Missing/Incomplete AE Onset Date ..................41 
Table 5: 
Analysis Date Derivation Rules for Missing/Incomplete AE Stop Date ....................42 
Table 6: 
Analysis Visit Window for Vital Signs ......................................................................44 
Table 7: 
Analysis Visit Window for Physical Examination .....................................................45 
Table 8: 
Analysis Visit Window for Pulmonary Function Tests (PFT) ...................................45 
Table 9: 
Analysis Visit Window for Muscle Function Tests (MFT) ........................................45 
Table 10: Analysis Visit Window for Laboratory Tests .............................................................46 
Table 11: Analysis Visit Window for Immunogenicity Data .....................................................46 
Table 12: Specifications for Page Layout ...................................................................................51 
Table 13:  Significant Digits of Summary Statistics ...................................................................53 
 
LIST OF FIGURES 
Figure 1: 
FGCL-3019-094 Study Schema .................................................................................11 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
Anti-Drug Antibody 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
CBC 
Complete Blood Count 
CDE 
Center for Drug Evaluation (China) 
CRF 
Case Report Form 
CS 
Clinically Significant 
CSR 
Clinically Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBL 
Database Lock 
DMD 
Duchenne Muscular Dystrophy 
DMC 
Data Monitoring Committee 
DVA 
Duchenne Video Assessment 
ECG 
Electrocardiogram 
EOS 
End of Study 
EOT 
End of Treatment 
FG-3019 
FibroGen-3019 (Recombinant Human Monoclonal Antibody), Pamrevlumab 
HAHA 
Human Anti-Human Antibody 
IP 
Investigational Product 
ITT 
Intent-to-Treat 
IV 
Intravenous 
LLN 
Lower Limit of Normal 
LoA 
Loss of Ambulation 
LVEF% 
Left Ventricular Ejection Fraction Percentage 


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Abbreviation 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFT 
Muscle Function Tests 
MI ANCOVA 
Multiple Imputation ANCOVA 
MMRM 
Mixed Model Repeated Measures 
MRI 
Magnetic Resonance Imaging 
Nab 
Neutralizing Antibody 
NCI 
National Cancer Institute 
NSAA 
North Star Ambulatory Assessment 
OLE 
Open Label Extension 
PD 
Pharmacodynamics 
PFT 
Pulmonary Function Test 
PK 
Pharmacokinetic 
ppFVC 
Percent Predicted Forced Vital Capacity 
ppPEF 
Percent Predicted Peak Expiratory Flow 
PT 
Preferred Term 
aPTT 
Activated Partial Prothrombin Time 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SE 
Standard Error 
SoA 
Schedule of Assessments 
SOC 
System Organ Class 
TEAE 
Treatment-emergent Adverse Event 
TESAE 
Treatment-emergent Serous Adverse Event 
TFLs 
Tables, Figures and Listings 
TTSTAND 
Time to Stand (from Supine) 
ULN 
Upper Limit of Normal 
WHODD 
World Health Organization Drug Dictionary 
4SCV 
4-Stair Climb Velocity 


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1. 
INTRODUCTION 
This statistical analysis plan (SAP) provides a more technical and detailed elaboration of the 
statistical analyses of study data as specified in the Study Protocol FGCL-3019-094 
Amendment 4, 28 October 2022. Specifications of tables, figures, and listings (TFLs) are 
contained in a separate document.  The statistical analyses and summary tabulations described in 
this SAP provide the basis for the results sections of the clinical study report (CSR) for this 
study. The SAP will be finalized and signed off prior to database lock (DBL). Any major 
modification of this SAP after the signoff will be documented in a SAP amendment or the CSR. 
This SAP is only for the main study period. The Open Label Extension (OLE) will have a 
separate SAP. A population pharmacokinetic (PK) analysis, as well as an exposure-response 
analysis, will be defined in a separate PK analysis plan.  
Based on regional regulatory filing needs, region specific populations will be analyzed following 
this same SAP. Refer to Appendix 6 if regulatory submission in China is pursued. 
2. 
STUDY OBJECTIVES 
The overall objective of this trial is to evaluate the efficacy and safety of pamrevlumab versus 
placebo in combination with systemic corticosteroids administered every two weeks in 
ambulatory subjects with Duchenne muscular dystrophy (age 6 to <12 years).   
3. 
STUDY DESIGN 
3.1. 
Overview 
Study FGCL-3019-094 is a Phase 3, randomized, double-blind, placebo-controlled multi-center 
trial to evaluate the efficacy and safety of pamrevlumab in ambulatory subjects with DMD over a 
52-week period.  
3.2. 
Study Population 
Approximately 70 subjects will be enrolled in this trial, globally.  
3.3. 
Sample Size Determination 
With a total sample size of 70 subjects allocated in a 1:1 ratio between the pamrevlumab arm and 
the placebo arm, the study will achieve at least 80% power to detect an effect size of 0.705 
(assuming a treatment difference of 6.0 points in linearized total North Star Ambulatory 
Assessment [NSAA] with common standard deviation of 8.5, or a treatment difference of 1.91 in 
raw total NSAA with common standard deviation of 2.71) in the mean change from baseline in 
the total score of NSAA with a one-sided significance level (alpha) of 0.025. 
3.4. 
Randomization and Treatment Assignment 
Subjects will be randomized by a 1:1 ratio to one of the two study treatment arms as follows:  


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• Arm A: pamrevlumab 35 mg/kg IV Q2 weeks + systemic deflazacort or equivalent 
potency of corticosteroids administered orally. 
• Arm B: matching placebo IV Q2 weeks + systemic deflazacort or equivalent potency 
of corticosteroids administered orally. 
Randomization will be stratified by exon 44 deletion (Yes/No). 
3.5. 
Study Periods 
This study consists of the following study periods (Figure 1): 
• Main (double-blind, placebo-controlled) study period: 
− Screening period: Up to 4 weeks 
− Treatment period: 52 weeks 
• Optional, open label extension (OLE) period: 
Subjects who complete week 52 of the main study (regardless of the number of study 
drug infusions received) will be eligible to participate in the OLE where all subjects will 
be treated with pamrevlumab. If a subject discontinues the main study early for any 
reason they will not be eligible for inclusion in the OLE. 
• Follow-up period/final safety assessment: 
− 28 days after last dose: scheduled visit 
− 60 days after last dose: follow-up phone call, for a final safety assessment 
Subjects who discontinue study treatment for any reason will be encouraged to return to the 
investigative site to complete final safety and efficacy assessments. 
A schematic overview of the study is provided in Figure 1. A detailed overview of assessments 
and the timing of assessments are provided in Appendix 1. 
 
Figure 1: 
FGCL-3019-094 Study Schema 
 
Abbreviations: EOS= End of Study, ET=Early Termination 
a) Subjects who discontinue the study early, for any reason, will complete an early termination visit 28 days (+/- 3 
Days) and a final safety follow-up phone call 60 days (+ 3 days) after the last infusion.  


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3.6. 
Study Assessments 
The intent of this study is to evaluate the efficacy and safety profile of pamrevlumab in 
combination with systemic corticosteroids in subjects with ambulatory Duchenne muscular 
dystrophy (age 6 to <12 years).  
The following assessments will be assessed by following the schedules defined in the protocol 
(SoA in the Appendix of the protocol). 
• North Star Ambulatory Assessment (NSAA)  
• 4-Stair Climb Velocity (4SCV)  
• 10-Meter Walk/Run Test 
• Time to Stand (TTSTAND) 
• Time to Loss of Ambulation (LoA) 
• Duchenne Video Assessment (DVA) 
• Percent predicted FVC (ppFVC) and percent predicted Peak Expiratory Flow (ppPEF) 
assessed by spirometry 
• Lower extremities vastus lateralis muscle fibrosis score assessed by magnetic resonance 
imaging (MRI) 
Safety assessments will be assessed throughout the study and in accordance with the SoA in the 
protocol, including but not limited to, adverse events (AEs), concomitant medications, laboratory 
tests, vital signs, and physical exams. 
In addition, an independent Data Monitoring Committee (DMC) will review safety and other 
clinical data (with the authority to unblind such data if deemed necessary) on a periodic basis to 
monitor overall subject safety. 
 


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4. 
STUDY ENDPOINTS  
4.1. 
Primary Endpoint 
• Change in the total score of North Star Ambulatory Assessment (NSAA) from 
baseline to Week 52 
4.2. 
Secondary Endpoints 
• Change in 4-stair climb Velocity (4SCV) assessment from baseline to Week 52 
• Change in 10-meter walk/run test from baseline to Week 52 
• Change in TTSTAND from baseline to Week 52 
• Time to Loss of Ambulation (LoA) from baseline to Week 52 
• Proportions of subjects in 10-meter walk/run test at Week 52 
4.3. 
Safety Assessments 
• All treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse 
events (TESAEs), clinically significant laboratory test abnormalities, discontinuation 
of treatment due to treatment-related AEs and hypersensitivity/anaphylactic reactions 
• Number and percentage of subjects with hospitalizations due to any serious adverse 
events (SAEs) with pulmonary and/or cardiac cause(s), after the first dose of 
investigational product (IP) 
• Number and percentage of subjects with bone fractures 
• Annualized height velocity (cm/year) from Baseline to Week 52 
4.4. 
Exploratory Endpoints 
• Change in DVA severity percentage from baseline to Week 52 
• Change in ppFVC and ppPEF assessed by spirometry, from baseline to Week 52  
• Changes in lower extremities vastus lateralis muscle fibrosis score from baseline to 
Week 52, assessed by MRI 
4.5. 
Pharmacokinetics/pharmacodynamics (PK/PD) assessment  
• Population PK/PD analysis  
5. 
GENERAL STATISTICAL CONSIDERATIONS 
5.1. 
General Conventions 
All analyses will be performed using SAS® Version 9.4 or higher. All data collected will be 
presented by data listings for review and substantiation of summary tables. 


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5.1.1. 
Analysis for Categorical Endpoints 
Frequency distributions (number and percentage of subjects) will be presented for categorical 
variables. 
For categorical variables, the confidence interval (CI) of proportions for each treatment group 
will be calculated using the Clopper-Pearson method as appropriate. The SAS PROC FREQ 
procedure with BINOMIAL (EXACT) statement will be used to provide the Clopper-Pearson 
exact 95% CIs for proportions. Bar graphs of proportions for categorical variables will be plotted 
as appropriate. 
5.1.2. 
Analysis for Continuous Endpoints 
For continuous variables, descriptive statistics, including n, mean, standard deviation (SD), 
median, minimum, and maximum, will be presented. Unless otherwise stated, all confidence 
intervals will be two-sided 95% confidence intervals.  
For select continuous variables, line graphs of group mean (and standard error [SE]) and mean 
change from baseline (and SE) values will be plotted over visits. 
Baseline characteristics, safety, efficacy, and other data will be summarized by treatment arm 
based on available data in the Intent-to-Treat (ITT)/Safety Analysis Set, except for the variables 
specifically indicated otherwise. Baseline tables will include an Overall group and inter-quartiles 
(Q1, Q3) for descriptive statistics. 
Efficacy and safety analyses for treatment comparisons will be based on data observed during the 
main study period (52 weeks). Data from the OLE period will be summarized descriptively. 
The statistical comparisons will be performed between treatment groups as deemed appropriate. 
The treatment groups will be presented as follows: 
• Pamrevlumab 
• Placebo 
5.2. 
Analysis Sets 
The following analysis sets will be used for statistical analysis: 
5.2.1. 
Intent-to-Treat Set (ITT)  
The ITT set will include all randomized subjects. Subjects will be analyzed according to their 
randomized treatment arm. 
5.2.2. 
Per-Protocol Set (PPS) 
The per-protocol set will be defined as all randomized subjects who completed at least 24 doses 
of treatment, with baseline and at least one post-baseline NSAA assessments, did not early 
terminated from treatment or study, and no major protocol deviation(s) that significantly impact 
efficacy analyses. 


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5.2.3. 
Safety Analysis Set (SAF) 
The safety analysis set will include all subjects who receive any dose of study medication. All 
safety data will be analyzed using the SAF. Subjects will be analyzed according to the treatment 
actually received. 
5.2.4. 
Immunogenicity Analysis Set (IGS) 
The Immunogenicity Analysis Set (IGS) contains all the Anti-Drug Antibody and/or 
Neutralizing Antibody (ADA/NAb) evaluable patients, who are in the SAF analysis set with at 
least one ADA/NAb sample (with reportable results) taken pre-treatment (i.e., a baseline sample) 
and at least one ADA/NAb sample (with reportable result) taken post-treatment in the OLE 
period.  
5.3. 
General Data Handling Rules and Presentation Specifications 
The following general guidelines will apply to all statistical analyses and data presentations: 
5.3.1. 
Analysis Period 
5.3.1.1. 
On-Study Period 
Unless otherwise specified, the efficacy analysis will be based on the on-study period, which is 
defined as from randomization to the day of last efficacy assessment for main study period prior 
to first study drug infusion in the OLE period for subjects who enrolled in the OLE period; or 
from randomization to the last day of any efficacy assessment for subjects who did not enroll in 
the OLE period. 
For the safety analysis, all safety assessments beyond 60 days of last dose will be excluded from 
summary tables or figures. 
5.3.1.2. 
On-Treatment Period 
The on-treatment analysis includes only the assessments that are observed during On-Study 
Period as defined above (Section 5.3.1.1), or within 4 weeks after last study drug infusion in the 
main study period. On-treatment analysis as one of the sensitivity analyses will only be 
conducted for the primary efficacy endpoint. 
5.3.2. 
Baseline and Change from Baseline Definitions 
Baseline is defined as the last available value obtained prior to the first dose of study drug (or 
randomization date if no infusion received) if not specified otherwise (Section 5.5). The 
acceptable value on Day 1 will be used to define the baseline values. Unscheduled visits prior to 
the first dose will be considered for baseline. 
Change from baseline will be calculated by subtracting the baseline value from the post-dose 
assessment for each subject. 
5.3.3. 
Study Day Calculation  
The day when a subject receives the first dose of study drug after randomization will be 
considered as Day 1 for all analysis. 


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Study day of an assessment/procedure is calculated as follows. 
• For events on or after first dose:  
Study day = Event date – Day 1 date + 1. 
• For events earlier than first dose: 
Study day = Event date – Day 1 date. 
Note: Day 1 date will be the first dose date if the subject receives study treatment. Otherwise, it 
will be the randomization date if the subject does not receive the study treatment after 
randomization. 
5.3.4. 
General Instructions on TFLs 
• For continuous variables that are recorded as “<X” or “>X”, the value of “X” will be 
used in the calculation of summary statistics. 
• All percentages will be rounded to one decimal place. The percentage will be 
suppressed when the count is zero. All durations of time will have 1 decimal place. 
• All tables and listings will have a header showing “FibroGen, Inc.”, protocol number 
(study nickname), date of data cutoff, and Page x of y. A footer will show the 
program file path/name, date of data extraction, run date and run time. 
• More details are available in Appendix 5.  
5.3.5. 
Handling Dropouts and Missing Data 
All assessments collected will be considered for analyses regardless of whether such data are 
collected during treatment or after a subject discontinued treatment. All analyses assume the 
missing data are missing at random (MAR) unless stated otherwise. Detailed missing data 
handling are described in the analysis of specific endpoints. 
5.4. 
Interim Analysis and Data Monitoring Committee 
In addition to routine safety monitoring, an independent DMC is established to review safety 
data on an ongoing basis. A DMC charter will establish the procedures, meeting frequency, and 
scope of responsibilities of the committee.  
This study has no planned or pre-specified interim analysis for either efficacy or futility.  
 
5.5. 
Analysis Visit Windows 
In accordance with Food and Drug Administration (FDA)/ European Medicines Agency (EMA) 
Guidance: During the COVID-19 pandemic, the visit modality (e.g.: in-person versus remotely) 
and scheduling maybe adjusted and conducted at the discretion of the Investigator, in accordance 
with the site’s rules and recommendations, and using all necessary precautions. If a visit must be 
done remotely, it can be conducted with any technology available to the site and study subjects, 
such as via tele-health visits, phone calls, etc. 


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Analysis visits, instead of the nominal visits from case report form (CRF), derived from visit 
dates and visit time windows will be used in the by-visit analyses. Unscheduled visits within a 
visit window (defined in Appendix 2 ) will be grouped into the closest scheduled visits based on 
the visit date. For subjects who have more than one measurement at a certain analysis visit, the 
last measurement will be used, with the following exceptions:  
• Liver function tests, such as Alanine Aminotransferase (ALT), Aspartate 
Aminotransferase (AST), Gamma-Glutamyl transferase (GGT), Alkaline Phosphatase 
(ALP), and total bilirubin, in which the maximum value will be used. 
• Vital signs: the values on the infusion days will be used if applicable. 
• Spirometry data: the Best Test Read (BTR) values will be used for analysis.  
Efficacy parameters will be summarized by analysis visit defined by the following assessment 
windows (Appendix 2). The date of the first dose will be considered as the date of Day 1 for all 
analyses. Subjects will receive study drug every 2 weeks. The visit window for these visits is ±3 
days. Duchenne Video Assessment can be performed in the subject’s home up to 14 days prior to 
the scheduled study visit. 
6. 
STATISTICAL ANALYSES 
6.1. 
Subject Enrollment and Disposition 
6.1.1. 
Eligibility 
Eligibility will be summarized for all screened subjects. The data will be summarized with 
respect to: 
• number of subjects screened 
• number (%) of subjects screen-failed 
• number (%) of subjects for each failed inclusion/exclusion criterion 
Subject level inclusion criteria not met/exclusion criteria met listings will be provided. 
6.1.2. 
Subject Accountability and Disposition 
The number (%) of subjects randomized (ITT), dosed (SAF), Per-Protocol Set (PPS), completed 
the main study, entered the OLE period, and discontinued prematurely from treatment and study 
in the main study and OLE respectively will be presented for each treatment group and for all 
subjects pooled. 
Reasons for premature discontinuation of treatment in the main study will be summarized by 
treatment group for the ITT population. A listing for the subjects who discontinue treatment 
prematurely in the main study will be presented. 
6.2. 
Important Protocol Deviations 
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• Entry Deviation: Subjects who entered the study, but did not meet inclusion/exclusion 
criteria 
• Withdrawal Deviation: Subject met withdrawal criteria during the study but was not 
withdrawn. 
• Dosing Deviation: Subject received the wrong treatment or incorrect dose; including 
incorrect timing of a dose; or subjects who missed more than 10% doses of prescribed 
study medication during the overall treatment period. 
• Prohibited Medication Deviation: Subject received disallowed concomitant 
medications or non-drug therapy. 
All above protocol deviations will go through the medical review process. 
A subset of pre-specified important protocol deviations will be defined as major protocol 
deviations and subjects with major protocol deviations will be excluded from PPS analysis. 
The number and percentage of subjects with important protocol deviations will be categorized 
and tabulated as appropriate for the ITT population. COVID-19 related important protocol 
deviations will be summarized separately. All protocol deviations will be finalized prior to 
database lock and unblinding. 
6.3. 
Demographics and Baseline Characteristics   
Demographics and baseline characteristics will be summarized descriptively for subjects in ITT 
and SAF. Each parameter will be presented in data listings. 
Baseline values for efficacy assessments will be presented in baseline tables as appropriate. 
6.3.1. 
Demographics and Baseline Characteristics 
Demographic parameters and other important baseline and disease characteristics will be 
summarized by treatment group. These include but may not be limited to age, ethnicity, race, 
weight, body-mass index (BMI), and body surface area (BSA), total score of NSAA. 
Computation formula: 
BSA = [Weight 0.425 (kg) * Height 0.725 (cm)] x 0.007184 
Age = Year of informed consent date – Year of birth 
Descriptive statistics (n, mean, standard deviation, median, interquartile (Q1, Q3), range 
(=minimum, maximum) will be presented for continuous variables.  Frequency distributions 
(number and percentage of subjects) will be presented for categorical variables. 
6.3.2. 
Baseline DMD Disease Characteristics 
Baseline DMD disease characteristics include: 
1. Age in years when DMD was diagnosed = Year of date of diagnosis - Year of birth 
2. Age when subject initiated ventilation = Year of date when subject initiated ventilation - 
Year of birth 


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3. Years since subject initiated ventilation = Current age – Age when subject initiated 
ventilation 
4. Corticosteroids use: yes or no. If yes, age when subject began corticosteroids (= Year of 
date of subject began corticosteroids - Year of birth), and years since subject began 
corticosteroids (= Current age – Age when subject began corticosteroids). 
5. Spine surgery: yes or no. If yes, age when spine surgery (=Year of Date of subject began 
spine surgery - Year of birth) was done, and years since the most recent spine surgery (= 
YRDIF (Date of spine surgery, Day 1 Visit Date, ‘Actual’))  
6. Is exon 44 deleted? – yes or no 
Additionally, the following baseline disease characteristics, but are not limited to, will be 
summarized. 
7. Bone parameters 
• Bone fractures (Refer to Section 6.8.7 ) 
• Scoliosis  
• Osteoporosis 
8. Joint contractures  
9. Cardiac parameters 
• Cardiomyopathy  
10. Respiratory parameters 
• Ventilation support  
• Number of years since ventilation support initiated 
• Sleep apnea  
• ppFVC  
11. Metabolic parameters 
• Insulin resistance 
• Obesity  
• Vit D deficiency 
• Delayed puberty 
12. Corticosteroids (CS) use  
• Age at CS initiation 
• Prednisone/Prednisolone  
• Deflazacort  
• Regimen 


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− Daily 
− Other 
Other symptoms such as headaches, attention deficit hyperactivity disorder (ADHD), and autism 
spectrum disorder will also be summarized. 
6.3.3. 
Medical History 
Medical History of interest including allergies and surgeries, coded in system organ class (SOC) 
and preferred term (PT) using MedDRA (version 25.0 or higher), will be summarized for the ITT 
Analysis Set.  Subject medical history listings will be provided.  
6.4. 
Prior and Concomitant Medications 
The World Health Organization Drug Dictionary (WHODD) Version (WHO Drug March 1, 
2020, or later version) will be used to classify prior and concomitant medications by therapeutic 
class and generic name based on Anatomical Therapeutic Chemical (ATC) code level 3.   
Prior medication is defined as any medication taken and stopped prior to the first infusion of the 
study medication.  Concomitant medication is defined as any medication used concomitantly 
with the study drug that were not stopped before the first infusion or used concomitantly after the 
first infusion, ending 60 days after the last treatment. Partially or incomplete missing 
prior/concomitant medication start or stop date will be imputed (Appendix 1). 
Both prior and concomitant medication usage will be summarized by the number (%) of subjects 
receiving the drug within each therapeutic class and ATC code level 3 and preferred term for the 
SAF. Multiple usage of the same drug by a patient will be counted only once. 
In addition, a listing of all medications (prior or concomitant) taken during the course of the 
study (from screening through the end of study) captured in Concomitant Medication CRF, as 
well as Non-Drug Therapies CRF will be provided. Separate reports are provided for the main 
and OLE studies respectively. 
Data on concomitant DMD medications administered during the study are collected and analyzed 
accordingly. Summary of concomitant DMD medications such as types of corticosteroids and 
duration of corticosteroid will be provided. 
To evaluate the use of co-administered medications that are narrow therapeutic CYP substrates, 
the clinical database of concomitant medication will be searched for presence of narrow 
therapeutic index cytochrome P450 substrates and summarized. The list of related medications 
will be finalized before database lock. 
6.5. 
Study Drug Exposure and Treatment Compliance 
6.5.1. 
Study Drug Exposure 
The number and percentage of subjects who receive study medication will be summarized by 
treatment group for the SAF.   
Duration of weekly exposure/treatment is calculated as:  
Weeks in treatment = (last dose date - first dose date + 1)/7 (keep 1 decimal place). 


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Duration of weekly exposure will be tabulated by treatment group for the SAF analysis set.  
The number of infusions and average infusion dose amount in mg and mg/kg, any interruption 
during infusion (Y/N), and reason for missed dose or interruption will be summarized for the 
SAF analysis set. 
6.5.2. 
Treatment Compliance 
Dosing for pamrevlumab (or placebo) will be based on subject’s body weight, which will be 
measured at Screening and every 12 weeks thereafter to determine dose for the subsequent 
12-week interval. The total dose of pamrevlumab (or placebo) is not to exceed 4.1g per infusion 
or to align with the protocol. Subjects weighing more than 117 kg will receive the maximum 
allowable dose of 4.1g.  
Compliance will be calculated as total amount of dosage (mg) the subject received divided by the 
total amount of dosage (mg) the subject is scheduled to receive during the participation in 
treatment.  
𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 (%) =
actual total dosage received (mg)
total planned dosage (mg) while actively in treatment × 100 
Descriptive statistics for study medication compliance will be presented by treatment group for 
the SAF. Treatment compliance will be summarized as a continuous variable and as a categorical 
variable (<70%, 70% –<80%, 80% –<90%, and 90% - 100%, >100%). 
6.6. 
Efficacy Analyses 
The primary and secondary endpoints will be tested using a fixed sequence procedure to preserve 
the study-wide error rate of 5%. Under the sequential analysis, the primary and secondary 
efficacy endpoints will be tested in a predefined sequence according to the order listed in Table 1 
each at the usual alpha= 0.05 level of statistical significance. The testing will cease when a 
failure occurs in the pre-determined sequential hypothesis testing and all p-values for the 
subsequent testing will be considered nominal.  
All analyses for efficacy endpoints will be performed for the ITT analysis set during the 
On-Study period (Section 5.3.1.1), unless noted otherwise. 


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Table 1: 
Testing Sequence of Primary and Secondary Endpoints  
Testing Sequence 
Endpoint 
1 (primary endpoint) Change in the total score of North Star Ambulatory Assessment (NSAA) from 
baseline to Week 52 
2 
Change in 4-stair climb Velocity (4SCV) assessment from baseline to Week 52 
3 
Change in the 10-meter walk/run test from baseline to Week 52 
4 
Changes in Time to Stand (TTSTAND) from baseline to Week 52 
5 
Time to Loss of Ambulation (LoA) from baseline to Week 52 
6 
Proportions of subjects in 10-meter walk/run test at Week 52 
6.6.1. 
Primary Endpoint Estimand and Analysis  
The primary efficacy endpoint in this study is defined as Change from Baseline in the total score 
of NSAA at Week 52. 
The NSAA consists of 17 activities, each scored as 0, 1, or 2. The sum of these 17 scores will be 
used to form a total score. If fewer than 15 of the 17 activities are performed, the total score with 
be considered missing. If from 15 to 16 activities are performed, the total score will be calculated 
by multiplying the sum of the scores in the x activities that were performed by 17/x. If an activity 
cannot be performed due to disease progression or loss of ambulation, a score of zero will be 
assigned. 
The primary efficacy endpoint will be analyzed using ITT as the primary analysis set. 
The hypothesis to be tested for the primary efficacy analysis is: 
H0: Change from Baseline in the total score of NSAA at Week 52 for the pamrevlumab 
arm = Change from Baseline in the total score of NSAA at Week 52 for the placebo 
group 
Versus: 
H1: Change from Baseline in the total score of NSAA at Week 52 for the pamrevlumab 
arm ≠ Change from Baseline in the total score of NSAA at Week 52 for the placebo 
group 
H0 will be tested at the two-sided alpha = 0.05 level of significance and will be rejected if the p < 
0.05 from the test. 
6.6.1.1. 
Primary Analysis Using Mixed Model for Repeated Measure (MMRM) 
6.6.1.1.1. Estimand Strategy  
The primary estimand is intended to provide a population level estimate of the treatment effect of 
the pamrevlumab on a continuous endpoint, regardless of participant compliance with the IP 
dosing. Treatment policy strategy will be implemented, which means all observed measurements 
after randomization will be used in the primary analysis. 


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6.6.1.1.2. Population of Interest 
The ITT population includes all randomized subjects during the on-study period as defined in 
Section 5.3.1.1.  
6.6.1.1.3. Intercurrent Event Handling  
Treatment discontinuation (such as due to adverse event, lost to follow-up, withdrawal by 
subject, physician decision, protocol deviations, etc.): Missing data will be implicitly imputed 
under missing at random assumption. 
Death: The worst postbaseline score of all patients in the ITT population would be used to 
impute all missing values due to death. Missing study day will be imputed as target day of the 
corresponding analysis visit. 
6.6.1.1.4. Analysis Variable 
Change from baseline in the total score of NSAA in the main study period, including scheduled, 
unscheduled, and available assessments after treatment discontinuation, up to the targeted week 
52 during the On-Study period (Section 5.3.1.1), will be included in the analysis. 
6.6.1.1.5. Population Summary for Treatment Comparison  
Treatment difference of Least-square mean (LSMean) and SE at week 52 and corresponding 
95% CI will be presented. 
The change in the total score of NSAA, from baseline to Week 52 will be analyzed using a 
Mixed Model for Repeated Measure (MMRM) with treatment, visit, visit-by-treatment 
interaction, baseline total score of NSAA, age, and corticosteroids use at baseline with 
appropriate covariance matrix (see section below) for the within subject covariance over time.  
Covariance Structure Strategy 
The unstructured covariance structure for the within-patient errors in the model will be applied 
first. The by-treatment-group option is included to the covariance pattern to improve the model 
efficiency. 
If the algorithm for unstructured covariance pattern does not converge, the following covariance 
structures will be tested in sequence until the model converges: heterogeneous Toeplitz, 
homogeneous Toeplitz, first-order autoregressive, compound symmetry, and variance 
component. The sandwich estimator will be used if there is convergence issue. If the model does 
not converge for all covariance structures listed above, some least significant factors or 
interaction terms (p>0.05) can be excluded from the model to achieve convergence. The revised 
model with fewer factors or interaction terms will be tested using the same sequence as specified 
above.  
 


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6.6.1.2. 
Sensitivity Analyses of the Primary Endpoint 
6.6.1.2.1. MI ANCOVA 
Multiple Imputation Analysis of Covariance model (MI ANCOVA) will be performed to 
evaluate the robustness of the primary analysis as a sensitivity analysis. 
6.6.1.2.1.1. Estimand Strategy 
Same as Section 6.6.1.1.1. 
6.6.1.2.1.2. Population of Interest 
Same as Section 6.6.1.1.2. 
6.6.1.2.1.3. Intercurrent Event Handling 
Under the MAR assumption, subjects who discontinued from the treatment early alive are 
assumed to have the same data pattern as subjects who remain in the study for the same 
treatment arm. Multiple imputation will be carried out to impute missing data for visits up to 
Week 52. 
Death: same as Section 6.6.1.1.3. 
6.6.1.2.1.4. Analysis Variable 
Same as Section 6.6.1.1.4 (Missing value imputation rules are defined below). 
6.6.1.2.1.5. Population Summary for Treatment Comparison  
The combined treatment difference of LSMeans (and SE) and the corresponding 95% CI for the 
estimated change from baseline in total score of NSAA at Week 52 will be presented. 
Analysis will be performed in 3 steps. 
Step 1 - First, the intermittent missing NSAA data will be imputed for each treatment relying on 
non-missing data from all subjects within each treatment group using the Markov Chain Monte 
Carlo (MCMC) imputation model with baseline NSAA, and the available non-missing NSAA to 
generate a monotone missing data pattern that only has missing data at end for planned visits 
through Week 52. The reported (observed) value will be used for multiple imputation. Change 
from baseline values will be derived using the difference between the imputed or observed post-
baseline values and baseline values. 
Then, for each dataset above, missing data will be imputed to derive 200 imputed datasets with non-
missing data. 
Step 2 - The 200 multiple-imputation datasets with imputed and observed NSAA data at Week 
52 will be analyzed separately for each imputation using the ANCOVA method. The ANCOVA 
model will contain terms for treatment, baseline NSAA measurements, covariates. The 
ANCOVA model will include the same covariates as in the primary analysis. The LSMean and 
corresponding SE for the change from baseline in total score of NSAA at Week 52 will be 
estimated. 


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Step 3 - The SAS PROC MIANALYZE will be used to derive the final estimates and test 
statistics summarizing the 200 analysis results. 
6.6.1.2.2. Pattern Mixture Models under MNAR for Missing Data: Jump-to-Control 
Analysis  
The goal of the following analyses is to address the possibility of data being missing not at 
random (MNAR).  
6.6.1.2.2.1. Estimand Strategy 
Same as Section 6.6.1.1.1. 
6.6.1.2.2.2. Population of Interest 
Same as Section 6.6.1.1.2. 
6.6.1.2.2.3. Intercurrent Event Handling  
Treatment discontinuation (such as due to AEs, lost to follow-up, withdrawal by subject, 
physician decision, protocol deviations, etc.): The missing data pattern for the pamrevlumab 
subjects after withdrawal from the study can be assumed to switch to the same data pattern as 
subjects on the placebo treatment. Subjects that discontinued from the placebo arm are assumed 
to have the same data pattern as placebo subjects that remain in the study. This is often called the 
jump-to-control approach. 
Death: same as Section 6.6.1.1.3. 
6.6.1.2.2.4. Analysis Variable 
Change from baseline in the total score of NSAA at Week 52 (Missing value imputation rules are 
defined below). 
6.6.1.2.2.5. Population summary for treatment comparison 
Under the jump-to-control assumption, the analysis will be carried out in 3 steps. 
Step 1 - the missing NSAA data will be imputed to derive 200 imputed datasets with non-missing 
data according to the jump-to-control data pattern. 
Step 2 - The 200 multiple imputation datasets with imputed and observed data will be analyzed 
separately using the ANCOVA method separately as described in Section 6.6.1.2.1.5.   
Step 3 - The SAS PROC MIANALYZE will be used to derive the final estimates and test 
statistics summarizing the 200 dataset results. 
The combined treatment difference of LSMeans, corresponding SE and 95% CI for the estimated 
change from baseline in total score of NSAA at week 52 will be presented. 


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6.6.1.2.3. Pattern Mixture Models under MNAR for Missing Data: Delta-Adjusting 
(Tipping Point) Analysis 
6.6.1.2.3.1. Estimand Strategy 
Same as Section 6.6.1.1.1. 
6.6.1.2.3.2. Population of Interest 
Same as Section 6.6.1.1.2. 
6.6.1.2.3.3. Intercurrent Event Handling 
Treatment discontinuation (such as due to AEs, lost to follow-up, withdrawal by subject, 
physician decision, protocol deviations, etc.): An alternative assumption is that the missing data 
for the pamrevlumab treated subjects who discontinue early have a lower expected value than the 
pamrevlumab subjects remaining in the study, while subjects who discontinue from the placebo 
arm are assumed to have the same data pattern as placebo subjects remaining in the study. This is 
often called the delta-adjusting (or tipping point) approach. 
Death: same as Section 6.6.1.1.3. 
6.6.1.2.3.4. Analysis Variable 
Change from baseline in the total score of NSAA assessments at Week 52 (Missing value 
imputation rules are defined below). 
6.6.1.2.3.5. Population summary for treatment comparison 
The integrated treatment difference of LSMeans, corresponding SE and 95% CI for the change 
from baseline in total score of NSAA at week 52 will be presented. 
The multiple imputation analysis will be performed as follows. 
Step 1 - the missing NSAA data will be imputed to derive 200 imputed datasets with non-missing 
data according to the delta-adjusting data approach. 
Step 2- The observed and imputed NSAA data will be analyzed using the ANCOVA method 
separately as described in Section 6.6.1.2.1.5 for each of the 200 imputed datasets. The LSMean 
and corresponding SE for the change from baseline in NSAA at week 52 will be estimated. Same 
as Step 2 in Section 6.6.1.2.1.5. 
Step 3- The SAS PROC MIANALYZE will be used to summarize the final estimates and test 
statistics from the 200 dataset results. Same as Step 3 in Section 6.6.1.2.1.5. 
6.6.1.2.4. On-treatment Analysis for Primary Efficacy Endpoint  
A sensitivity analysis will be performed for NSAA assessed during on-treatment period as 
defined in Section 5.3.1.2. 
6.6.1.2.4.1. Estimand Strategy 
Same as Section 6.6.1.1.1. 


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6.6.1.2.4.2. Population of Interest 
Same as Section 6.6.1.1.2. 
6.6.1.2.4.3. Intercurrent Event Handling 
Same as Section 6.6.1.1.3 
6.6.1.2.4.4. Analysis Variable 
Only on-treatment NSAA assessments will be included in the analysis 
6.6.1.2.4.5. Population Summary for Treatment Comparison  
Same as Section 6.6.1.1.5.  
6.6.1.2.5. Cumulative Loss of Function Analysis for Primary Efficacy Endpoint 
This sensitivity analysis used data representing cumulative failure to perform 17 items of NSAA 
in patients at multiple time points over 52 weeks.  
6.6.1.2.5.1. Estimand Strategy 
Failure to perform an item was defined as a score transition from 2 or 1 to 0 at evaluation. Only 
post-baseline failures were considered in the present analysis. For each treatment group, the 
mean of all such patients' individual curves will be constructed, reflecting the average cumulative 
number of failures over time. The higher the curve, the worse the study treatment effect. To 
quantify the group difference, we assume that the ratio of two corresponding underlying group-
wise curves is constant over time, and use the Lin, Wei, Yang and Ying (LWYY) analytic 
method, which is the same as the Anderson-Gill method with the robust variance estimate, to 
estimate this constant ratio. This summary measure can also be interpreted as the ratio of the 
intensities of occurrences of failures over time.  If this assumption is not plausible, the resulting 
estimate reflects an averaged ratio between the two curves over time. The lower the ratio, the 
greater the treatment effect.  
6.6.1.2.5.2. Population of Interest 
ITT as defined in Section 5.2.1. 
6.6.1.2.5.3. Intercurrent Event Handling Strategy 
If a patient discontinued, the cumulative failure number was censored upon discontinuation. 
6.6.1.2.5.4. Analysis Variable 
Cumulative counts of failure to perform 17 items of NSAA. 
6.6.1.2.5.5. Population Summary for Treatment Comparison  
All post-baseline visits during the double-blind period will be included in the analysis. 
Cumulative counts of failure to perform 17 items of NSAA at post-baseline visits will be 
analyzed using the Anderson-Gill method with the model-based covariance estimate to estimate 


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the ratio between treatment arms. Rate ratio between 2 arms including 95% CI and p-value will 
be reported. Sample SAS code is provided below. 
proc phreg data=final covs(aggregate); 
   model (TStart, TStop) * Status(1) = Trt Number; 
   id id; 
   where TStart < TStop; 
run; 
Note: 1= censored. For more information, please refer to SAS online help. 
6.6.2. 
Secondary Endpoints Estimands and Analyses  
The secondary endpoints during the on-study period (as defined in Section 5.3.1.1) will be 
analyzed in the order specified in Table 1.  
6.6.2.1. 
Secondary Endpoints using MMRM Model 
6.6.2.1.1. Estimand Strategy 
Same as Section 6.6.1.1.1. 
6.6.2.1.2. Population of Interest 
Same as Section 6.6.1.1.2. 
6.6.2.1.3. Intercurrent Event Handling  
Same as Section 6.6.1.1.3. 
6.6.2.1.4. Analysis Variables 
6.6.2.1.4.1. Change in 4-Stair Climb Velocity (4SCV) assessment from baseline to Week 52 
4SCV is calculated as the ratio of the number of stairs climbed divided by the number of seconds 
taken to complete the 4-stair climb. The result is converted into velocity (distance/time). 
6.6.2.1.4.2. Change in the 10-Meter Walk/Run test from baseline to Week 52 
The time required for a participant to run or walk a distance of 10 meters as quickly as possible 
is calculated as velocity (distance/time). 
6.6.2.1.4.3. Changes in Time to Stand (TTSTAND) from baseline to Week 52 
The time required for a participant to stand from supine position. A longer time reflects a worse 
outcome. A negative change from baseline indicates an improvement. 
6.6.2.1.5. Population Summary for Treatment Comparison  
Same as Section 6.6.1.1.5. 


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6.6.2.2. 
Time-to-Event Secondary Endpoints 
6.6.2.2.1. Estimand Strategy 
The secondary estimands are intended to provide a population level estimate of the treatment 
effect of the pamrevlumab on time-to-event endpoints, regardless of participant compliance with 
the IP dosing. 
6.6.2.2.2. Population of Interest 
Same as Section 6.6.1.1.2. 
6.6.2.2.3. Intercurrent Event Handling  
Treatment discontinuation (such as early termination due to AEs, Lost to Follow-Up, Withdrawal 
by Subject, Physician Decision, Protocol Deviations, etc.): treatment policy strategy will be 
employed, which means all observed data will be used regardless of treatment discontinuation. 
Death: same as Section 6.6.1.1.3. 
6.6.2.2.4. Analysis Variables 
Time (Days) to Loss of Ambulation (LoA) is defined as the number of days from randomization 
to the date of loss of ambulation, or all-cause death based on observed data, whichever occurs 
earlier during the on-study period as described in Section 5.3.1.1. 
Subjects without an event will be censored on the date of the last Muscle Function Tests (MFTs) 
assessment within 357 days after randomization, but prior to the first study drug infusion in the 
OLE period (for subjects who enrolled in the OLE period). Alive subjects who do not have any 
post-baseline MFT assessments will be censored on Day 1. Subjects who died after Week 10, but 
do not have any post-baseline MFT assessments will be censored on Day 1 as well. However, 
subjects who died within 10 weeks will be considered as an event. 
6.6.2.2.5. Population summary for treatment comparison 
The hazard ratio, corresponding SE, and 95% CI for the hazard ratio will be presented. 
The Cox proportional hazard model by treatment will be used to estimate the hazard ratio and its 
corresponding 95% CI. A log-rank test by will be used for treatment comparison. 
The number of subjects with Time to LoA will be summarized descriptively using the Kaplan-
Meier method. 
6.6.2.3. 
Proportions of subjects in 10-meter walk/run test at Week 52 
6.6.2.3.1. Estimand Strategy 
The estimand is to estimate the treatment effect of the pamrevlumab by comparing the 
proportions of subjects having results >10 seconds in 10-meter walk/run test at Week 52, 
regardless of participant compliance with the IP dosing. 


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6.6.2.3.2. Population of Interest 
Same as Section 6.6.1.1.2. 
6.6.2.3.3. Intercurrent Event Handling  
Treatment discontinuation (such as early termination due to AEs, Lost to Follow-Up, Withdrawal 
by Subject, Physician Decision, Protocol Deviations, etc.): treatment policy strategy will be 
employed, which means all observed data will be used regardless of treatment discontinuation. 
Death: same as Section 6.6.1.1.3. 
6.6.2.3.4. Analysis Variables 
Proportions of subjects having results in 10-meter walk/run test at Week 52. 
6.6.2.3.5. Population summary for treatment comparison 
The proportions of subjects having results >10 seconds or <=10 seconds in 10-meter walk/run 
test at Week 52 will be summarized and presented. Fisher’s exact test will be used for treatment 
comparison of proportions of subjects having results >10 seconds. Two-sided P-value at 
significance level of 0.05 from Fisher’s exact test is presented. 
6.6.3. 
Exploratory Endpoint Analyses 
6.6.3.1. 
Change in Duchenne Video Assessment severity percentage from baseline to 
Week 52 
The DVA tool provides a standardized way to document and assess patient quality of movement. 
Caregivers will video record subjects doing specific movement tasks at home using a secure 
mobile application within 2 weeks prior to the clinic visits specified in the Schedule of 
Assessments. Trained physical therapists will score the videos in a secure scoring dashboard 
using scorecards with pre-specified compensatory movement criteria. Casimir, the organization 
that developed the DVA, will manage DVA data collection, quality, and scoring. 
Summary of the listings and analyses Duchenne Video Assessment severity percentage and 
Clinical Global Impression of Change (CGI-C) scores will be based on the ITT population.  
Details of DVA data analysis can be found in a separate document named “Duchenne Video 
Assessment Statistical Analysis Plan”.  
6.6.3.2. 
Change in ppFVC and ppPEF from Baseline to Week 52 
Exploratory endpoints, the change from baseline to Week 52 in ppFVC and ppPEF will be 
analyzed using the same intercurrent handling and analysis method as for the primary endpoint. 
6.6.3.3. 
Change in lower extremities vastus lateralis muscle fibrosis score from baseline 
to Week 52, assessed by MRI 
Exploratory endpoint, the change from baseline at week 52 in fibrosis score of lower extremities, 
vastus lateralis muscle will be analyzed using an ANCOVA model, which contains terms for 
treatment, baseline measurements.  


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6.6.4. 
Subgroup Analyses of the Specified Endpoints 
The subgroups may include but are not limited to:  
• Age group (<= 9 years, > 9 years) 
• Race (White, Other) 
• Baseline total score of NSAA (<= median, > median) 
• Corticosteroids use (Deflazacort, Prednisone/Prednisolone) 
• Time to rise from the floor subgroup (<= 5, > 5 seconds) 
• Baseline 10-meter walk/run Test subgroup (<= 5, > 5 seconds) 
• ADA status (Positive, Negative) 
• Regional subgroups: 
o US, Non-US 
o China, Non-China  
The primary endpoint NSAA will be repeated for relevant and appropriate subgroups. Secondary 
endpoints 4SCV, 10-meter walk/run test, and TTSTAND will also be analyzed by subgroups. 
The LSMean of treatment difference and corresponding 95% CI will be presented in a forest plot 
as appropriate. 
If the subjects who took the prohibited medications constitute to more than 10% of the 
population, then the subgroup analysis – with or without prohibited medications will be 
performed. 
6.7. 
PK Analyses 
A summary of drug concentrations by visit as well as a listing will be provided. A population PK 
analysis, as well as an exposure-response analysis, will be defined in a separate PK analysis plan.  
6.8. 
Safety Analyses 
6.8.1. 
Adverse Events 
Adverse events will be coded using MedDRA version 25.0 or higher. 
A new or worsening AE occurring on or after the first dose of study medication and within 60 
days after the last dose of study drug is defined as a TEAE. Partially or incomplete missing AE 
start/stop date/time will be imputed (Appendix 1). 
If more than one event occurs with the same SOC and PT for the same patient, the patient will be 
counted only once for that preferred term using the most severe and most related occurrence for 
the summarization by common terminology criteria for adverse events (CTCAE) severity grade 
and by relationship to the study medication. Relationship to study drug will be imputed as 
“Related” for any TEAE with missing value for relationship.  
The following summary AE tables including number (%) of subjects will be produced: 


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• Summary of all TEAEs 
• TEAEs by PT 
• TEAEs by SOC and PT 
• TEAEs by SOC, PT, and maximum severity 
• TEAEs with severity grade ≥3 by SOC and PT 
• TEAEs related to study medication determined by investigator by SOC and PT 
• Common TEAEs (≥ 5% of subjects in either treatment arm) by SOC and PT 
• Common non-serious TEAEs (≥ 5% of subjects in either treatment arm) by SOC and 
PT (Note: this is required for ClinicalTrials.gov) 
• TEAEs leading to discontinuation of study medication by SOC and PT 
• TEAEs leading to interruption of study medication by SOC and PT 
• Treatment-emergent serious AEs (TESAEs) by SOC and PT 
• TESAEs by SOC, PT, and maximum severity 
• TESAEs related to study medication determined by investigator by SOC and PT 
• Fatal TESAEs (i.e., adverse events that has an outcome of death) by SOC and PT 
• All cause deaths 
Listings of serious adverse events (SAEs), adverse events leading to study drug discontinuation, 
hypersensitivity, and infusion reactions, and all cause deaths will be provided. 
Additionally, the following safety analyses will be conducted: 
• Number and percentage subjects with bone fractures (Refer to Section 6.8.7) 
• Number and percentage of subjects with hospitalizations due to any serious adverse 
events with pulmonary and/or cardiac cause(s), after the first dose of investigational 
product (IP) 
Refer to Section 6.8.6 for special safety events such as hypersensitivity reactions and related 
topics. 
6.8.2. 
Clinical Laboratory Assessments 
Blood samples are drawn for the following analyses showed in Table 2 .  
Table 2: 
Laboratory Tests 
CBC:  
Chemistry Panel:  
Absolute neutrophil count (ANC)  
BUN  
Eosinophils  
Creatine Kinase  
RBCs (Erythrocyte count)  
Creatinine  
Hematocrit %  
Chloride  
Hemoglobin  
Magnesium  
WBCs (Leukocyte count)  
ALP  


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Lymphocytes  
ALT  
Monocytes  
AST  
Neutrophils  
Bilirubin, total  
Platelets  
Albumin  
CRP  
Phosphorous  
Basophils  
Potassium  
 
Sodium  
 
GGT  
 
Calcium  
 
GFR 
 
Cystatin-C 
Laboratory test results and change from baseline are summarized by analysis visit and by 
treatment arm.  
CTCAE grade 3 or higher lab test results will be considered potentially clinically significant 
(Appendix 4 ). These results are summarized and presented in a data listing. 
Shift tables to summarize changes from baseline to each visit in CTCAE v5.0 categories are 
tabulated. Shift from baseline to most severe CTCAE category during the study is also 
summarized.  
Due to central lab kit shortages caused by Covid-19, lab data may be collected using local labs in 
lieu of the central lab. The local lab data will be integrated with central lab data, when 
appropriate and feasible. Sensitivity analyses may be performed for key analyses of lab 
parameters with and without local lab values (i.e., set to missing). 
An eDISH (evaluation of Drug Induce Severe Hepatotoxicity) analytical graph, which is a scatter 
plot of maximum observed total bilirubin versus maximum observed ALT or AST, will be 
generated to identify cases in Hy’s law range.  
6.8.3. 
Vital Signs 
Pulse (beats/min), diastolic and systolic blood pressure (mmHg), respiration (breaths/min), and 
temperature (°C) will be descriptively summarized by treatment at selected visits.  
Vital sign values are potentially clinically significant (PCS) if they meet both the observed value 
criteria and the change from baseline criteria listed in Table 3 below. The number and percentage 
of subjects with post-baseline PCS values will be tabulated by treatment group. The percentages 
are to be calculated relative to the number of subjects with baseline and at least one post-baseline 
assessment.  The numerator is the total number of subjects with at least one post-baseline PCS 
vital sign value. A supportive listing of subjects with post-baseline PCS values will be provided 
including the treatment, subject ID, study center ID, baseline, and post-baseline values.  A listing 
of all AEs for subjects with PCS vital signs will also be provided. 


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Table 3: 
Criteria for Potentially Clinically Significant Vital Signs 
Vital Sign Parameter 
Flag 
Criteria* 
Observed Value 
Change from Baseline 
Systolic Blood Pressure (mmHg) 
High 
≥170 
Increase of ≥ 20 
Low 
≤90 
Decrease of ≥ 20 
Diastolic Blood Pressure (mmHg) 
High 
≥110 
Increase of ≥15 
Low 
≤45 
Decrease of ≥ 15 
Pulse Rate (bpm) 
High 
≥120 
Increase of ≥20 
Low 
≤50 
Decrease of ≥ 20 
Weight (kg) 
High 
- 
Increase of ≥20% 
Low 
- 
Decrease of ≥ 20% 
* Except for body weight, a post-baseline value is considered as a PCS value if it meets both criteria for observed 
change from baseline. 
6.8.4. 
Physical Examination 
Clinically significant changes in PE results from baseline will be summarized by treatment over 
visit. A shift table will be provided if appropriate. A listing of clinically significant changes in 
PE results from baseline will be provided. 
6.8.5. 
Electrocardiogram 
ECG results will be provided in a listing only. 
6.8.6. 
Special Safety Events  
Treatment-emergent special safety events including:  
1. Hypersensitivity (any time)  
2. Infusion reactions (on day of infusion or 1 day post any study drug infusion) 
3. Anaphylactic reactions (on day of infusion or 1 day post any study drug infusion) 
Items 1 and 2 include both hypersensitivity and angioedema events. Both items will be listed and 
summarized similarly to TEAEs:   
• Events by event type, SOC, PT, and maximum severity, 
• Events by event type, SOC, PT. 
Items 3 uses a modified SMQ to retrieve events under anaphylactic reactions and will be listed 
and summarized by treatment and PT only.   
The preferred term list for these special safety events will be finalized prior to database lock. 
6.8.7. 
Bone Fractures 
Bone fractures are summarized, but not limited to, by types of bone fractures, namely, long bone 
fractures and vertebral compression fractures.  
 
Long bones fractures: 


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• Lower extremities: femur (thigh); tibia; fibula (leg), metatarsus, phalanges (foot). 
Joint fractures: hip, knee, ankle; 
• Upper extremities: humerus (arm); radius; ulna (forearm); metacarpus, phalanges 
(hand, palm); Joint fractures: shoulder, elbow, wrist. 
 
Vertebral compression fractures: 
Spine compression fracture, vertebral compression fracture, spine fracture, or vertebral 
fracture indicate the same type of vertebral compression fractures. The level of 
compression fracture is indicated by vertebrae: C1–C7 (cervical spine); T1–T12 (thoracic 
spine); L1–L5 (lumbar spine); S1-S5 (sacrum, fused), coccyx (3-5, fused). 
Other:  
Hip bone fracture; foot fracture (other than long bones); hand fracture (other than long 
bones); other. 
6.8.8. 
Subgroup Analyses of Safety Endpoints 
The subgroup analysis will be conducted for the safety endpoints of TEAEs and TESAEs. The 
subgroups are specified in Section 6.6.4 , including age, race, corticosteroids use, regional 
subgroups and ADA status. 
6.9. 
Biomarker Endpoint Analysis 
A sample for Tryptase at time of immunogenic reaction will be collected.  A listing will be 
provided for the data. 
6.10. 
Immunogenicity Analysis 
Analysis of immunogenicity data will be based on IGS.  Analysis dataset and data listing will 
include all available Human Anti-Human Antibody (HAHA, ADA) samples. The following 
terms and definitions are implemented. 
6.10.1. 
Terms and Definitions 
6.10.1.1. Sample ADA Status: 
• Baseline ADA-positive sample: ADA is detected in the last sample before initiation 
of treatment. 
• Baseline ADA-negative sample: ADA is not detected in the last sample before 
initiation of treatment. 
• Treatment-emergent ADA-Positive: Meets definition of treatment-induced or 
treatment-boosted ADA. After initiation of treatment,  
− Treatment-induced ADA-Positive: a post-treatment positive ADA is detected in 
a subject for whom pre-treatment ADA assessment is either negative or not 
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− Treatment-boosted ADA-Positive: pre-existing ADA were boosted to a higher-
level following study treatment, i.e. pre-treatment positive ADA titer was boosted 
by at least 2 dilution steps (4-fold) following study treatment. 
• ADA-negative sample: After initiation of treatment, ADA is not treatment-emergent 
ADA-positive. 
Next, using the sample ADA status, subject ADA status is defined. 
6.10.1.2. Subject ADA Status: 
• Baseline ADA-positive subject: A subject with baseline ADA-positive sample.  
• ADA-positive subject:  An evaluable subject with at least one treatment-emergent 
ADA sample at any time during the study. 
• Neutralizing-positive: At least one treatment-emergent ADA-positive sample with 
neutralizing antibodies detected (if available). 
• ADA-negative subject: An evaluable patient without a treatment-emergent ADA 
sample during the study. 
6.10.2. 
Statistical Analysis for Characterization of ADA Immune Response 
6.10.2.1. Incidence of ADA 
• Percentage of treatment-emergent ADA patients for the defined study period, where 
the denominator is the number of ADA evaluable patients in the respective treatment 
arm and/or subgroup. 
• Number (%) of subjects will be reported for the following parameters based on 
evaluable subjects: 
− Baseline ADA-positive 
− ADA-positive (Treatment-induced, Treatment-boosted) 
− Neutralizing Positive (if available) 
− ADA-negative 
• ADA prevalence: Percentage of treatment-emergent ADA patients at any given 
timepoint, where the denominator is the number of ADA evaluable patients in the 
respective treatment arm and/or subgroup at that time point. 
• A listing of all ADA assessments will be provided.  
• Additionally, a separate listing of ADA assessments for all neutralizing antibody 
(NAb)-positive subjects will be provided (if available). 
6.10.2.2. ADA Titer Kinetics  
All ADA-positive subjects will be included in the analysis. 


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• Summary statistics of subject-level ADA titers using the maximum titer value within 
an ADA positive subject will be presented for baseline ADA-negative subjects and 
baseline ADA positive subjects. The median, interquartile range, and range of the 
maximum titers will be reported. For ADA-positive subjects with baseline ADA-
positive sample, the median and interquartile range of the fold increase from baseline 
in titer (ratio of maximum post-baseline titer to baseline titer) will also be reported. 
Graphical presentation of the summary data may be provided using boxplots, as 
appropriate. 
• For sample-level ADA titers, boxplots of ADA titers at each assessment timepoint 
will be provided, as appropriate, to demonstrate whether the ADA levels tend to 
change over time during the treatment, along with ADA incidence at each assessment 
timepoint. 
• Spider plots may be considered to show the trend of ADA titer over time for subjects 
with >/= 5 ADA results by splitting subjects into multiple spider plots (e.g., ≈ ≤10 
per plot, approximately. 
6.10.3. 
Clinical Implication of ADA Immune Response 
6.10.3.1. PK 
• Effect of ADA response on the drug exposure will be explored by examining the drug 
exposures in subjects with ADA-positive versus ADA-negative status using graphical 
plots or simple summary statistics of observed drug concentration levels by sampling 
time. Corresponding numerical values of geometric mean, arithmetic mean, and 
standard deviation for each of ADA-positive subjects and ADA-negative subjects will 
be displayed under the figures.  
• A listing of drug concentration with immunogenicity assessment at each pre-specified 
time point will be provided. Time course of observed concentrations by study visit 
with identifiers for antibody response will be plotted for each subject separately. 
6.10.3.2. Safety 
• Effect of ADA response on safety will be explored by examining the frequency and 
type of AEs of interest, including (1) Total TEAEs, (2) Drug Hypersensitivity, and (3) 
Infusion Reactions. For each category of AEs, summary tables for incidence will be 
provided for each of the preferred terms and overall within a category by ADA status, 
if the number of ADA-positive subjects is of sufficient size (e.g., at least ≈10 
subjects). Otherwise, individual subject’s safety profile will be examined and 
described based on a listing.  
• Listings of AEs will be provided. These listing will also indicate study day and study 
period of the positive responses. 
6.10.3.3. Efficacy 
• Primary efficacy endpoint will be presented by ADA status.   


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• Efficacy listings for all positive subjects (relative to baseline) will be provided. These 
listing will also indicate study day and study period of the positive responses. 
7. 
CHANGES FROM PROTOCOL 
• Randomization stratification factor (Exon deletion status = yes, no) was dropped from all 
analysis models due to the small sample size in one of the factor levels. 
• Cumulative Loss of Function Analysis (Section 6.6.1.2.5 ) was added as sensitivity 
analysis for the primary efficacy endpoint. 
• Proportions of subjects in 10-meter walk/run test at Week 52 was added as a secondary 
efficacy endpoint. 
• The baseline for MFT assessments is defined as the last evaluable value prior to the first 
study drug infusion (or randomization date if no infusion is received). If the assessment at 
Day 1 is not evaluable, the assessment at the Screening visit will be used. 


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8. 
REFERENCES 
1. Annexstad EJ, Lund-Petersen I, Rasmussen M. (2014) Duchenne muscular dystrophy. 
Tidsskr Nor Laegeforen. 134(14):1361-1364. 
2. Mayer OH, Finkel RS, Rummey C et al.  Characterization of Pulmonary Function in 
Duchenne Muscular Dystrophy. PediatrPulmonol. 2015; 50:487–494 
3. J. Finder et al. Pulmonary Endpoints in Duchenne Muscular DystrophyA Workshop 
Summary Am J Respir Crit Care Med Vol 196, Iss 4, pp 512–519, Aug 15, 2017 
4. S. C. Hagenbuchet al. Detection of Progressive Cardiac Dysfunction by SerialEvaluation 
of Circumferential Strain in Patients With Duchenne Muscular DystrophyAm J 
Cardiology, 2010;105:1451–1455 
5. V. Rocotti, et al. Respiratory and upper limb function as outcome measures in ambulant 
and non-ambulant subjects with Duchenne muscular dystrophy: A prospective 
multicentre study, Nweuromuscular Disorders (2019) 1-8. 
6. McDonald et al. Long-term effects of glucocorticoids on function, quality of life, and 
survival in patients with Duchenne muscular dystrophy: a prospective cohort 
study.Lancet2018; 391: 451–61. 
7. Supplement to: McDonald CM, Henricson EK, Abresch RT, et al. Long-term effects of 
glucocorticoids on function, quality of life, and survival in patients with Duchenne 
muscular dystrophy: a prospective cohort study. Lancet 2017 
8. Sun G, Haginoya K, Wu Y, et al. (2008) Connective tissue growth factor is 
overexpressed in muscles of human muscular dystrophy. J Neurol Sci 267: (1-2):48-56  
9. Szigyarto CA, Spitali P. (2018) Biomarkers of Duchenne muscular dystrophy: current 
findings. Degener Neurol Neuromuscul Dis. 8:1-13 
10. Yiu EM, Kornberg AJ. (2015) Duchenne muscular dystrophy. J Paediatr Child Health. 
51(8):759-764.  
11. Zhou L, Lu H. (2010) Targeting fibrosis in Duchenne muscular dystrophy. J Neuropathol 
Exp Neurol. 69(8):771-776. 
12. Meier T, Rummey C, Leinonen M, et al. (2017) Characterization of pulmonary function 
in 10-18 year old patients with Duchenne muscular dystrophy. Neuromuscul Disord. 
27(4):307-314  
 


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9. 
APPENDICES 


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APPENDIX 1. HANDLING MISSING/INCOMPLETE DATES 
A.1 
Missing/Incomplete AE Onset Date 
The following imputation rules apply to the case where the start date is incomplete (i.e., partially 
missing) for adverse events. 
A.1.1 Missing start time 
AEs with missing start times and which occur on a study-drug-dosing day will be considered as 
occurred after the study drug administration on that day, that is, it will be considered as TEAE. 
No imputation on other missing times. 
A.1.2 Missing day and month 
If the year is same as the year of first day on double-blind study medication, then the day and 
month of the start date of double-blind study medication will be assigned to the missing fields. 
If the year is not the same as the year of first day on double-blind study medication, then January 
1 will be assigned to the missing fields. 
A.1.3 Missing month only 
Treat day as missing and replace both month and day according to the above procedure. 
A.1.4 Missing day only 
If the month and year are same as the year and month of first day on double-blind study 
medication, then the start date of double-blind study medication will be assigned to the missing 
day. 
If the month and year are not the same as the year and month of first day on double-blind study 
medication, then the first day of the month will be assigned to the missing day. 
Table 4: 
Analysis Date Derivation Rules for Missing/Incomplete AE Onset Date 
Reported Date 
Date of First Drug Intake 
Analysis Date (Derived) 
--/MM/YYYY 
--/02/2008 
--/02/2008 
--/02/2008 
DD/MM/YYYY 
14/02/2008 
14/02/2007 
14/02/2009 
 
14/02/2008* 
01/02/2008 
01/02/2008  
--/--/YYYY 
--/--/2008 
--/--/2008 
--/--/2008 
DD/MM/YYYY 
14/02/2008 
14/02/2007 
14/02/2009 
 
14/02/2008 
01/01/2008 
01/01/2008  
DD/--/---- 
--/MM/---- 
--/--/---- 
 
No imputation  
*Death date has to be taken into consideration when calculating this. 
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. 
A.2 
Missing/Incomplete AE Stop Date 


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If needed, the following imputation rules apply to the case where the end date is incomplete 
(i.e., partially missing) for adverse events. Other partial end dates will not be imputed. 
A.2.1  
Missing day and month, or Missing month only 
December 31 will be assigned to the missing fields. 
A.2.2  
Missing day only 
The last day of the month will be assigned to the missing day. 
Table 5: 
Analysis Date Derivation Rules for Missing/Incomplete AE Stop Date 
Reported Date 
Analysis Date (Derived) * 
--/MM/YYYY 
Set as last day of the month 31/MM/YYYY or 
30/MM/YYYY or 
29/MM/YYYY or 
28/MM/YYYY 
--/--/YYYY 
31/12/YYYY 
DD/--/---- 
No imputation  
--/MM/---- 
--/--/---- 
*Death date has to be taken into consideration when deriving this. 
 
A.3 
 
Missing/Incomplete Prior or Concomitant Medication Start Date 
For prior or concomitant 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. 
The following rules will be applied to impute the missing start date. If the stop date is complete 
and the imputed start date is after the stop date, then the start date will be imputed using the stop 
date. 
A.3.1 Missing day and month 
If the year of the incomplete start date is the same as the year of the first dose date of double-
blind study medication, then the day and month of the first dose date will be assigned to the 
missing fields. 
If the year of the incomplete start date is not the same as the first dose date of double-blind study 
medication, then January 1 will be assigned to the missing fields. 
A.3.2 Missing month only 
Treat day as missing and replace both month and day according to the above procedure. 
A.3.3 Missing day only 
If the month and year of the incomplete start date are the same as the month and year of the first 
dose date of double-blind study medication, then the day of the first dose date will be assigned to 
the missing day. 


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If the month and year of the incomplete start date are the same as the first dose date of double- 
blind study medication, then the first day of the month will be assigned to the missing day. 
A.4 
 
Missing/Incomplete Prior or Concomitant Medication Stop Date 
The following rules will be applied to impute the missing stop date, if needed.  If the last dose 
date of double-blind study medication is missing, impute it with the last visit date. If the imputed 
stop date is before the start date (imputed or non-imputed start date), then the imputed stop date 
will be replaced with the start date. 
A.4.1 Missing day and month 
If the year of the incomplete stop date is the same as the year of the last dose date of double- 
blind study medication, then the day and month of the last dose date will be assigned to the 
missing fields. 
If the year of the incomplete stop date is not the same as the year of the last dose date of double-
blind study medication, then December 31 will be assigned to the missing fields. 
A.4.2 Missing month only 
Treat day as missing and replace both month and day according to the above procedure. 
A.4.3 Missing day only 
If the month and year of the incomplete stop date are the same as the month and year of the last 
dose date of double-blind study medication, then the day of the last dose date will be assigned to 
the missing day. 
If the month and year of the incomplete stop date are not the same as the month and year of the 
last dose date of double-blind study medication, then the last day of the month will be assigned 
to the missing day. 
A.5 
 
Missing Date Imputation for Last Dose Date 
Imputed last dose date = earliest date of (last drug dispense date + number of days of drug 
dispensed, date of death, date of EOT/EOS visit, and other dates as appropriate). 
 


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APPENDIX 2. ANALYSIS VISIT WINDOWS 
A.2. Analysis Windows 
Analysis visits are defined by the windows that will have the widths of the corresponding 
assessments centered at the scheduled time. Unscheduled visits within a visit window defined 
below will be grouped into the closest scheduled visits based on the visit date. 
Table 6: 
Analysis Visit Window for Vital Signs 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last value before the first study drug infusion (or 
randomization date if no infusion received) 
Day 1 post-dose 
1 
1 
1 
Week 2 
15 
2 
22 
Week 4 
29 
23 
36 
Week 6 
43 
37 
50 
Week 8 
57 
51 
64 
Week 10 
71 
65 
78 
Week 12 
85 
79 
92 
Week 14 
99 
93 
106 
Week 16 
113 
107 
120 
Week 18 
127 
121 
134 
Week 20 
141 
135 
148 
Week 22 
155 
149 
162 
Week 24 
169 
163 
176 
Week 26 
183 
177 
190 
Week 28 
197 
191 
204 
Week 30 
211 
205 
218 
Week 32 
225 
219 
232 
Week 34 
239 
233 
246 
Week 36 
253 
247 
260 
Week 38 
267 
261 
274 
Week 40 
281 
275 
288 
Week 42 
295 
289 
302 
Week 44 
309 
303 
316 
Week 46 
323 
317 
330 
Week 48 
337 
331 
344 
Week 50 
351 
345 
358 
Week 52 
365 
359 
** 
** before the first study drug infusion in the OLE period or end of randomization treatment period 
Note: The data on a study day with infusions will be used as a priority for summary tables whenever possible. 
Note: All assessments beyond 60 days post last infusion will be excluded from summary tables or figures. 


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Table 7: 
Analysis Visit Window for Physical Examination  
Analysis Visit 
Target Day 
Start Day End Day 
Baseline 
Last value before the first study drug infusion (or randomization 
date if no infusion received) 
Week 12 
85 
2 
127 
Week 24 
169 
128 
211 
Week 36 
253 
212 
309 
Week 52 
365 
310 
** 
** before the first study drug infusion in the OLE period or end of randomization treatment period  
Note: All assessments beyond 60 days post last infusion will be excluded from summary tables for labs. 
 
Table 8: 
Analysis Visit Window for Pulmonary Function Tests (PFT) 
 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
Last value before the first study drug infusion (or randomization 
date if no infusion received) 
Week 12 
85 
2 
120 
Week 22 
155 
121 
190 
Week 32 
225 
191 
260 
Week 42 
295 
261 
330 
Week 52 
365 
331 
** 
** before the first study drug infusion in the OLE period or end of randomization treatment period  
Note: All assessments beyond 60 days post last infusion will be excluded from summary tables for labs. 
 
Table 9: 
Analysis Visit Window for Muscle Function Tests (MFT) 
 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline* 
Last value before the first study drug infusion (or randomization 
date if no infusion received) 
Week 10 
71 
2 
106 
Week 20 
141 
107 
176 
Week 30 
211 
177 
246 
Week 40 
281 
247 
323 
Week 52 
365 
324 
** 
* Please refer to the Section 7 for details 
** Before the first study drug infusion in the OLE period or end of randomization treatment period  
Note: All assessments beyond 60 days post last infusion will be excluded from summary tables for labs. 
 
 


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Table 10: 
Analysis Visit Window for Laboratory Tests  
Analysis Visit 
Target Day 
Start Day End Day 
Baseline 
Last value before the first study drug infusion (or randomization 
date if no infusion received) 
Week 8 
57 
2 
85 
Week 16 
113 
86 
141 
Week 24 
169 
142 
197 
Week 32 
225 
198 
253 
Week 40 
281 
254 
309 
Week 48 
337 
310 
365 
Week 56 
393 
366 
** 
** before the first study drug infusion in the OLE period or end of randomization treatment period  
Note: All assessments beyond 60 days post last infusion will be excluded from summary tables for labs. 
 
Table 11: 
Analysis Visit Window for Immunogenicity Data  
Analysis Visit 
Target Day 
Start Day End Day 
Baseline 
Last value before the first study drug infusion (or randomization 
date if no infusion received) 
Week 24 
169 
2 
197 
Week 32 
225 
198 
253 
Week 40 
281 
254 
309 
Week 48 
337 
310 
** 
** before the first study drug infusion in the OLE period or end of randomization treatment period  
 
 


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APPENDIX 3. NORTH STAR AMBULATORY ASSESSMENT (NSAA)   
The North Star Ambulatory Assessment (NSAA) worksheet should be used to document the 
scores for the assessments.  A separate manual will be provided as a guide on how the tests 
should be conducted.  
Note: The Time to Stand (from Supine) test is called Rise from Floor and is contained within the 
NSAA. 
 
Activity 
2 
1 
0 
Score 
1. Stand 
*3 
Stands upright, still, symmetrical, 
without compensation (heels flat and 
hips in neutral rotation) for minimum 
count of 3 seconds 
Stands still but with compensation (e.g. 
on toes or with legs abducted or with 
bottom stuck out/hip flexion, etc.) for 
minimum count of 3 seconds 
Cannot stand still or cannot 
stand independently, needs 
support (even minimal) 
2. Walk 
*3 
Walks consistently with heel-toe or flat- 
footed gait pattern 
Persistent or habitual toe walker, unable 
to heel-toe consistently 
Loss of independent ambulation 
– may use knee-ankle-foot 
orthosis (KAFO) or walk short 
distances with assistance 
3. Stand up 
from chair 
*3 
Able to stand up keeping arms folded 
With help from thighs / push on chair / 
prone turn or alters starting position by 
widening base (moving feet apart) 
Unable 
4. Stand on 
one leg – 
right *3.5 
Able to stand upright in a relaxed 
manner (no fixation) for a count of 3 
seconds 
Stands but either momentarily or with 
trunk side-flexion (20◦) or needs fixation 
e.g. by thighs adducted 
Unable 
5. Stand on 
one leg – left 
*3.5 
Able to stand upright in a relaxed 
manner (no fixation) for a count of 3 
seconds 
Stands but either momentarily or with 
trunk side-flexion (20◦) or needs fixation 
e.g. by thighs adducted 
Unable 
6. Climb box 
step – right 
*3 
Faces step – no support needed 
Goes up sideways / rotates trunk / 
circumducts hip / needs hands for 
balance or hands on legs 
Unable to perform 
independently 
7. Descend 
box step – 
right *3.5 
Faces forward, steps down controlling 
weight-bearing leg. No support needed 
Sideways / skips down / needs hands for 
balance or hands on legs 
Unable without more than 
minimal support, or requires 
hands for support 
8. Climb box 
step – left *3 
Faces step – no support needed 
Goes up sideways / rotates trunk / 
circumducts hip / needs hands for 
balance or hands on legs 
Unable to perform 
independently 
9. Descend 
box step -left 
*3.5 
Faces forward, steps down controlling 
weight-bearing leg. No support needed 
Sideways / skips down / needs hands for 
balance or hands on legs 
Unable without more than 
minimal support, or requires 
hands for support 
10. Lifts head 
*4 
In supine, full neck flexion, head must be 
lifted in mid-line. Chin moves towards 
chest 
Head is lifted through side flexion, partial 
neck flexion, or with protraction 
Unable. No clearance of head 
from surface 
11. Gets to 
sitting *3 
Starts in supine – may use one hand / 
arm to push up 
Uses two arms / pulls on legs or turns 
towards floor or uses momentum/rocking 
Unable 


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12. Rise from 
floor *4 
No evidence of Gower’s maneuver 
Exhibits at least one of the components 
described above – in particular rolls 
towards floor, and/or use hand(s) on legs 
(a) NEEDS to use external 
support object e.g. chair, wall 
OR (b) Unable NO TIME 
RECORDED 
13. Stands 
on heels *3.5 
Both feet at the same time, clearly 
standing on heels only (acceptable to 
move a few steps to keep balance) for 
count of 3 
Raises forefoot on both feet – all 
metatarsal heads off ground – or clearly 
dorsiflexes one foot only 
Unable 
14. Jump *3 
Both feet at the same time, clear the 
ground simultaneously and land at the 
same time 
One foot after the other (skip) or does 
not fully clear both feet at the same time 
Unable 
15. Hop right 
leg *4 
Entire foot clears the floor 
Able to bend knee AND raise heel, no 
floor clearance 
Unable or only raises heel 
16. Hop left 
leg *4 
Entire foot clears the floor 
Able to bend knee AND raise heel, no 
floor clearance 
Unable or only raises heel 
17. Walk Run 
(10 m) *3 
Both feet off the ground (no double 
stance phase during running) 
‘Duchenne jog’ or fast walk 
Walk 
TOTAL= 
/34 
 
 


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APPENDIX 4. LABORATORY TEST CTCAE CRITERIA 
The following table is extracted from NCI Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0  
Chemistry 
  
  
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Bicarbonate 
Decreased <LLN and no 
intervention 
initiated 
None 
None 
None 
Creatinine 
  
ULN – 1.5 x 
ULN 
>1.5 – 3.0 x 
baseline[2] 
>1.5 – 3.0 x ULN 
>3.0 x baseline[2] 
>3.0 – 6.0 x ULN 
>6.0 x ULN 
Albumin 
Decreased 3 g/dL – LLN 
2 - <3 g/dL 
<2 g/dL 
  
Alkaline 
phosphatase 
(ALP) 
  
ULN – 2.5 x 
ULN[4]; 2.0 - 2.5 
x baseline[5] 
>2.5 – 5.0 x 
ULN[4]; >2.5 - 5.0 
x baseline[5] 
>5.0 – 20.0 x 
ULN[4]; >5.0 - 
20.0 x baseline[5] 
> 20.0 x ULN[4]; 
>20.0 x baseline[5] 
ALT 
  
ULN – 3.0 x 
ULN[4]; 1.5 - 3.0 
x baseline[5] 
>3.0 – 5.0 x 
ULN[4]; >3.0 - 5.0 
x baseline[5] 
>5.0 – 20.0 x 
ULN[4]; >5.0 - 
20.0 x baseline[5] 
>20.0 x ULN[4]; 
>20.0 x baseline[5] 
AST 
  
ULN – 3.0 x 
ULN[4]; 1.5 - 3.0 
x baseline[5] 
>3.0 – 5.0 x 
ULN[4]; >3.0 - 5.0 
x baseline[5] 
>5.0 – 20.0 x 
ULN[4]; >5.0 - 
20.0 x baseline[5] 
>20.0 x ULN[4]; 
>20.0 x baseline[5] 
Total bilirubin 
  
ULN – 1.5 x 
ULN[4]; > 1.0 - 
1.5 x baseline[5] 
>1.5 – 3.0 x 
ULN[4]; >1.5 - 3.0 
x baseline[5] 
>3.0 – 10.0 x 
ULN[4]; >3.0 - 
10.0 x baseline[5] 
>10.0 x ULN[4]; 
>10.0 x baseline[5] 
Calcium 
(Corrected) 
Decreased 8.0 mg/dL – 
LLN 
7.0 - <8.0 mg/dL 6.0 - <7.0 mg/dL 
<6.0 mg/dL 
  
  
ULN – 11.5 
mg/dL 
>11.5 – 12.5 
mg/dL 
>12.5 – 13.5 
mg/dL 
>13.5 mg/dL 
Glucose 
(Random) 
Decreased 55 mg/dL – LLN 40 - <55 mg/dL 
30 - <40 mg/dL 
<30 mg/dL 
Potassium 
Decreased 3.0 mmol/L – 
LLN 
3.0 mmol/L – 
LLN[1] 
2.5 - <3.0 mmol/L <2.5 mmol/L 
  
  
ULN – 5.5 
mmol/L 
>5.5 – 6.0 
mmol/L[3] 
>6.0 – 7.0 mmol/L >7.0 mmol/L 
Sodium 
Decreased 130 mmol/L – 
LLN 
125-129 mmol/L 
and 
asymptomatic 
125-129 mmol/L 
symptomatic; 120-
124 mmol/L 
regardless of 
symptoms 
<120 mmol/L 
  
  
ULN – 150 
mmol/L 
>150 – 155 
mmol/L[3] 
>155 – 160 
mmol/L 
>160 mmol/L 
Magnesium 
Decreased 1.2 mg/dL – 
LLN 
0.9 - <1.2 mg/dL 0.7 - <0.9 mg/dL 
<0.7 mg/dL 


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ULN – 3.0 
mg/dL 
None 
>3.0 – 8.0 mg/dL >8.0 mg/dL 
 
Serum Hematology 
  
  
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
Decreased 10.0 g/dL – LLN 8.0 - <10.0 g/dL 
<8.0 g/dL 
  
  
  
>0 – 2 g/dL 
>2 – 4 g/dL 
>4 g/dL 
  
Platelet 
Decreased 75,000 /mm3 – 
LLN 
50,000 – <75,000 
/mm3 
25,000 - <50,000 
/mm3 
<25,000 /mm3 
WBC 
Decreased 3,000 /mm3 – LLN 2,000 - <3,000 
/mm3 
1,000 - <2,000 
/mm3 
<1,000 /mm3 
  
  
None 
None 
>100,000 /mm3 
  
aPTT 
  
ULN – 1.5 x ULN >1.5 – 2.5 x ULN >2.5 x ULN 
  
Lymphocytes 
Decreased 800 /mm3 – LLN 500 - <800 /mm3 200 - <500 /mm3 <200 /mm3 
  
  
None 
>4,000 – 20,000 
/mm3 
>20,000 /mm3 
  
Neutrophils 
Decreased 1500 /mm3 - LLN 1000 - <1500 
/mm3 
500 - <1000/mm3 <500/mm3 
Eosinophils 
 
>ULN and 
>Baseline 
None 
Steroids initiated None 
Decreased: below LLN; Otherwise, above ULN; 
[1] Symptomatic, Intervention indicated 
[2] Baseline is used if it is above ULN 
[3] Intervention indicated 
[4] ULN is used if Baseline was normal 
[5] Baseline is used if Baseline was abnormal 


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APPENDIX 5. GENERAL SPECIFICATIONS FOR TABLES, LISTINGS, 
FIGURES 
1. 
Software Used 
All programming of tables, listings and figures (TFLs) will be performed using the statistical 
software package SAS version 9.4 or greater. 
2. 
General  
All TFLs are based on Study Data Tabulation Model (SDTM) and/or Analysis Data Model 
(ADaM) datasets. By default, data listings reflect the actual values captured in SDTM and 
ADaM datasets, including date/time variables and missing values. Except for concatenation of 
some variables for compact display purpose, data are presented directly with minimum 
manipulation. In general, the character standard result variables is presented in data listings.  
For continuous variables that are recorded as “<X” or “>X”, the value of “X” will be used in the 
calculation of summary statistics. The value “X” is also captured in the numeric variable in the 
SDTM datasets as well as in the ADaM datasets for consistency, although SDTMIG 
recommends capturing missing values in the numeric variables.  
3. 
Page Layout 
All column headers (consisting of one or several words) will start with uppercase and thereafter 
only lowercase characters, except for acronyms and abbreviations. In case values from the 
database will be displayed in column headers, they may be displayed as in the database. Pages 
will be numbered as ‘Page x of y’, where ‘y’ is the total number of pages of the corresponding 
table or listing. The page specifications are presented in Table 3. 
Table 12: 
Specifications for Page Layout 
Paper Size 
Letter 
Orientation 
Landscape 
Alignment 
Center 
Font size 
9 
Font type 
Courier New (default) 
Margins: 
 
   Top 
1.0” 
   Bottom 
0.4” 
   Left 
1.0” 
   Right 
0.4” 
The margin sizes and font size for listings may be flexible to provide sufficient information on a 
single page to facilitate review and comparison. 
When created using SAS, tables and listings will be created using ODS, and output files will be 
produced in RTF. When RTF files are produced, titles and footnotes will appear as document 
headers/footers. 


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4. 
Titles and Footnotes 
All tables and listings will have a header showing “FibroGen, Inc.”, the protocol number, 
database cutoff date or ‘Final Database’, and Page x of y. A footer will show the program file 
path/name, output file path/name, run date and time.  
All titles are written in title format, with uppercase at the beginning of each word; articles, 
prepositions, and conjunctions, which are of three characters length or less will start with 
lowercase letters (Mixed Case).  Footnotes are in regular text format. 
Titles 
In total there are up to 10 titles available, defined as following: 
first title 
“FibroGen, Inc.” (left aligned) and “Date of Data Cutoff : ddMMMyyy” (right 
aligned) 
second title 
protocol number “Protocol: FGCL-3019-093 (LELANTOS(NA))” (left aligned) 
and “Page x of y” (right aligned) 
third title 
blank 
fourth title: 
table/listing/figure number 
fifth title:         table/listing/figure title 
sixth title:  
population names if provided in SAP, or brief definition of specific analysis set 
Footnotes 
Up to 10 footnote lines are available for tables, listings and figures. Footnotes 1, 9 and 10 are 
standard. Footnotes 2 to 8 (left aligned) might be used as needed. They are to be specified in the 
Shell.  
first footnote  
is a separating horizontal line. 
second – eighth 
are free text which can be used for explanations. Footnotes will be 
referenced using numbers in square brackets, starting with [1], followed by [2] etc.  
ninth footnote left blank; in case needed may also be used as for explanations. 
tenth footnote the program name and the date of data extraction (left aligned); the date and time 
in the format ddMMMyyyy hh:mm when the output was created; the version (e.g. draft or final); 
and the word “Confidential”.  
Footnotes are denoted by [1], [2], and so on.   
5. 
Table, Figure, Listing Metadata 
The table, figure, and listing (TFL) metadata will include the TFL numbers, titles, analysis 
populations, program names, input dataset names. For tables and figures, PARAMCD, PARAM, 
and other conditions will be specified. TFL numbers, titles, and footnotes will be imported from 
this master spreadsheet. In addition, this spreadsheet will record the names of the original 
programmer and the validator/reviewer and the date of validation approval. 


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6. 
Significant Digits of Summary Statistics 
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. 
Any p-values will be rounded to four decimal places and will be presented as ‘<.0001’ if they are 
less than 0.0001 after rounding. 
For variables of direct measurements, summary statistics are displayed with the following 
specifications of decimal places in Table 13. 
Table 13: 
 
Significant Digits of Summary Statistics 
Description 
Characteristic Number of decimal places 
Count 
N 
0 
Mean 
Mean 
As in source + 1 
Standard deviation 
SD 
As in source + 2 
Standard error of the mean SE 
As in source + 2 
Confidence Interval 
CI 
As in source + 1 
Minimum 
Min  
As in source 
Median 
Median 
As in source + 1 
Maximum 
Max 
As in source 
Q1  /  Q3 
Q1/Q3 
As in source + 1 
Percentage 
% 
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 
Coefficient of variation 
CV (%) 
1 
p-value 
p-value 
p-values will be rounded to four decimal places 
and will be presented as ‘<.0001’ if they are less 
than 0.0001 after rounding 
N=number; Std=Standard deviation; CI=Confidence Interval; Min=minimum; 
Max=maximum; CV=Coefficient of variation 
As a general guideline for derived parameters, three significant digits may be displayed for a 
parameter with an overall mean less than 100; otherwise, one decimal place may be used. If a 
derived parameter is in the same scale as some related measured parameters, such as MAP, QTc, 
the same display format may be used as the measured parameters. 
Summary Statistics are to be displayed in the following order: Count, Mean, Standard Deviation, 
<Coefficient of Variation, Standard Error of the Mean, Confidence Interval>, Minimum, <Q1>, 
Median, <Q3>, Maximum. 
For categorical variables the categories will be displayed in the TFLs in the same order they 
appear in the CRF. 
7. 
Figure Specifications 
In general, figures should include annotation of key summary statistics: n, mean, SE, median for 
continuous variables; n and percent for categorical variables; number of subjects at risk and 


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cumulative number of events as well as median and 95% CI for time-to-event data. Other 
statistics such as quartiles, ranges may be included depending on need and space.  
P-values should be presented if comparisons are of interest. 
For scatter plots, linear or non-linear trend lines should be included if the association of the two 
variables is of interest. Correlation coefficient or regression coefficients as well as corresponding 
p-values should be presented. 
For box plots, ‘BOXSTYLE=SCHEMATIC’ should be used. The whiskers are drawn to the 
most extreme points in the group that lie within the fences. The upper fence is defined as the 
third quartile (represented by the upper edge of the box) plus 1.5 times the interquartile range. 
The lower fence is defined as the first quartile (represented by the lower edge of the box) minus 
1.5 times the interquartile range. Observations outside the fences are identified with a special 
symbol. 
 
 


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APPENDIX 6. CHINA CDE REQUIREMENTS 
Efficacy data, mainly including overseas key clinical trial data and clinical trial data conducted 
in China, should not only confirm the efficacy of the study drug as a whole, but also analyze the 
consistency between Chinese subgroups and the overall population.  
The point estimate of treatment effect in China subgroup divided by its counterpart in the overall 
population will be used for assessing efficacy consistency. 
Safety data, including all domestic and foreign data used for safety evaluation, should be 
analyzed not only for overall safety, but also for consistency between Chinese subgroup and 
overall population. 
All TFLs in China may be provided per China regulatory requirements if regulatory submission 
in China is pursued. 
 
 


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