Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne Muscular Dystrophy, DMD
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 98
Healthy volunteers: no

Brief summary:
To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids in participants with non-ambulatory Duchenne muscular dystrophy (age 12 years and older).

Detailed description:
This is a global, Phase 3, randomized, double-blind trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with non-ambulatory Duchenne muscular dystrophy, aged 12 years and older. Approximately 90 male participants will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic corticosteroid) or Arm B (placebo+ systemic corticosteroid), respectively.

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

This trial has 3 study periods:

* Screening period: Up to 4 weeks
* Treatment period: 52 weeks
* 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

In the screening period, participants will be evaluated per the protocol inclusion/exclusion criteria to determine eligibility for participation in this trial.

During the treatment period, each participant will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks.

Participants who complete the 52-week study (either arm) may be eligible for rollover into an open-label extension treatment (OLE) with pamrevlumab + systemic corticosteroids.

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 per dose and schedule specified in the arm description intervention 2: Matching placebo per schedule specified in the arm description intervention 3: Systemic deflazacort or equivalent potency of corticosteroids administered orally

Protocol document:
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 Subjects with Non- 
ambulatory Duchenne Muscular Dystrophy (DMD) 
PROTOCOL NUMBER: 
FGCL-3019-093 
PHASE: 
Phase 3 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
KEY SPONSOR CONTACT(S): 
EUDRACT NUMBER: 
Name: 
 
Title: 
 
Mobile:  
 
E-mail Address:  
2020-000698-26 
IND NUMBER: 
126630 
STUDY DRUG: 
Pamrevlumab (FG-3019) 
INDICATION: 
Duchenne Muscular Dystrophy 
ORIGINAL PROTOCOL: 
Amendment 1: 
Amendment 2: 
Amendment 3: 
Amendment 4: 
Amendment 5: 
Amendment 6: 
20 December 2019 
13 February 2020 
10 April 2020 
15 September 2020 
26 October 2020 
09 July 2021 
01 November 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.
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Page 1 of 84
NCT #: NCT04371666


Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
INVESTIGATOR SIGNATURE PAGE 
STUDY ACKNOWLEDGEMENT 
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) 
FGCL-3019-093 
Original: 20 December 2019 
Amendment 1: 13 February 2020 
Amendment 2: 10 April 2020 
Amendment 3: 15 September 2020 
Amendment 4: 26 October 2020 
Amendment 5: 09 July 2021 
Amendment 6: 01 November 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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Pamrevlumab 
Protocol FGCL-3019-093 A6 
CONFIRMATION OF PROTOCOL APPROVAL 
Original Protocol Date: 20 December 2019 
Amendment 1: 13 February 2020 
Amendment 2: 10 April 2020 
Amendment 3: 15 September 2020 
Amendment 4: 26 Oct 2020 
Amendment 5: 09 July 2021 
Amendment 6: 01 November 2022 
This protocol is approved by FibroGen. 
 
 
FibroGen, Inc. 
Date 
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Page 3 of 84
See appended final page for 
21CFR Part 11 compliant approval


Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
AMENDMENT 6.0: KEY CHANGES 
The protocol has been edited for clarity, consistency, and quality of content (typographical 
errors, 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 
Added bone fracture safety 
assessments 
To align with the pediatric 
investigational plan 
Synopsis, Section 3.1.1.3, 
Appendix 1 Schedule of 
Assessments, Appendix 3 Open 
Label Extension 
Re-arranged secondary 
endpoint 
Changed to align with revised 
analysis plan 
Synopsis, 3.1.1.2 Secondary 
Endpoints 
Added exploratory 
endpoint 
To summarize subscores of 
three regional dimensions of 
PUL 
Synopsis, Section 3.1.1.4, 
Section 8.3.4.2. 
Effect size, treatment 
difference, and common 
standard deviation revised 
Numbers revised to reflect PUL 
V2.0 
Synopsis, Section 8.1 
Updated eligibility criteria 
Clarifications to Inclusion 
Criteria 3, 10 and 12, and 
Exclusion Criteria 5c 
Eligibility Criteria 
Removed preliminary 079 
data 
Completed 079 study results 
now available and presented in 
the latest Investigator Brochure 
Section 2.5, Section 2.6 
Updated withdrawal 
criteria  
To include description for 
patients discontinuing infusions 
Section 4.3 
Additional PK, HAHA, 
HAHA-NA and 
immunogenic reaction 
blood draws 
Increased testing for 
immunogenicity assessments 
and to include local guidelines 
to be followed for total blood 
volume 
Section 6.2.3.2.3, Appendix 2, 
Appendix 3 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
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 5.1.4 
Added preliminary non-
clinical study results 
Preliminary results of rabbit 
embryo-fetal development study 
available to inform contraception
recommendations 
Section 5.2.3 
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 
Clarified China will not 
perform DMD video 
assessments 
Due to Regulatory guidelines 
this assessment will not be 
performed in China 
Section 6.2.7 
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 6.2.4 
HAHA-NA Sample 
Further clarification regarding 
drawing of additional HAHA-
NA sample 
Appendix 2  
Added clarification on first 
visit for patients entering 
the Open Label Extension 
portion of the trial and 
when End of Study visit 
takes place  
For added clarity  
Appendix 3 Open Label 
Extension 
Added timeframe of 
“within an 8 week period” 
to the OLE missed doses 
language. 
To align with the main study 
Appendix 3 Open Label 
Extension 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
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 
 
 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
TABLE OF CONTENTS 
 
 
CONFIRMATION OF PROTOCOL APPROVAL .........................................................................3 
AMENDMENT 6.0: KEY CHANGES ...........................................................................................4 
TABLE OF CONTENTS .................................................................................................................7 
LIST OF ABBREVIATIONS ........................................................................................................12 
1. 
PROTOCOL SYNOPSIS ...........................................................................................15 
2. 
INTRODUCTION ......................................................................................................21 
2.1. 
Description of Pamrevlumab ......................................................................................21 
2.2. 
Duchenne Muscular Dystrophy ..................................................................................21 
2.3. 
Connective Tissue Growth Factor ..............................................................................22 
2.4. 
Connective Tissue Growth Factor in Duchenne Muscular Dystrophy .......................23 
2.5. 
Clinical Trial Experience with Pamrevlumab .............................................................23 
2.6. 
Rationale and Risk/Benefit for Pamrevlumab in Duchenne Muscular 
Dystrophy ...................................................................................................................24 
2.6.1. 
Rationale .....................................................................................................................24 
2.6.2. 
Primary endpoint: Performance of the upper limb .....................................................25 
2.6.3. 
Secondary endpoint: Forced vital capacity .................................................................25 
2.6.4. 
Secondary Endpoint: Peak Expiratory Flow Rate (PEFR) .........................................25 
2.6.5. 
Secondary endpoint: Grip Strength assessed by Hand-Held Myometry 
(HHM) ........................................................................................................................25 
2.6.6. 
Secondary endpoint: Left ventricular ejection fraction percentage (LVEF %) ..........26 
2.6.7. 
Forced Expiratory Volume at 1 Second (FEV1) ........................................................26 
2.6.8. 
Fibrosis and FAT assessment of the Upper Arm (Biceps brachii) assessed 
by MRI ........................................................................................................................26 
2.7. 
Dose Rationale Pharmacokinetics ..............................................................................27 
2.7.1. 
Single-Dose Idiopathic Pulmonary Fibrosis Study FGCL-MC3019-002 ..................27 
2.7.2. 
Single and Multiple-dose PK in Subjects with Incipient Nephropathy Due to 
Type 1 or Type 2 Diabetes Mellitus (FGCL-3019-MC003) ......................................27 
2.7.3. 
Multiple-Dose Idiopathic Pulmonary Fibrosis Study FGCL-3019-049 .....................28 
2.7.4. 
Multiple-Dose Pancreatic Cancer Study FGCL-MC3019-028 ...................................28 
2.7.5. 
Single Dose PK in DMD subjects in Study FGCL-3019-079 ....................................29 
2.8. 
Safety Summary ..........................................................................................................29 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................31 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
3.1. 
Objective .....................................................................................................................31 
3.1.1. 
Endpoints ....................................................................................................................31 
3.2. 
Overall Study Design ..................................................................................................32 
3.2.1. 
Study Duration ............................................................................................................33 
3.2.2. 
Placebo Control Group ...............................................................................................33 
3.3. 
Subject ID Assignment ...............................................................................................33 
3.4. 
Randomization and Treatment Assignment ................................................................34 
3.4.1. 
Randomization ............................................................................................................34 
3.4.2. 
Treatment Assignment ................................................................................................34 
3.5. 
Blinding ......................................................................................................................34 
3.5.1. 
Maintenance of Blinding ............................................................................................34 
3.5.2. 
Request for Unblinding of Treatment Assignment .....................................................34 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................35 
4.1. 
Subject Inclusion Criteria ...........................................................................................35 
4.2. 
Subject Exclusion Criteria ..........................................................................................36 
4.3. 
Subject Withdrawal Criteria .......................................................................................37 
4.4. 
Subject Withdrawal Procedure ...................................................................................37 
4.5. 
Replacement of Study Subjects ..................................................................................37 
4.6. 
Study Termination ......................................................................................................37 
5. 
TREATMENT OF SUBJECTS ..................................................................................39 
5.1. 
Study Treatment ..........................................................................................................39 
5.1.1. 
Pamrevlumab or Placebo ............................................................................................39 
5.1.2. 
Study Drug Preparation ..............................................................................................39 
5.1.3. 
Study Drug (Investigational Product) Administration ................................................40 
5.1.4. 
Home Health Care ......................................................................................................41 
5.1.5. 
Missed Dose ................................................................................................................41 
5.1.6. 
Study Drug Handling and Disposal ............................................................................42 
5.1.7. 
Treatment Compliance ................................................................................................42 
5.2. 
Concomitant Medications ...........................................................................................42 
5.2.1. 
Permitted Concomitant Medications ..........................................................................42 
5.2.2. 
Prohibited Concomitant Medications .........................................................................43 
5.2.3. 
Contraception Requirements ......................................................................................43 
6. 
ASSESSMENTS OF EFFICACY ..............................................................................44 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
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 
6.2. 
Assessments ................................................................................................................45 
6.2.1. 
Vital Signs (including Weight) ...................................................................................45 
6.2.2. 
Physical Exam ............................................................................................................46 
6.2.3. 
Laboratory Evaluations ...............................................................................................46 
6.2.4. 
Muscle Function Test (MFT) ......................................................................................49 
6.2.5. 
Pulmonary Function Test (PFT) .................................................................................49 
6.2.6. 
Magnetic Resonance Imaging (MRI) .........................................................................49 
6.2.7. 
Duchenne Video Assessment .....................................................................................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 .......................................................................................................58 
8. 
STATISTICS ..............................................................................................................59 
8.1. 
Sample Size Determination ........................................................................................59 
8.2. 
Analysis Populations ..................................................................................................59 
8.2.1. 
Intent to Treat (ITT) Population .................................................................................59 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
8.2.2. 
Safety Population ........................................................................................................59 
8.3. 
Statistical Analysis ......................................................................................................59 
8.3.1. 
General Considerations ...............................................................................................59 
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. 
Exploratory analysis: ..................................................................................................61 
8.3.6. 
Pharmacokinetic Analyses ..........................................................................................62 
8.3.7. 
Safety Analyses ..........................................................................................................62 
8.4. 
Statistical Analysis Plan .............................................................................................63 
9. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................64 
9.1. 
Data Quality Assurance ..............................................................................................64 
9.2. 
Audit and Inspection ...................................................................................................64 
10. 
ETHICS ......................................................................................................................65 
10.1. 
Ethical Considerations ................................................................................................65 
10.2. 
Communication with the Institutional Review Board or Independent Ethics 
Committee ...................................................................................................................65 
10.3. 
Subject Information and Consent ...............................................................................65 
10.4. 
Subject Confidentiality ...............................................................................................66 
11. 
DATA HANDLING AND RECORD KEEPING ......................................................67 
11.1. 
Source Documents ......................................................................................................67 
11.2. 
Direct Access to Source Documents...........................................................................67 
11.3. 
Data Collection, Handling, and Verification ..............................................................67 
11.4. 
Protocol Deviations ....................................................................................................68 
11.5. 
Retention of Data ........................................................................................................68 
11.6. 
Financial Disclosure ...................................................................................................68 
12. 
PUBLICATION POLICY ..........................................................................................69 
13. 
REFERENCES ...........................................................................................................70 
APPENDICES ...............................................................................................................................74 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................75 
APPENDIX 2. PHARMACOKINETIC AND PHARMACODYNAMIC SAMPLING ...........78 
APPENDIX 3. OPEN LABEL EXTENSION (OLE) .................................................................79 
APPENDIX 4.    OLE SCHEDULE OF ASSESSMENTS ...........................................................83 
 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
 
 
LIST OF TABLES 
Table 1: 
Summary of Pamrevlumab Clinical Studies in DMD ................................................24 
Table 2: 
PK parameters in study FGCL-3019-079 following a single dose .............................29 
Table 3: 
Pamrevlumab (or placebo): Dose, Route, and Administration ...................................40 
Table 4: 
Laboratory Tests .........................................................................................................46 
 
LIST OF FIGURES 
Figure 1: 
FGCL-3019-093 Study Schema .................................................................................33 
 
 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
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 
ECG 
Electrocardiogram 
ECM 
ExtraCellular Matrix 
EDC 
Electronic Data Capture 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
EMT 
Epithelial Mesenchymal Transformation 
 
 
Abbreviation 
Definition 
EOS 
End Of Study 
ET 
Early Termination 
FEV1 
Forced Expiratory Volume at 1 second 
FSGS 
Focal Segmental Glomerulosclerosis 
FVC 
Forced Vital Capacity 
GBCA 
Gadolinium-Based Contrast Agent 
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 
LRP 
Lipoprotein Receptor-related Protein 
LVEF 
Left Ventricular Ejection Fraction 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
LVEF % 
Left Ventricular Ejection Fraction percentage 
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 Elow 
PUL 
Performance of Upper Limb 
RBC 
Red Blood Cell 
RCM 
Random Coefficient Model 
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 
ULN 
Upper Limit of Normal 
WBC 
White Blood Cell 
WHODrug 
World Health Organization Drug 
 
 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
1. 
PROTOCOL SYNOPSIS 
PROTOCOL SYNOPSIS 
Study Title: 
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) 
Protocol Number: 
FGCL-3019-093 
Investigational Product: 
Pamrevlumab (FG-3019) 
Study Phase: 
Phase 3 
Indication: 
Duchenne Muscular Dystrophy 
Number of Subjects 
Planned: 
Approximately 92 
Number of Sites Planned: 
Approximately 55 (Globally) 
OBJECTIVES 
To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with 
systemic corticosteroids in subjects with non-ambulatory Duchenne muscular dystrophy (age 
12 years and older). 
ENDPOINTS 
Primary Endpoint: 
Function assessment: 
Change in the total score of Performance of Upper Limb (PUL) 2.0 version, from baseline to 
Week 52. 
Secondary Endpoints: 
Change in percent predicted forced vital capacity (ppFVC) from baseline to Week 52, 
assessed by spirometry. 
Change in the Grip strength of the hands from baseline to Week 52, assessed by Hand-Held 
Myometry (HHM). Change in Left Ventricular Ejection Fraction percentage (LVEF %) from 
baseline to Week 52, assessed by MRI. 
Change in percent predicted peak expiratory flow (ppPEF) from baseline to Week 52, 
assessed by spirometry. 
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 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
PROTOCOL SYNOPSIS 
• Ulna length measurements for indirect measure of growth velocity (cm/year) for subjects 
under the age of 18 
Exploratory Endpoints 
• Change in the subscores of three regional dimensions (High-level (shoulder), Mid-level 
(elbow), Distal-level (wrist and hand)) of PUL, from baseline to Week 52 
• Change in Duchenne Video Assessment severity percentage from baseline to Week 
52. 
• Change in percent predicted forced expiratory volume at 1 second (FEV1) from 
baseline to Week 52. 
• Analysis of progression of dilated cardiomyopathy (DCM) by genetic analysis . 
Fibrosis/MRI assessments: 
• Changes in fibrosis score of the biceps brachii, from baseline to Week 52, assessed by 
MRI. 
• Changes in Cardiac fibrosis score from baseline to Week 52, assessed by Late 
Gadolinium Enhancement (LGE). 
• Change in Myocardial Circumferential Strain [Global Circumferential Strain (GCS)] 
percentage from baseline to Week 52, assessed by cardiac MRI. 
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 non-ambulatory Duchenne muscular dystrophy, 
aged 12 years and older. 
Approximately 92 male subjects will be randomized at a 1:1 ratio to Arm A (pamrevlumab + 
systemic corticosteroid) or Arm B (placebo+ systemic corticosteroid), respectively. 
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 
Subjects who complete the 52-week study (either arm) may be eligible for rollover into a study 
offering an open-label, extension treatment (OLE) with pamrevlumab + systemic 
corticosteroids. 
Additional points: 
The following assessments will be evaluated by a central reader: pulmonary function tests 
(PFTs) and magnetic resonance imaging (MRI). 
A Data Monitoring Committee (DMC) will be utilized and will be composed of external 
experts. Composition and responsibilities of the DMC will be defined in a separate DMC 
charter. The DMC responsibilities will include review of the safety data. 
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Pamrevlumab 
Protocol FGCL-3019-093 A6 
 
 
 
PROTOCOL SYNOPSIS 
The first three doses of the investigational product (IP) infusion will be administered at a 
healthcare facility/study site. Subsequent IP infusion(s) will be given in a healthcare facility 
or home healthcare may be provided as an option for interested subjects at study sites in 
geographic areas where such service could be feasibly provided. 
An Independent blinded Centralized Imaging Charter will be formed to interpret the MRIs 
mentioned as endpoints in this study.  Standardization is important for all clinically used MRI 
measures, and is essential for the study imaging endpoints, to reduce variability and to ensure 
interpretability of the results. 
STUDY PERIODS 
Screening period: Up to 4 weeks 
Treatment period: 52 weeks (last dose on 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 
Efficacy Assessment Period (EAP): At Week 52 
Open label Extension (Appendix 3): Continued treatment with pamrevlumab 
SUBJECT ELIGIBILITY CRITERIA 
Inclusion Criteria 
Subjects must meet all of the following criteria in order to be eligible for the study: 
Age, Consent, and Contraception 
1. Males at least 12 years of age, non-ambulatory at screening initiation 
2. Written consent by patient and/or legal guardian as per regional/ country and/or 
IRB/IEC requirements 
3. Male subjects with partners of childbearing potential must use contraception during the 
conduct of the study, and for 12 weeks after the last dose of study drug. 
DMD Diagnosis: 
4. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a 
validated genetic test 
Performance criteria: 
5. Brooke Score for Arms and Shoulders ≤5 
6. Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and 
cardiac muscle 
7. Able to perform spirometry 
Pulmonary and Cardiac criteria: 
8. Average (of Screening and Day 0) percent predicted FVC between 45 and 85, inclusive 
9. Left ventricular ejection fraction ≥50% as determined by local cardiac MRI read at 
screening or within 3 months prior to randomization (Day 0) 
10. If subjects have a history of cardiomyopathy, then subject must be on a stable dose of 
cardiomyopathy/ heart failure medications (e.g., angiotensin converting enzyme 
inhibitors, aldosterone receptors blockers, angiotensin- receptor blockers, and beta-
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PROTOCOL SYNOPSIS 
blockers) for at least 1 month prior to screening.  If subjects have no diagnosis of 
cardiomyopathy, then no dose of cardiomyopathy/heart failure medication is required 
for eligibility. 
11. 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. 
Vaccination: 
12. Agreement to receive annual influenza vaccinations during the course of the study. 
Laboratory criteria: 
13. Adequate renal function: cystatin C ≤1.4 mg/L 
14. 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. 
15. 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 
Exclusion Criteria 
Subjects must not meet any of the following criteria in order to be eligible: 
General criteria: 
1. Previous exposure to pamrevlumab 
2. BMI ≥40 kg/m2 or weight >117 kg 
3. 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 
c. hypersensitivity reaction to Gadolinium-based Contrast Agents (GBCA) 
required for MRI acquisition 
4. 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 
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screening, whichever is longer, with the exception of the systemic corticosteroids, 
including deflazacort 
Cardiac, Renal,  and Pulmonary assessments: 
5. 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 
6. Arrhythmia requiring anti-arrhythmic therapy 
7. Requires ≥16 hours continuous ventilation 
8. Hospitalization due to respiratory failure within the 8 weeks prior to screening 
9. 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 
Clinical judgments: 
10. 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 or psychiatric conditions 
 
STUDY TREATMENT 
Dose 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 study. 
Systemic Corticosteroids: Administered orally. 
 
Other Important Information: 
Subjects will receive full supportive care as required by their clinical condition. 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. Excluded concomitant medications include any approved 
DMD therapy (e.g. eteplirsen (exondys 51), ataluren, golodirsen (vyondys 53), casimersen 
(amondys 45)) and any investigational agent, including those that receive marketing 
authorization during this trial, with the exception of systemic corticosteroids, and deflazacort. 
Study drug should not be administered to subjects with a history of allergic or anaphylactic 
reaction to human, humanized, or chimeric monoclonal antibodies. 
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STATISTICAL METHODS 
Sample Size Calculations: 
This study is planned to enroll approximately 92 subjects with a 1:1 randomization ratio of 
assigning to pamrevlumab and placebo, respectively. With PUL version 2.0, the sample size 
of approximately 92 subjects is needed to detect a treatment difference of 2.0 between 
treatment arms in change from baseline in the total score of PUL at Week 52, assuming a 
standard deviation of 2.9 with a 90% power, based on a two-sided two-sample t-test at the 
alpha level of 0.05. 
Statistical Analysis Methods: 
The primary endpoint, change in the total score of Performance of Upper Limb [(PUL) 2.0 
version], from baseline to Week 52 will be analyzed using a random coefficient model (RCM) 
with treatment, visit, visit-by-treatment interaction, and baseline total score of Performance of 
Upper Limb value as fixed effects; the intercept and linear slope of visit as random effects. 
The primary analysis will be based on observed data from subjects in the Intent to Treat (ITT) 
population. 
As sensitivity analysis, the analysis of covariance model (ANCOVA) with Multiple 
Imputations (ANCOVA –MI) will be also applied. The model will include treatment and 
baseline total score of PUL value. The primary analysis will be based on the ITT population. 
The change from baseline to Week 52 in ppFVC will be analyzed using a random coefficient 
model with treatment, visit, visit-by-treatment interaction, and baseline ppFVC as fixed 
effects; the intercept and linear slope of visit as random effects. The analysis will be based on 
observed data from subjects in the ITT population. 
The change from baseline to Week 52 ppPEF will be analyzed using a random coefficient 
model with treatment, visit, visit-by-treatment interaction, and baseline ppPEF as fixed effects; 
the intercept and linear slope of visit as random effects. The analysis will be based on 
observed data from subjects in the ITT population. 
For other secondary endpoints, 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. 
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 
by treatment arm. Additionally, hypersensitivity/anaphylactic reactions will be monitored and 
the impact of immunogenicity will be assessed, during the entire course of the trial. 
 
This study will be conducted in accordance with the guidelines of Good Clinical Practice 
(GCP) and the applicable regulatory requirement(s), including the archiving of essential 
documents 
 
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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.   
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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). 
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, 
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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- 
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 fibrodegenerative 
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. 
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Overall, pamrevlumab has been well tolerated. TThe 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. 
2.6. 
Rationale and Risk/Benefit for Pamrevlumab in Duchenne Muscular 
Dystrophy 
Table 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 
92  
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 
2.6.1. 
Rationale 
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. 
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2.6.2. 
Primary endpoint: Performance of the upper limb 
Upper limb function is identified as a key priority for DMD patients’ quality of life (Bergsma, 
2015). The Performance of the Upper Limb (PUL) assessment was developed specifically to 
evaluate the wide ranging upper limb function in ambulant and non-ambulant patients with DMD 
(Mayhew et al, 2013). The PUL tool has been validated to provide evidence of functional 
progression of distal to proximal upper limb function evolution over time (Gandolla, 2020), ideal 
for clinical trial use. 
2.6.3. 
Secondary endpoint: Forced vital capacity 
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 
(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) 
2.6.4. 
Secondary Endpoint: 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. 
2.6.5. 
Secondary endpoint: Grip Strength assessed by Hand-Held Myometry (HHM) 
Preserving upper limb strength is very important in non-ambulatory DMD patients because it 
provides functional independence. Hand-Held Myometry (HHM) is being used in Study 079 
tomeasure distal upper arm strength (grip and pinch strength), and it has shown very good 
reliability and feasibility in non-ambulatory DMD patients (Connolly 2015). A one-year follow 
up study in non-ambulatory DMD patients showed a mean decline in grip strength of (-3.0 
newton in non-dominant arm, - 2.7 newton dominant arm) and in pinch strength (-2.2 newton in 
non-dominant arm, -1.7 newton in dominant arm) (Seferian 2015). In a more recent prospective 
natural history study (Ricotti 2019), the mean annual change from baseline (dominant arm) in 
Myogrip absolute value was -3.82 newton, and in Myopinch absolute value was -0.78 newton. 
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2.6.6. 
Secondary endpoint: Left ventricular ejection fraction percentage (LVEF %) 
Patients with DMD, have progressive cardiac muscle dysfunction, which is the leading cause of 
mortality. Cardiac magnetic resonance imaging (cardiac MRI), was used to assess the left 
ventricular ejection fraction percentage (LVEF%) in Study 079. Care considerations for DMD 
(Birnkrant 2018) state that pharmacological therapy should be initiated with the onset of heart 
failure symptoms or when abnormalities such as depressed LVEF%, abnormal chamber 
dimensions, or the presence of myocardial fibrosis are noted on imaging studies (CMR or 
echocardiogram). Additionally, placement of an implantable cardioverter defibrillator is advised 
for patients with an ejection fraction of less than 35% (Epstein 2008). Based on data tracking the 
natural disease history, a decrease in LVEF of 0.82% per year of age (95% CI 0.94 to 0.70; p < 
0.0001) has been observed. (McDonald 2018). 
2.6.7. 
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).Cardiac 
fibrosis score/ Late gadolinium enhancement (LGE) 
Late Gadolinium Enhancement (LGE) is a strong marker for the progression of left ventricular 
systolic dysfunction in DMD patients. Improvements in the cardiac function observed above are 
further supported by the reduction in cardiac fibrosis assessed by LGE, which is a strong marker 
for the progression of left ventricular systolic dysfunction in DMD patients.  
Additionally, cardiac fibrosis, assessed by mass of late gadolinium enhancement (MLGE) 
showed a correlation between improvement in LVEF% and reduction in cardiac fibrosis, 
mentioned in Tandon, et al 2015 (Tandon, 2015). 
2.6.8. 
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, oedema, and fat infiltration present in 
the affected muscle (Magrath 2018). 
Overall, the results from the completed phase 2 main study in non-ambulatory DMD subjects 
show that pamrevlumab may have a beneficial effect on several clinically meaningful 
parametersaffecting 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-
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benefit ratio remains favorable. For more information please reference the current 
Investigator’s Brochure. 
2.7. 
Dose Rationale 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 
aresummarized below. 
2.7.1. 
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/m2, compared to 29 kg/m2 in other cohorts). 
2.7.2. 
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 
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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. 
2.7.3. 
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 
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. 
2.7.4. 
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: 
• Cmin and Cmax values increased with increasing dose. Analysis of Cmax indicated 
that increases were dose proportional. 
• Cmin and Cmax values generally increased with repeated dosing, which is consistent with 
the dosing regimens and t½ of pamrevlumab. 
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• Pamrevlumab exposure (based on estimated AUC values) generally increased with 
increasing dose. 
• Overall, Cmin and Cmax values were comparable to those at similar doses in previous 
studies. 
• On Day 1, Tmax was 3 hours from the start of dosing and 1 hour from the end of the 
infusion. On Day 43, Tmax was 2 hours from the start of dosing and 1 hour from 
the end of the infusion. 
• After the first dose, the estimated median t½ increased 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 t1/2 increased from 2.6 days for the 3 mg/kg dose to 6.6–9.0 days 
for doses ≥10 mg/kg. 
• Estimated t½ 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 and 7.29 days, respectively). 
2.7.5. 
Single 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 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 
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 
 
Tmax 
Cmax 
AUCt 
AUC0-∞ 
t1/2 
CL 
Vz 
Vss 
(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 
2.8. 
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 
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subjects with DMD, 107 subjects with DN, 2 pediatric subjects with FSGS, and 43 healthy 
subjects. For additionalinformation on the safety of pamrevlumab in the completed DMD study 
(079) and other indications, please refer to the current versionof the Investigator’s Brochure. 
 
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3. 
OBJECTIVES AND ENDPOINTS 
3.1. 
Objective 
The overall objective of this trial is to evaluate the efficacy and safety of pamrevlumab versus 
placebo in combination with systemic corticosteroids in subjects with Duchenne muscular 
dystrophy (non-ambulatory, age 12 years and older). 
3.1.1. 
Endpoints 
3.1.1.1. 
Primary Endpoint 
Function assessment: 
• Change in the total score of Performance of Upper Limb [(PUL) 2.0 version], from 
baseline to Week 52. 
3.1.1.2. 
Secondary Endpoints 
• Change in percent predicted forced vital capacity (ppFVC) from baseline to Week 52, 
assessed by spirometry. 
• Change in the Grip strength of the hands from baseline to Week 52, assessed by Hand 
Held Myometry (HHM). 
• Change in Left Ventricular Ejection Fraction percentage (LVEF %) from baseline to 
Week 52, assessed by MRI. 
• Change in percent predicted peak expiratory flow (ppPEF) from baseline to Week 
52, assessed by spirometry. 
3.1.1.3. 
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 
Ulna length measurements for indirect measure of growth velocity (cm/year) for subjects under 
the age of 18. 
3.1.1.4. 
Exploratory Endpoints 
• Change in the subscores of three regional dimensions (High-level (shoulder), Mid-
level (elbow), Distal-level (wrist and hand)) of PUL, from baseline to Week 52 
• Change in Duchenne Video Assessment severity percentage from baseline to Week 
52. 
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• Change in percent predicted forced expiratory volume at 1 second (FEV1) from 
baseline to Week 52. 
• Analysis of progression of dilated cardiomyopathy (DCM) by genetic analysis. 
Fibrosis/MRI assessments: 
• Changes in fibrosis score of the biceps brachii, from baseline to Week 52, assessed by 
MRI. 
• Changes in Cardiac fibrosis score from baseline to Week 52, assessed by Late 
Gadolinium Enhancement (LGE). 
• Change in Myocardial Circumferential Strain [Global Circumferential Strain (GCS)] 
percentage from baseline to Week 52, assessed by cardiac MRI. 
3.1.1.5. 
Pharmacokinetics/pharmacodynamics (PK/PD) assessment 
• Population PK/PD analysis. 
3.2. 
Overall Study Design 
This is a Phase 3, randomized, double-blind, placebo-controlled multi-center trial to evaluate the 
efficacy and safety of pamrevlumab in subjects with DMD over a 52-week period. 
Approximately 92 subjects will be enrolled in this trial, globally. 
Subjects must be fully informed of the potential benefits of approved products and make an 
informed decision that they prefer to participate in a clinical trial in which they could be 
randomized to placebo. 
Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab 
or placebo. 
This trial 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. 
In the screening period, subjects will be evaluated per the protocol inclusion/exclusion criteria to 
determine eligibility for participation in this trial. 
During the treatment period, each subject will receive pamrevlumab or placebo at 35 mg/kg 
every 2 weeks for up to 52 weeks. 
Subjects who complete the study 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. 
A schematic overview of the study is provided in Figure 1. A detailed overview of assessments 
and the timing of assessments is provided in Appendix 1. 
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3.2.1. 
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 
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) after the last dose and a 
finalsafety follow-up phone call 60 days (+ 3 Days) after the last infusion. If a subject 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 Section 
4.4 for procedures related to the ET. 
Subjects who complete the study may be eligible for rollover into an open-label, extension study 
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. 
Figure 1: 
FGCL-3019-093 Study Schema 
 
 
Abbreviations: EOS= End of Study, ET=Early Termination 
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. 
3.2.2. 
Placebo Control Group 
In order to evaluate the effect of treatment with pamrevlumab on the endpoints described in 
Section 3.1.1  approximately 50% of subjects will be randomized to placebo treatment. 
For DMD subjects, one of the only current FDA approved treatment options is systemic 
corticosteroids, which is available to them as part of this protocol. Therefore, placebo control, 
given with systemic corticosteroids, is appropriate and ethical. Additionally, all study subjects, 
including those randomized to placebo and who complete the study may be offered crossover to 
the active arm in the OLE. 
3.3. 
Subject ID Assignment 
Subjects that sign consent will be assigned an 8 digit Subject ID number consisting of a four 
digit site number and a 4 digits Subject ID starting with 1xxx. Subject numbering will be 
assigned sequentially as subjects are recruited/screened (e.g., 1001, 1002, and 1003, etc.). 
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3.4. 
Randomization and Treatment Assignment 
3.4.1. 
Randomization 
Approximately 92 subjects will be randomized 1:1 to receive either pamrevlumab or placebo, 
resulting in approximately 46 subjects in treatment arm A and 46 subjects in treatment arm B. 
Randomization schedules will be prospectively prepared.  Automated randomization and 
treatment assignments will be performed by an Interactive Response System (IXRS or IRT). 
3.4.2. 
Treatment Assignment 
Subjects will be randomized 1:1 to one of two treatment arms: 
 
Arm A 
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 
 
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 subjects 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, and Contraception 
1. Males at least 12 years of age, non-ambulatory at screening initiation 
2. Written consent by patient and/or legal guardian as per regional/ country and/or IRB/IEC 
requirements 
3. Male subjects with partners of childbearing potential must use contraception during the 
conduct of the study, and for 12 weeks after the last dose of study drug. 
DMD Diagnosis: 
4. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a 
validated genetic test 
Performance criteria: 
5. Brooke Score for Arms and Shoulders ≤5 
6. Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and 
cardiac muscle 
7. Able to perform spirometry 
Pulmonary and Cardiac criteria: 
8. Average (of Screening and Day 0) percent predicted FVC between 45 and 85, inclusive 
9. Left ventricular ejection fraction ≥50% as determined by local cardiac MRI read at 
screening or within 3 months prior to randomization (Day 0) 
10. If subjects have a history of cardiomyopathy, then subject must be on a stable dose of 
cardiomyopathy/ heart failure medications (e.g., angiotensin converting enzyme 
inhibitors, aldosterone receptors blockers, angiotensin- receptor blockers, and beta-
blockers) for at least 1 month prior to screening.  If subjects have no diagnosis of 
cardiomyopathy, then no dose of cardiomyopathy/heart failure medication is required for 
eligibility. 
11. 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. 
Vaccination: 
12. Agreement to receive annual influenza vaccinations during the course of the study. 
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Laboratory criteria: 
13. Adequate renal function: cystatin C ≤1.4 mg/L 
14. 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 
e. (P) levels are within a clinically accepted range for DMD patients. 
15. Adequate hepatic function: 
 
 
a. No history or evidence of liver disease 
 
b. Gamma glutamyl transferase (GGT) ≤3x upper limit of 
 
c. Total bilirubin ≤1.5xULN 
4.2. 
Subject Exclusion Criteria 
Subjects will be ineligible for and excluded from this trial if any of the following apply: 
General criteria: 
1. Previous exposure to pamrevlumab 
2. BMI ≥40 kg/m2 or weight >117 kg 
3. 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 
c. hypersensitivity reaction to Gadolinium-based Contrast Agents (GBCA) required for 
MRI acquisition 
4. 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 
Cardiac, Renal, and Pulmonary assessment: 
5. 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 
6. Arrhythmia requiring anti-arrhythmic therapy 
7. Requires ≥16 hours continuous ventilation 
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8. Hospitalization due to respiratory failure within the 8 weeks prior to screening 
9. 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 
Clinical judgments: 
10. 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 or psychiatric conditions which could confound 
efficacy assessment and/or safety assessment. 
4.3. 
Subject Withdrawal Criteria 
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.    
Mandatory reasons for withdrawing the subject from the study include the following: 
• Any safety concern in the Investigator’s opinion, that precludes further study 
participation 
− 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) 
4.4. 
Subject Withdrawal Procedure 
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 a 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, PFTs and MFTs must be conducted.  MRIs do not have to 
be repeated if the last one was performed within 4 weeks of this visit. 
4.5. 
Replacement of Study Subjects 
All randomized subjects will be included in the study. Subjects who discontinued the study early 
will not be replaced. 
4.6. 
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): 
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• Successful completion of the study at the investigational site 
• The required number of subjects for the study has been recruited 
• Failure of the Investigator to comply with the protocol, GCP guidelines or local 
requirements 
• Safety concerns 
• Inadequate recruitment of subjects by the Investigator
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5. 
TREATMENT OF SUBJECTS 
5.1. 
Study Treatment 
5.1.1. 
Pamrevlumab or Placebo 
Pamrevlumab is a fully human IgG1 kappa monoclonal antibody that binds to CTGF and is 
formulated as solution for administration by IV infusion.  Peripheral or central venous access 
may be utilized at the discretion of the investigator. 
Matching placebo is formulated as solution to be administered in a manner that is identical to 
pamrevlumab infusion. 
5.1.1.1. 
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. 
5.1.1.2. 
Study Drug Packaging and Labeling 
Labels will be prepared and will comply with Good Manufacturing Practice requirements for 
labelling and local regulatory guidelines. 
5.1.1.3. 
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 IP Manual. 
5.1.2. 
Study Drug Preparation 
Pamrevlumab or placebo is infused undiluted after pooling the contents of the calculated number 
of vials in an empty infusion bag (total volume of fluid must not exceed 410 mL) according to 
the Dose Preparation Instructions in the Investigational Product (IP) Manual. 
Pamrevlumab and placebo solutions for infusion must be stored refrigerated (2˚C to 8˚C) and 
administered within 48 hours of preparation or 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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5.1.3. 
Study Drug (Investigational Product) 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 as soon as possible 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. 
IP 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 matching 
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 IP 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. Subjects who experience an infusion reaction will not be allowed to participate in Home 
Health Care (HHC). If the Investigator wishes to use premedication, (e.g., antihistamines, 
nonsteroidal anti-inflammatory drugs (NSAIDs)) for a subsequent infusion should be discussed 
with the sponsor 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. 
Study Drug will be administered at a hospital or ambulatory setting with adequate facilities for 
managing medical emergencies. Medications for the treatment of acute reactions, including 
anaphylaxis, must be available to study site staff for immediate use. Medications for the 
treatment of acute reactions, including anaphylaxis, will be maintained at the subject’s home for 
access by 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. 
The Sponsor may consider the use of properly trained home health care staff to administer the 
infusions of study drugs at the subject’s home and corresponding study assessments during the 
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conduct of the study (after the completion of three infusions without safety concerns), consistent 
with institutional regulations and policies (see Section 5.1.4 for details). 
The following procedures must be performed prior to each infusion: 
• Vital signs (sitting blood pressure [BP], pulse, respiration, and temperature) within 30 
minutes before starting the infusion 
• Query subject and assess TEAEs 
• Record concomitant medications 
The following procedures must be performed after each infusion: 
• Vital signs (sitting blood pressure [BP], pulse, respiration, and temperature) within 30 
minutes after completion of the infusion 
• Query subject and assess TEAEs 
5.1.4. 
Home Health Care 
The Sponsor may consider the use of properly trained home health care staff in specific 
regions/countries depending on local acceptance and adoption of home infusions 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 in study clinic without safety 
concerns), consistent with institutional regulations and policies. Home Health Care is optional 
and the decision to utilize is driven by a combination of the study site, the availability of 
qualified service, and Sponsor decision on overall feasibility. Subjects who experience an 
infusion reaction will not be allowed to participate in HHC. Following any adverse reaction at a 
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.  Medications for the treatment of acute 
reactions, including anaphylaxis are required to be present in the patient’s home for all IMP 
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. 
HHC support will only be on weeks where other assessments are not being completed. PI 
maintains overall responsibility for patient care and 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. 
5.1.5. 
Missed Dose 
Every attempt should be made to complete all study visits within window as outlined in the 
Schedule of Assessment (SOA) (Appendix 1). 
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 sponsor 
Medical Monitor should be notified. The reason for missed doses must be documented in the 
subject’s clinical record. 
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Refer to the case report form (CRF) completion guidelines in the Study Reference Manual for 
additional information on CRF completion requirements for missed visits. 
5.1.6. 
Study Drug 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 drug 
accountability and reconciliation for all study drug received at the site prior to approving study 
drug return/destruction. Upon completion of accountability/reconciliation or upon completion of 
the study or termination of the investigational site, all unused IP and all study drug that was not 
dispensed will be shipped to a destruction site designated by the Sponsor (or designee) for 
destruction. IV bags used to infuse study drug can be disposed of per institutional policy. Please 
refer to the IP Manual for additional information on study drug materials, management and 
accountability. 
5.1.7. 
Treatment Compliance 
All treatments are administered at the investigational site by qualified personnel and documented 
in the corresponding case report form (CRF). 
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, the Sponsor 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 the sponsor 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 vaccinations 
while on study should be entered into the Concomitant Medication CRF.   
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5.2.2. 
Prohibited Concomitant Medications 
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) 
• casimersen (AMONDYS 45) 
Questions about concomitant medications should be discussed with the Sponsor Medical 
Monitor or designee. Patients who are on any approved therapy for DMD should not discontinue 
the therapy to be eligible for the 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. 
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 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. 
Therefore, male subjects who have partners with reproductive potential are required to use 
contraception during the conduct of the study and for 12 weeks 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 and until the end of relevant systemic exposure in the partner of the 
woman of child bearing potential. Sexual abstinence is considered a highly effective method only 
if defined as refraining from heterosexual intercourse during the entire period of risk associated 
with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the clinical trial and the preferred and usual lifestyle of the subject. The package 
insert regarding reproductive risks associated with the use of any corticosteroids used in this 
study should be evaluated and reviewed with the subject. 
SWITZERLAND ONLY: Sexual abstinence is not considered an effective contraception method 
and local contraception regulatory guidelines must be followed accordingly. 
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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 may be adjusted and conducted at the 
discretion of the Investigator, in accordance with the site’s rules and recommendations, and 
using all necessary precautions. If a visit has to be done remotely, it can be conducted with any 
technology available to the site and study subjects, such as via tele-health visits, phone calls, etc. 
6.1.1. 
Screening Period 
All screening procedures must be performed within 28 days. 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 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, which depends on the timing of rescreening. 
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 must also agree to receive annual influenza vaccinations during 
the course of the study as needed. 
6.1.2. 
Randomized Treatment Period 
The study procedures and assessments are presented for the Randomized Treatment phase in 
Appendix 1 and Appendix 3 for the OLE. 
The Randomized Treatment Phase begins on Day 0 (first infusion of IP) 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. 
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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. 
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 the Sponsor 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 
unless there is an AE/SAE/intercurrent illness, in which case, study treatment may be withheld/
interrupted, resulting in a “missed” visit. Refer to Section 5.1.5 for additional details. For missed 
visits without an AE/SAE/intercurrent illness, 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 PFTs or MFTs adequately on a scheduled visit should repeat PFT or MFT assessment as 
soon as possible, or at minimum ensure to complete PFT or MFT assessment at the next 
scheduled on-site visit.   If the subject is unable to perform PFTs or MFTs at week 52 then the 
subject must have an unscheduled visit at the nearest possible date to perform PFTs or MFTs. 
6.2. 
Assessments 
Refer to the SOA (Appendix 1) for the main study, and Appendix 3 for the OLE for details 
regarding the timing and frequency of study assessments.  Laboratory evaluations, muscle 
function tests and spirometry assessments should be performed prior to infusions. 
6.2.1. 
Vital Signs (including Weight) 
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 using any standard method and captured as °F or °C
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Weight is collected during screening, and every 12 weeks (or within 14 days prior) after Day 0. 
Height is collected as ulna length measurement by respiratory technician only, during PFT visits.  
For subjects that enter the study at age 18 or turn 18 during the study, the last recorded ulna 
length/height will be used for the remainder of the study. 
6.2.2. 
Physical Exam 
A full physical exam is required at screening, throughout the treatment period, and at EOS and 
ET.  Refer to the SOA (Appendix 1) for details. 
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 Laboratory Evaluations 
The following labs will be evaluated by a central laboratory in accordance with the SOA 
(Appendix 1): 
The total amount of blood to be drawn for routine central laboratory assessments is in      
Appendix 2.  The max total for any blood draw visit is about 1.8 tablespoons (26ml/visit). An 
additional 1.4 teaspoons (20 ml) will be drawn in the event of an immunogenic reaction (see 
Section 6.2.3.2.3 for more detail).  
Local guidance and regulations on total blood volume to be drawn takes precedence over general 
recommendations. 
Glomerular Filtration Rate (GFR) is calculated and resulted by the central lab contracted by the 
Sponsor for Exclusion Criteria 5c. For subjects 18 years old and under, the “Creatinine – 
Cystatin C based CKiD equation (Schwartz 2012)” is used.   For subjects 19 years old and 
above, the “CKD-EPI cystatin C equation (Levey 2009)” 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.  
Table 4: 
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 
Lymphocytes 
ALT 
Monocytes 
AST 
Neutrophils 
Bilirubin, total 
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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 
Central lab results obtained during the screening period will be used to determine subject 
eligibility for participation in the trial. Central lab results will be reviewed by the investigator 
for clinical significance and to determine appropriate reporting of adverse events (see Section 
7.3).  A Central Laboratory Manual with instructions on specimen collection, processing, storing, 
and shipping to the central laboratory will be provided to all participating sites. 
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 conducted prior to MRI will not 
be captured in the clinical database. 
NOTE: Local laboratory assessments may also be used in case of Central Laboratory supply 
shortages or shipment delays. If local laboratory assessments are used instead of central labs, 
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 specialty labs collected at a local laboratory: 
− HAHA and HAHA-NA samples should be collected according to the schedule of 
assessments in Appendix 2 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 at a later time 
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− 
Other specialty samples (PK and Genomics) will not be required if local labs are 
being used 
6.2.3.2. 
Pharmacokinetics (PK) and Specialty Labs 
Additional samples will be collected to evaluate PK, HAHA, HAHA-NA, tryptase, and 
genomics in accordance with the SOAs in Appendix 1 and Appendix 2. The central laboratory 
will manage the storage of these samples while analysis will be performed at a specialty lab(s). 
6.2.3.2.1. Pharmacokinetics 
An optional PK assessment will be performed in  consenting subjects at timepoints specified in 
Schedule of Assessments. . For subjects that reconsent under the main study of this protocol, PK 
assessments will continue to be optional except in the case of immunogenic reaction (see Section 
6.2.3.2.3 for more detail).  Plasma samples will be collected for estimates of PK parameters 
using population PK and exposure- response analysis, if possible, according to the SOAs in 
Appendix 1 and Appendix 2. A specialty laboratory will measure plasma pamrevlumab levels 
using a validated assay. For the population PK analysis, it is critical to accurately record the 
dosing time and date in addition to the sampling collection time and date. Both pre-dose and 
post-dose samples are required for PK 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. 
6.2.3.2.2. Human Anti-Human Antibodies (HAHA) 
Plasma samples will be collected for evaluation of human anti-human antibodies (HAHA), 
specific to the impact of neutralizing anti-drug antibodies (HAHA-NA) and the impact on 
immunogenicity, in all subjects according to the SOAs in Appendix 1 and Appendix 2. A 
specialty laboratory will measure HAHA titers using a validated assay. 
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. 
6.2.3.2.3. Immunogenic Reactions 
Any immunogenic reactions, including drug-related hypersensitivity or anaphylaxis, should have 
PK, HAHA, HAHA-NA and tryptase drawn within 24 hours of immunogenic reaction 
(anaphylactic episode). (A window of “within 24 hours of infusion” could be at any point 
following the reaction such as 30 minutes post-reaction but not to exceed 24 hours following 
reaction).   This includes timepoints in which PK, HAHA, and HAHA-NA were drawn prior to 
the reaction as well.  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.  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.  See 
Appendix 2 for more detail.   
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6.2.3.2.4. DNA for Genetic Analysis 
A whole blood sample will be collected in a PAXgene blood DNA tube for DNA analysis on 
Day 0 before dosing for all subjects who agree to DNA analysis. This testing is optional, 
requires specific consent by participating subjects and subjects may refuse DNA testing. In 
the event that a subject later agrees to genetc testing, a blood sample may be collected as an 
unscheduled lab draw.  Only tests for genetic loci associated with dilated cardiomyopathy 
(DCM) will be performed and all samples will be destroyed after testing is completed. 
6.2.4. 
Muscle Function Test (MFT) 
Performance of Upper Limb (PUL) and grip strength tests will be performed during the course of 
the study. PUL 2.0 Kits will be provided. The grip test should be performed using a 
microFET® Digital Hand GRIP Dynamometer (unless specified otherwise in limited countries). 
The same equipment should be used for each subject, and for the duration of the study. MFTs 
are to be completed by a dedicated and trained staff member(s).  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 QC of the MFT assessments will be completed by 
external vendor ATOM at Screening, Day 0, Week 52, and additional visits as needed, and the 
videos will be evaluated by an independent reviewer to confirm the local clinical evaluator is 
consistently administering the MFT.  Data will also be assessed by independent reviewers on an 
ongoing basis. 
6.2.5. 
Pulmonary Function Test (PFT) 
Standardized PFTs including ppFVC, ppPEF, , FEV1 will be collected for consistency during the 
course of the study.  The central PFT vendor will provide the SpiroSphere® to conduct these 
assessments.  PFTs will be completed by dedicated trained staff.  All staff performing PFTs must 
pass a proficiency test to administer the test.  Data will be reviewed by independent reviewers at 
the central PFT vendor to validate the integrity of the data. Within a PFT session, eight attempts 
may be made. Only sessions with a Best Test Read (BTR) grade of Borderline or Acceptable are 
considered valid. The session may be repeated up to three times during the screening window. 
The Day 0 PFT session may also be repeated up to three times. If the test cannot be performed, 
or the test produces Unacceptable grade results according to the central reader during a follow-up 
visit, the test should be performed at the next scheduled on-site visit. Valid PFT results 
(Acceptable or Borderline Acceptable) must be obtained at Screening and Baseline for eligibility 
prior to randomization.  If sessions are repeated, the last session conducted for screening, and the 
last session conducted for Day 0 supersede all others and are used to determine the average for 
baseline.  The inclusion criteria requires that the average percent predicted FVC be between 45 
and 85, inclusively and values may be rounded such that values between 44.5 and 85.4 are also 
acceptable. 
6.2.6. 
Magnetic Resonance Imaging (MRI) 
MRI (cardiac and muscle) assessments will be performed to evaluate fibrosis and to determine 
any changes in fibrosis score from baseline to Week 52. 
• Cardiac MRIs are assessed locally at Screening for eligibility before being submitted 
to the central imaging vendor 
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• A centralized image interpretation process will be formed and 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. 
• An Independent blinded Centralized Imaging Charter will be formed to interpret the 
MRIs.  Standardization is important for the clinically used MRI measures, and is 
essential for the study imaging endpoints, 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”. 
6.2.7. 
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 DVA vendor is the organization that 
developed the DVA and 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 kit (materials provided to each 
subject and caregiver) 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. 
Subjects will be assigned movement tasks based on functional branching questions prior to 
Baseline data capture and split into two functional groups based on their Brooke score as noted 
below.  Subjects will remain in the same subgroup (Group A or B) throughout the duration of the 
study. 
Group A: Early Non-Ambulatory 
Subjects (Brooke Score 1-3) 
Group B: Late Non-Ambulatory 
Subjects (Brooke Score 4-5) 
Raise Hands Above Head (Front View 
and Side View) 
Take a T-Shirt Off and Put it Back On 
Eat 10 Bites 
Roll Over in Bed 
Sit Up (Shift Weight) in Bed 
Caregiver Choice 
New Ability 
Eat 10 Bites 
Putting Arms on Armrest 
Reach Across Table to Grab Cell 
Phone 
Sit up (shift Weight) in Bed 
Caregiver Choice 
New Ability 
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The specific movement activities are detailed in the Caregiver Manual. Caregivers will be 
provided with study supplies, including painter’s tape, tape measure, and a bed wedge. 
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 that the subject is struggling with, and 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. 
DVA vendor services and their mobile application will not be used in these countries. 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 from investigators are the critical building blocks to the development 
of the safety profile of the IP. Subjects will be asked non-leading questions in general terms to 
determine the occurrence of AEs, according to the schedule outlined in Appendix 1. In addition, 
all AEs reported spontaneously during the course of the study will be recorded. The investigator 
is responsible for ensuring that any adverse events observed by the investigator or reported by 
the subject as defined in the study protocol are recorded in the subject’s medical record. The 
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 adverse event 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, 
• A life-threatening AEs (i.e., if in the view of the investigator or sponsor, the subject 
was at immediate risk of death at the time of the event). Life-threatening does not 
refer to an event which hypothetically might have caused death if it were more 
severe, 
• Inpatient hospitalization or prolongation of existing hospitalization, 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, 
• A congenital anomaly or birth defect, or 
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• Is considered a medically important event not meeting the above criteria, but which 
may jeopardize a subject or may require medical or surgical intervention to prevent 
one of the other criteria listed in this definition. Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or 
at home, and blood dyscrasias or convulsions that do not result in inpatient 
hospitalization. 
Please note that death is an outcome, not an event; the primary cause of death would be the 
adverse event. 
Surgical procedures, per se, are not SAEs. The condition requiring the surgical procedure, 
however, may be a SAE. 
Scheduled or pre-planned hospitalization or prolongation of a hospitalization due to standard of 
care assessments and procedures (including elective procedures) do not warrant reporting as 
adverse events unless resulting observations are deemed by the Investigator to meet the 
definition of an adverse event. 
7.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events 
7.3.1. 
Adverse Event Reporting Period 
The safety reporting period begins after the subject has signed the informed consent and ends 60 
days after the last dose of IP.  SAEs  that occur after signing consent but before first dose must be 
reported, while all AEs and SAEs be reported thereafter first dose and through 60 days after the 
last dose of pamrevlumab/placebo are recorded. 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 a Duchenne Video Assessment video after the 
first infusion of pamrevlumab or placebo, the 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 
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require treatment or adjustment in current therapy are considered adverse events. Where 
applicable, clinical sequelae (not the laboratory abnormality) are to be recorded as the adverse 
event. The investigator is expected to follow reported adverse events until stabilization or 
reversibility.The following attributes must be assigned to each AE: 
• Description (Investigator’s verbatim term describing the event) 
• Dates of onset and resolution 
• Severity 
• Relationship to study drug 
• Outcome 
• Action taken regarding study drug 
• Other treatment required 
• Determination of “seriousness” 
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 
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 
serious adverse events 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 serious adverse events 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 end of 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 according to 
the guidance in Section 7.3.4. 
If the death occurred within the AE collection and reporting period (signed ICF to 60 days after 
last dose) and meets the reporting criteria, the investigator must submit the SAE Report Form in 
the same manner as described above in Section 7.3.5. If the investigator becomes aware of a 
death occurring after the AE reporting period and considers it related to pamrevlumab, it will be 
reported as an SAE. 
7.3.6. 
Pregnancies: Reporting and Follow-up of 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. The outcome of the 
pregnancy must be reported by the investigator on a Pregnancy Outcome Report Form, which 
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should be sent to the Sponsor and/or its designated safety vendor within 24 hours of the 
investigator becoming aware of the outcome. 
Pregnancy itself is not an AE unless there is a suspicion that the investigational product under 
study may have interfered with the effectiveness of a contraceptive medication. Pregnancies are 
followed up to outcome even if the subject was discontinued from the study. Congenital 
abnormalities/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs. 
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 (Sampson, 2006). 
Anaphylaxis is highly likely when the following criteria is fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue- 
uvula). 
And at least one of the following criteria: 
a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for 
that patient (minutes to several hours): 
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen 
lips-tongue-uvula) 
b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced 
PEF, hypoxemia) 
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d. Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
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a. Systolic BP of less than 90 mm Hg or greater than 30% decrease from that person's 
baseline 
7.3.9. 
Safety Monitoring 
Safety will be assessed throughout the study. A medically complete baseline profile of each 
subject will be established through medical history, a complete physical examination including 
vital signs and laboratory tests. During the course of the study, vital signs and laboratory tests 
will be performed at frequent intervals as described in Appendix 1 and Appendix 2. Any 
medically significant changes from baseline will be monitored throughout the study and 
appropriate interventions will be taken accordingly. Safety and tolerability will be monitored 
closely by 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 SAE Reporting Instructions for more detail. 
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 
This study is planned to enroll approximately 92 subjects with a 1:1 randomization ratio of 
assigning to pamrevlumab and placebo, respectively. With PUL version 2.0, the sample size of 
approximately 92 subjects is needed to detect a treatment difference of 2.0 between treatment 
arms in change from baseline in the total score of PUL at Week 52, assuming a standard 
deviation of 2.9 with a 90% power, based on a two-sided two-sample t-test at the alpha level of 
0.05. 
8.2. 
Analysis Populations 
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.  The secondary endpoints will be tested sequentially at the 0.05 significance 
level; once an endpoint pass the 0.05 significance test level then the testing will move to the next 
secondary endpoint. 
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. 
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 
The analyses of the efficacy endpoints will be based on subjects in the ITT population. 
8.3.4.1. 
Analysis of Primary Endpoint Change in PUL from Baseline to Week 52 
The primary endpoint, Change in the total score of Performance of Upper Limb [(PUL) 2.0 
version], from baseline to Week 52 will be analyzed using a random coefficient model with 
treatment, visit, visit-by-treatment interaction, , and baseline total score of Performance of Upper 
Limb value as fixed effects; the intercept and linear slope of visit as random effects. The primary 
analysis will be based on observed data from subjects in the ITT population. 
As sensitivity analysis, the analysis of covariance model (ANCOVA) model with Multiple 
Imputations (ANCOVA –MI) will be also applied. The model will include treatment and 
baseline total score of Performance of Upper Limb value. The primary analysis will be based on 
the ITT population. 
PUL 2.0 scale: 
• The PUL 2.0 scale, total score = 42. 
• High Level: Shoulder Dimension, 6 items: Max score = 12 
• Mid-level: Elbow Dimension, 9 items: Max score = 17 
• Distal level: Wrist and Finger Dimension, 7 items: Max score = 13 
8.3.4.2. 
Analyses of Secondary Endpoints 
Changes in ppFVC and ppPEF from Baseline to Week 52 
The Change from baseline to Week 52 in ppFVC will be analyzed using a random coefficient 
model with treatment, visit, visit-by-treatment interaction, and baseline ppFVC as fixed effects; 
the intercept and linear slope of visit as random effects. The analysis will be based on observed 
data from subjects in the ITT population. 
The Change from baseline to Week 52 in ppPEF will be analyzed using a random coefficient 
model with treatment, visit, visit-by-treatment interaction, and baseline ppPEF as fixed effects; 
the intercept and linear slope of visit as random effects. The analysis will be based on observed 
data from subjects in the ITT population. 
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Change in the Grip Strength of the Hands from baseline to Week 52, assessed by Hand 
Held Myometry (HHM) 
The Change from baseline to Week 52 in grip strength of the hands will be analyzed using a 
random coefficient model with treatment, visit, visit-by-treatment interaction, and baseline value 
as fixed effects; the intercept and linear slope of visit as random effects. The analysis will be 
based on observed data from subjects in the ITT population. 
Change in Left Ventricular Ejection Fraction percentage (LVEF %) from Baseline to 
Week 52, Assessed by MRI. 
Summary of Listing and the analyses of the change from baseline to week 52 in LVEF (%) 
assessed by MRI will be conducted in the ITT population. 
The change from baseline to Week 52 in left ventricular ejection fraction percentage (LVEF%), 
as assessed by MRI will be analyzed using a random coefficient model with treatment, visit, 
visit-by-treatment interaction, and baseline value as fixed effects; the intercept and linear slope 
of visit as random effects. 
As an exploratory endpoint, the dichotomous responder (proportion of patients with change from 
baseline in LVEF% ≥ 0 at Week 52) will be summarized and analyzed. The logistic regression 
model will be used to compare the proportion of subjects with change from baseline in LVEF% 
>=0). The model will include treatment and baseline LVEF%. 
For other secondary endpoints, MMRM 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. Other methods will be applied as 
appropriate. 
Detailed analyses of all secondary endpoints will be clearly outlined in the SAP. 
8.3.5. 
Exploratory analysis: 
Change in the subscores of three regional dimensions (High-level (shoulder), Mid-level 
(elbow), Distal-level (wrist and hand)) of PUL, from baseline to Week 52 
Summary of the listings and analyses of subscores of three regional dimensions (High-level 
(shoulder), Mid-level (elbow), Distal-level (wrist and hand)) of PUL will be summarized for 
subjects in the ITT population. 
The change from baseline to Week 52 in subscores of three regional dimensions (High-level 
(shoulder), Mid-level (elbow), Distal-level (wrist and hand)) of PUL will be analyzed using the 
Mixed Model for Repeated Measure (MMRM) with treatment, visit, treatment-visit interaction, 
and baseline endpoint value as fixed effects, with an unstructured variance - covariance matrix. 
Changes in Cardiac Fibrosis Score from Baseline to Week 52, Assessed by Late 
Gadolinium Enhancement (LGE). 
Summary of the listings and analyses of changes in cardiac fibrosis (LGE) will be based on the 
ITT population. 
The change from baseline to Week 52 in cardiac fibrosis score assessed by MRI and Mass of 
Late Gadolinium Enhancement (Scar Mass), will be analyzed using the Mixed Model for 
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Pa mre vl u ma b  
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Re peate d  Meas ure  ( M M R M) wit h  treat me nt, visit, treat me nt-visit  i nteracti o n, a n d baseli ne  
e n d p oi nt val ue as  fi xe d effects, wit h  a n u nstr u ct ure d varia n ce  - c o vari a nce matri x.  
I n a d ditio n, dic h ot o m o us res p o n der a nal ysis  ( pr o p orti o n of patie nts  wit h  c ha n ge fr o m b aseli ne  i n 
car diac fi br osis  sc or e 0 at Wee k  5 2) w ill be s u m marize d a n d a nal yze d. T he  l o gistic 
re gressi o n m o del will  be use d  t o c o m pare t h e pr o p orti o n of s u bjects wit h  c h a n ge fr o m b aseli ne 
i n car diac fi br osis > = 0.  T he m o del will  i ncl u de treat me nt a n d baseli ne car di ac  fi br osis sc ore. 
 
C h a n ge i n M y oc ar di al  Circ u mfere nti al  Str ai n  [ Gl o b al Circ u mfere nti al  
Str ai n  ( G C S) %] perce nt a ge  fr o m B aseli ne t o  Wee k  5 2, Assesse d  b y c ar di ac 
M RI.  
S u m mar y of t he listi n gs  a n d a nal yses of a n n ual c ha n ges fr o m b aseli ne f or t he Gl o bal M y ocar di al 
Circ u mfere ntial Strai n ( G C S) will be s u m marize d f or s u bjects i n t he  I T T p o p ulati o n, 
T he c ha n g e fr o m bas eli ne t o Wee k 5 2 i n G C S sc ore will be a nal y ze d usi n g  t he Mi xe d M o del f or 
Re peate d Meas ure  ( M M R M) wit h treat me nt, visit, treat me nt- visit i nteracti o n, a n d baseli ne 
e n d p oi nt val ue as fi xe d effects, wit h a n u nstr u ct ure d varia n ce  - c o varia nce matri x  
I n a d diti o n, dic h ot o m o us res p o n der a n al ysis ( pr o p orti o n of patie nts wit h c ha n ge fr o m b aseli ne 
i n G S C sc ore ≥ 0 at Wee k 5 2) will be s u m marize d  a n d a nal yze d. T he l o gistic re gressi o n m o del 
will be use d t o c o m pare t he pr o p orti o n of s u bjects wit h c ha n ge fr o m baseli n e i n G C S sc ore > = 0.  
T he m o del will i ncl u de treat me nt a n d bas eli ne car diac fi br osis sc ore.  
 
C h a n ges  i n Fi br osis Sc ore of  t he Bice ps Br ac hii  fr o m B aseli ne t o  Wee k  5 2, 
Assesse d  b y  M RI  
S u m mar y of t he listi n gs  a n d a nal yses of u p p er ar m ( bice p) m uscle  fi br osis assesse d b y M RI, will 
be s u m marize d b ase d o n  I T T p o p ulati o n; 
T he c ha n g e fr o m bas eli ne t o Wee k 5 2 i n fi br osis sc ore of t h e bice ps brac hii m uscle assesse d b y  
M RI   will be a nal yze d usi n g t he Mi xe d M o del f or Re peate d Meas ure  ( M M R M) wit h treat me nt, 
visi t, treat me nt- visit i nteracti o n, a n d baseli ne e n d p oi nt val ue as fi xe d effects, wit h a n 
u nstr uct ure d varia nce - c o varia nce matri x  
8. 3. 6.  
P h ar m ac o ki netic A n al yses  
A p o p ulati o n P K a nal ysis, as well as a n e x p os ure- res p o nse a n al ysis, will be defi ne d i n a se p arat e 
pla n.  
8. 3. 7.  
S afet y A n al yses 
All treat me nt -e mer ge nt a d verse e v e nts ( T E A Es)  will be s u m marize d b y treat me nt ar m,  
i ncl u di n g: T E A Es Gra de ≥3, treat me nt-e mer ge nt s eri o us a d vers e e v e nts ( T E S A Es), deat hs, a n d 
T E A Es lea di n g t o st u d y or i n vesti gati o nal pr o d uct disc o nti n uati o n. 
Cli nicall y si g nifica nt c ha n ges fr o m baseli ne i n vit al si g ns a n d la b orat or y tests will be  
s u m marize d.  H y perse nsiti vit y/a na p h ylactic reacti o ns will be m o nit ore d. 
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Additionally, the following safety analyses will be conducted: 
• Number and percentage of subjects with bone fractures 
• Ulna length measurements for indirect measure of annualized growth velocity 
(cm/year) for subjects under the age of 18 
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 the Sponsor 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 the Sponsor 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 the Sponsor. 
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 the Sponsor 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 
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informed consent discussion, with any additional signatures obtained as required by applicable 
local regulations and IRB/IEC requirements. Each subject will be informed that participation is 
voluntary and that he/she can withdraw from the study at any time.  All subjects will receive a 
copy of the signed and dated ICF. 
If there are any changes to the IRB/IEC approved ICF during the subjects’ participation in the 
study, the revised ICF must receive the IRB/IEC’s written approval before use and subjects must 
be re-consented to the revised version of the ICF, if/as required by the IRB/IEC. 
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. 
The Sponsor 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.  The Sponsor 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 
the Sponsor 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 onto CRFs by authorized site personnel or will be 
provided as a data transfer from authorized service providers (such as laboratory results from a 
central laboratory, central PFT reviewer, 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 
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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 reports will be made 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, FibroGen, 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 or the 
Sponsor or 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. 
Any Investigator(s) added as investigational staff to the form FDA 1572 or equivalents 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 
Bergsma A, Lobo-Prat J, Vroom E, Furlong P, Herder JL, Workshop Participants. 1st Workshop 
on Upper-Extremity Assistive Technology for People with Duchenne: State of the art, emerging 
avenues, and challenges: April 27th 2015, London, United Kingdom. Neuromuscular disorders: 
NMD. 2016;26(6):386–393. pmid:27133663 
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 
Confidential
Page 70 of 84


Pamrevlumab 
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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. 
Gandolla M, Antonietti A, Longatelli V, Biffi E, Diella E, et al. (2020) Test-retest reliability of 
the Performance of Upper Limb (PUL) module for muscular dystrophy patients. PLOS ONE 
15(9): e0239064.  
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 
Mayhew A, Mazzone ES, Eagle M, Duong T, Ash M, Decostre V, et al. Development of the 
Performance of the Upper Limb module for Duchenne muscular dystrophy. Developmental 
Medicine and Child Neurology. 2013;55(11):1038–1045. pmid:23902233 
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 
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Pamrevlumab 
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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. 
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 
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 
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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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APPENDICES 
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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
 
 
 
 
 
 
Screening 
Period 
(4 Weeks) 
Treatment Period (Weeks) a, b 
Safety 
Follow Up 
Periodp 
 
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 56/ 
EOS/p
ETe 
60 Days 
ost dos 
(phone 
call) 
Informed 
Consent/Assent 
x 
Eligibility 
Assessment 
x 
xr 
Randomization 
xr 
Demographics 
x 
Medical History 
x 
Vital Signs l 
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 
x 
Pulmonary 
Function Tests / 
Height (ulna 
length) d 
x 
xm 
x 
x 
x 
x 
x 
xq 
Muscle Function 
Tests j 
x 
xm 
x 
x 
x 
x 
xq 
Physical 
Examination f 
x 
x 
x 
x 
x 
x 
x 
Weight/Weight 
Based Dose 
Adjustment e 
x 
x 
x 
x 
x 
Cardiac and 
Muscle MRI k 
x 
x 
xq 
PK/HAHAi 
x 
x 
x 
x 
x 
 
x 
 
 
 
x 
 
x 
 
x 
Genetic 
Analysis n 
x 
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Duchenne Video 
Assessment 
xo 
xo 
xo 
xo xo,q 
Pamrevlumab 
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 / 
SAEs g 
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 
Concomitant 
Medications h 
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.) Unscheduled visit assessments (procedures) will be determined by the investigator. Study teams will include information in the protocol (Section 6, 
Assessment of Efficacy) and in the Study Reference Manual for expectations at an Unscheduled Visit. 
c.) At the Early Termination visit, PFTs and MFTs must be conducted. MRIs do not have to be repeated if the last one was performed within 4 weeks of this 
visit. 
d.) PFTs: forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow rate. Height will be measured at each lung function measuring 
interval using ulna length to approximate standing height. 
e.) Weight will be measured at Screening and every 12 weeks thereafter to determine dose for the subsequent 12-week interval. Weight can be collected up to 
14 days before the dose adjustment visit. 
f.) Full physical exam including chest auscultation 
g.) 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 specific guidelines in the electronic case report form 
completion guidelines. 
See Section 7 for follow-up of AEs. 
h.) Concomitant medications and nondrug therapies must be reported beginning after informed consent is obtained and ending 60 days after the last treatment. 
Refer to Section 5.2.2 for additional information on prohibited concomitant medications 
i.) HAHA, HAHA-NA and PK samples.  See Appendix 2 for PK, HAHA, and HAHA-NA sampling time points.  
j.) MFTs: Performance of Upper Limb (v. 2.0), and Hand Grip Test. 
k.) Local labs may be drawn prior to MRIs at the discretion of the investigator. 
l.) 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. 
m.) 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. 
n.) Genetic Analysis samples will be collected in PAXgene tube; samples will be collected only from subjects who consent for this test.  If subject consents to 
this optional sample, it may also be collected at an Unscheduled timepoint if it is not collected initially at Day 0. 
o.) Duchenne Video Assessment to be performed remotely within the interval between the prior scheduled study visit and next scheduled study visit. 
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p.) 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 (+3 days) after the last infusion visit. 
q.) PFTs, MFTs, DVA and MRI only to be done at the early termination visit 
r.) Randomization may be performed within 2 days prior to Day 0 visit, after subject is confirmed eligible (see footnote “m”). 
 
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APPENDIX 2. PHARMACOKINETIC AND PHARMACODYNAMIC 
SAMPLING 
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.  
 
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 at this timepoint. 
 
e) For reconsented subjects, PK, HAHA, HAHA-NA, and tryptase sampling will be required at the time of 
immunogenic reaction.  Samples should be drawn within 24 hours of the anaphylactic episode. 
 
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. 
 
g) Tryptase should be drawn within 1 to 6 hours of immunogenic reaction (anaphylactic episode) or at least 24 
hours within of the anaphylactic episode.  
 
h) Genetic samples will be collected only from subjects who consent for this test.  If subject consents to this 
optional sample, it may also be collected at an Unscheduled timepoint if it is not collected initially at Day 
0. 
 
Timepoint a 
PK 
(Plasma) 
(Optional Consent) 
HAHAb 
(Plasma) 
HAHA-NAb 
(Plasma) 
Genetic 
Analysish 
(Whole blood) 
(Optional Consent) 
Tryptase 
Day 0 
Xc 
Xf 
Xf 
X 
 
Week 2 
Xc 
Week 8 
Xc 
Week 16 
Xc 
Week 24 
Xc 
X
f 
X
f 
Week 32 
Xc 
X
f 
X
f 
Week 40 
Xc 
X
f 
X
f 
Week 48 
Xc 
X
f 
X
f 
Week 56/EOS 
or ET 
Xd 
Xf 
Xf 
Immunogenic 
Reaction 
Xe 
Xe 
Xe 
 
Xg 
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APPENDIX 3. 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 in the OLE will then 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 
Endpoints 
Function assessment: 
• Annual mean change in the total score of Performance of Upper Limb [(PUL) 2.0 
version]. 
•  Change in the subscores of three regional dimensions (High-level (shoulder), Mid-
level (elbow), Distal-level (wrist and hand)) of PUL, from baseline to Week 52 
Pulmonary assessment: 
• Annual mean change in percent predicted forced vital capacity (ppFVC), assessed by 
spirometry. 
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• Annual mean change in percent predicted peak expiratory flow (ppPEF), assessed by 
spirometry. 
• Performance assessment:Annual mean change in the Grip strength of the hands 
extremities, assessed by Hand Held Myometry (HHM). 
Cardiac assessment (Exploratory Assessment): 
• Annual mean change in Left Ventricular Ejection Fraction percentage (LVEF %), 
assessed by MRI. 
• Annual mean change in Cardiac fibrosis score, assessed by Late Gadolinium 
Enhancement (LGE). 
• Annual mean change in Myocardial Circumferential Strain [Global Circumferential 
Strain (GCS)] percentage, assessed by cardiac MRI. 
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. 
• Ulna length measurements for indirect measure of annualized growth velocity for 
subjects under the age of 18 
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 
current 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. 
 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 Sponsor Medical 
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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.  Vital signs to be collected one time during the safety follow-
up. 
• 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 and weight will be performed every 12 weeks. The 
Performance of the Upper Limb (PUL v. 2.0), will be performed to assess changes in 
upper extremity strength and the Performance of the Grip score will be performed to 
assess changes in hands strength.  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. 
• 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. 
• Pulmonary function tests (PFTs) will be performed using the same central vendor 
from the main study and completed every 24 weeks to assess changes in lung 
function: forced vital capacity (FVC), and peak expiratory flow rate (PEF; PEFR), 
and forced expiratory volume in 1 second (FEV1). 
• Chemistry and hematology tests (Chemistry panel, CBC with differentials, and liver 
function tests (LFTs)) should be completed centrally at every 24 week interval.  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 and tryptase drawn within 24 hours of 
immunogenic reaction (anaphylactic episode). A window of “within 24 hours of 
reaction” could be at any point following the infusion such as 30 minutes post-
infusion but not to exceed 24 hours following reaction.   This includes timepoints in 
which PK, HAHA, and HAHA-NA were drawn prior to the reaction as well.  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.  The tryptase sample should be drawn within 1 to 6 hours of immunogenic 
reaction (anaphylactic episode) but all samples should at least be collected within 24 
hours after the anaphylactic episode.  See Appendix 2 for more detail of 
immunogenic reaction blood draws.   
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• Any assessments repeated as a part of the main study and all AEs prior to first dose in 
OLE are considered as part of the main study. 
• Cardiac MRIs to evaluate left ventricle ejection fraction, cardiac fibrosis, and 
myocardial circumferential strain to be performed as an exploratory assessment 
every 52 weeks during the OLE. 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 conducted prior to MRI will not be captured 
in the clinical database. 
Subjects who complete the dosing period or early terminate will have a final follow-up visit 4 
weeks (±3 days) and a final safety follow-up phone call 60 days (+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. 
Statistical Considerations 
Data collected during the extension period will be summarized descriptively along with the main 
study. 
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APPENDIX 4. OLE SCHEDULE OF ASSESSMENTS 
 
 
 
 
Q2 
WEEKS 
(± 3 days) 
 
 
Q12 weeks 
(± 3 days) 
 
 
Q 24 weeks 
(± 3 days) 
 
 
Q52 Weeks (± 3 
days)/EOT 
 
Final Safety Follow- 
up Visit 
4 Weeks (± 3 days) 
after Last treatment 
EOS/ET 
Final 
Safety 
phone call 
60 Days 
(+3 
days) 
after 
last 
treatment 
Informed Consent & Assent/Eligibilitya 
 
 
 
 
 
 
Vital Signsb 
x 
x 
x 
x 
x 
 
Chemistry & Hematology (Central lab) 
 
 
x 
 
x 
 
PFTs / Height (ulna length)e 
 
 
x 
xh 
xc 
 
Muscle Function Testsd 
 
x 
x 
xh 
xc 
 
Physical Examinationg 
 
 
x 
 
x 
 
Cardiac MRI 
 
 
 
x 
 
 
Weight/Weight Based Dose Adjustmentf 
 
x 
x 
 
 
 
Specialty Labs (PK, HAHA, and HAHA-NA)i ) 
 
 
x 
 
x 
 
Pamrevlumab Infusion 
x 
x 
x 
x 
 
 
AEs / SAEs 
x 
x 
x 
x 
x 
x 
Concomitant Medications 
x 
x 
x 
x 
x 
x 
 
Abbreviations: AE = adverse event; EOS = End of Study; EOT = End of Treatment; ET= Early Termination; PFTs = Pulmonary Function Test 
 
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 infusion visit: within 30 minutes pre-infusion, and within 30 minutes after 
completion of infusion.  For EOS/ET, vitals to be completed one time only. 
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c) MFTs and PFTs do not need to be done at the final Safety follow-up visit, ONLY during an ET visit and ONLY if the last test was not conducted within 8 weeks 
of the visit. 
d.) Muscle Function Tests (MFTs): Performance of Upper Limb (v. 2.0), and Grip Test. 
e.) Pulmonary Function Tests (PFTs) include forced vital capacity, forced expiratory volume in 1 second, and peak expiratory flow rate to be performed.  Height 
should be measured at each PFT interval using ulna length to approximate standing height. 
f.) Weight will be measured every 12 weeks to determine dose for the subsequent 12-week interval. Weight is collected during the dose adjustment visit or can be 
done up to two weeks in advance. 
g.) Full physical exam including chest auscultation is completed per the institution’s local practice (i.e., every 24 weeks) 
h.) MFTs and PFTs only to be done at the end of treatment visit (last infusion visit), otherwise, they are done every 12 or 24 weeks, respectively 
i.)  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 detail of blood 
draws including sample required for immunogenic reaction.   
 
 
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Signature Page for VV-CLIN-013263 v1.0
Signature Page for VV-CLIN-013263 v1.0
Approval Task
09-Nov-2022 22:01:49 GMT+0000

SAP_001.pdf: 
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 Subjects with Non-ambulatory Duchenne 
Muscular Dystrophy (DMD) 
PROTOCOL NUMBER: 
Protocol FGCL-3019-093 
Amendment 6:  01 November 2022 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
STUDY DRUG: 
Pamrevlumab 
INDICATION: 
Duchenne Muscular Dystrophy (DMD) 
SAP VERSION 
Final 1.0 
RELEASE DATE 
May 23, 2023 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and proprietary to FibroGen, Inc. No part of 
this document or any of the information contained herein may be transmitted, disclosed, shared, 
reproduced, published or utilized by any persons without prior written authorization by FibroGen, Inc.
NCT: NCT04371666


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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. 
Signature: see appended final page for 21CFR Part 11 compliant approval 
Initiator: 
, FibroGen, Inc. 
Reviewed by: 
 
 FibroGen, Inc. 
 
 FibroGen, Inc. 
 FibroGen, Inc. 
 
 FibroGen, Inc. 
 
 FibroGen, Inc. 
 FibroGen, Inc.  
 
 FibroGen, Inc. 
 
FibroGen, Inc. 
Signature Significance 
The following significance is lent to the signatures on the Approvals page of this document. 
Signatory 
Significance 
Initiator 
By signing, the author is attesting that the content of the document is 
complete and accurate. 
Reviewer 
By signing, the reviewer(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 
1.0 
23May2023 
Final approved version 
 
 
 


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LIST OF TABLES 
Table 1: 
Testing Sequence of Primary and Secondary Endpoints ............................................ 23 
Table 2: 
Laboratory Tests ......................................................................................................... 40 
Table 3: 
Criteria for Potentially Clinically Significant Vital Signs .......................................... 42 
Table 4: 
Analysis Date Derivation Rules for Missing/Incomplete AE Onset Date ................. 50 
Table 5: 
Analysis Date Derivation Rules for Missing/Incomplete AE Stop Date ................... 51 
Table 6: 
Analysis Visit Window for Vital Signs ...................................................................... 53 
Table 7: 
Analysis Visit Window for Physical Examination ..................................................... 54 
Table 8: 
Analysis Visit Window for Pulmonary Function Tests (PFT) ................................... 54 
Table 9: 
Analysis Visit Window for Muscle Function Tests (MFT) ....................................... 54 
Table 10: Analysis Visit Window for Laboratory Tests ............................................................. 55 
Table 11: Specifications for Page Layout ................................................................................... 64 
Table 12: Significant Digits of Summary Statistics ................................................................... 66 
 


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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................................... 1 
SIGNATURES AND APPROVALS .............................................................................................. 2 
CHANGE HISTORY ...................................................................................................................... 3 
LIST OF TABLES........................................................................................................................... 4 
TABLE OF CONTENTS ................................................................................................................ 5 
LIST OF FIGURES ......................................................................................................................... 7 
LIST OF ABBREVIATIONS ......................................................................................................... 8 
1. 
INTRODUCTION ...................................................................................................... 11 
2. 
STUDY OBJECTIVES .............................................................................................. 11 
3. 
STUDY DESIGN ....................................................................................................... 11 
3.1. 
Overview .................................................................................................................... 11 
3.2. 
Study Population ........................................................................................................ 11 
3.3. 
Sample Size Determination ........................................................................................ 11 
3.4. 
Randomization and Treatment Assignment ............................................................... 12 
3.5. 
Study Periods .............................................................................................................. 12 
3.6. 
Study Assessments ..................................................................................................... 13 
4. 
STUDY ENDPOINTS ............................................................................................... 14 
4.1. 
Primary Endpoint ....................................................................................................... 14 
4.1.1. 
Function assessment: .................................................................................................. 14 
4.2. 
Secondary Endpoints .................................................................................................. 14 
4.3. 
Safety Assessments .................................................................................................... 14 
4.4. 
Exploratory Endpoints ................................................................................................ 14 
4.5. 
Pharmacokinetics/pharmacodynamics (PK/PD) assessment ...................................... 15 
5. 
GENERAL STATISTICAL CONSIDERATIONS ................................................... 15 
5.1. 
General Conventions .................................................................................................. 15 
5.1.1. 
Analysis for Categorical Endpoints ............................................................................ 15 
5.1.2. 
Analysis for Continuous Endpoints ............................................................................ 15 
5.2. 
Analysis Sets .............................................................................................................. 16 
5.2.1. 
Intent-to-Treat Set (ITT) ............................................................................................ 16 
5.2.2. 
Modified ITT Population (mITT) ............................................................................... 16 
5.2.3. 
Per-Protocol Set (PPS) ............................................................................................... 16 
5.2.4. 
Safety Analysis Set (SAF) .......................................................................................... 16 


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5.3. 
General Data Handling Rules and Presentation Specifications .................................. 16 
5.3.1. 
Analysis Period ........................................................................................................... 16 
5.3.2. 
Baseline and Change from Baseline Definitions ........................................................ 17 
5.3.3. 
Study Day Calculation ................................................................................................ 17 
5.3.4. 
General Instructions on TFLs ..................................................................................... 17 
5.3.5. 
Handling Dropouts and Missing Data ........................................................................ 17 
5.4. 
Interim Analysis and Data Monitoring Committee .................................................... 18 
5.5. 
Analysis Visit Windows ............................................................................................. 18 
6. 
STATISTICAL ANALYSES ..................................................................................... 18 
6.1. 
Subject Enrollment and Disposition ........................................................................... 18 
6.1.1. 
Eligibility .................................................................................................................... 18 
6.1.2. 
Subject Accountability and Disposition ..................................................................... 19 
6.2. 
Important Protocol Deviations ................................................................................... 19 
6.3. 
Demographics and Baseline Characteristics .............................................................. 19 
6.3.1. 
Demographics and Baseline Characteristics .............................................................. 19 
6.3.2. 
Baseline DMD Disease Characteristics ...................................................................... 20 
6.3.3. 
Medical History .......................................................................................................... 21 
6.4. 
Prior and Concomitant Medications ........................................................................... 22 
6.5. 
Study Drug Exposure and Treatment Compliance ..................................................... 22 
6.5.1. 
Study Drug Exposure ................................................................................................. 22 
6.5.2. 
Treatment Compliance ............................................................................................... 22 
6.6. 
Efficacy Analyses ....................................................................................................... 23 
6.6.1. 
Primary Endpoint Estimands and Analyses ............................................................... 23 
6.6.2. 
Secondary Endpoint Estimands and Analyses ........................................................... 33 
6.6.3. 
Exploratory Analyses ................................................................................................. 36 
6.6.4. 
Subgroup Analyses of Specified Endpoints ............................................................... 39 
6.7. 
PK Analyses ............................................................................................................... 39 
6.8. 
Safety Analyses .......................................................................................................... 39 
6.8.1. 
Adverse Events ........................................................................................................... 39 
6.8.2. 
Clinical Laboratory Assessments ............................................................................... 40 
6.8.3. 
Vital Signs .................................................................................................................. 41 
6.8.4. 
Physical Examination ................................................................................................. 42 
6.8.5. 
Electrocardiogram ...................................................................................................... 42 


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6.8.6. 
Special Safety Events ................................................................................................. 42 
6.8.7. 
Growth Velocity (cm/year) ......................................................................................... 42 
6.8.8. 
Bone Fractures ............................................................................................................ 43 
6.8.9. 
Subgroup Analyses of Safety Endpoints .................................................................... 43 
6.9. 
Biomarker Endpoint Analysis .................................................................................... 43 
6.10. 
Immunogenicity Analysis ........................................................................................... 43 
7. 
CHANGES FROM PROTOCOL ............................................................................... 44 
8. 
REFERENCES ........................................................................................................... 46 
9. 
APPENDICES ............................................................................................................ 49 
APPENDIX 1. HANDLING MISSING/INCOMPLETE DATES ............................................. 50 
APPENDIX 2. ANALYSIS VISIT WINDOWS ........................................................................ 53 
APPENDIX 3. PERFORMANCE OF THE UPPER LIMB (PUL) MODULE.......................... 56 
APPENDIX 4. LABORATORY TEST CTCAE CRITERIA .................................................... 62 
APPENDIX 5. GENERAL SPECIFICATIONS FOR TABLES, LISTINGS, FIGURES ......... 64 
1. 
Software Used ............................................................................................................ 64 
2. 
General ....................................................................................................................... 64 
3. 
Page Layout ................................................................................................................ 64 
4. 
Titles and Footnotes ................................................................................................... 65 
5. 
Table, Figure, Listing Metadata ................................................................................. 65 
6. 
Significant Digits of Summary Statistics ................................................................... 66 
7. 
Figure Specifications .................................................................................................. 66 
APPENDIX 6. CHINA CDE REQUIREMENTS ...................................................................... 68 
 
LIST OF FIGURES 
Figure 1: 
FGCL-3019-093 Study Schema ................................................................................. 12 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
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 
BP 
Blood Pressure 
BPM 
Beats Per Minute 
BSA 
Body Surface Area 
BTR 
Best-Test Read 
CBC 
Complete Blood Count 
CDE 
Center for Drug Evaluation (China) 
CRF 
Case Report Form 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBL 
Database Lock 
DCM 
Dilated Cardiomyopathy 
DMD 
Duchenne Muscular Dystrophy 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
EE 
Efficacy Evaluable 
EoS 
End of Study 
EoT 
End of Treatment 
FEV1 
Forced Expiratory Volume in 1 Second 
FG-3019 
FibroGen-3019 (Recombinant Human Monoclonal Antibody), Pamrevlumab 
FVC 
Forced Vital Capacity 
GCS 
Global Circumferential Strain 
HAHA 
Human Anti-Human Antibody 


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Abbreviation 
Definition 
HHM 
Handheld Myometry 
ICF 
Informed Consent Form 
IP 
Investigational Product 
ITT 
Intent-to-Treat 
IV 
Intravenous 
kg 
Kilogram 
LGE 
l
Late Gadolinium Enhancement 
LLN 
Lower Limit of Normal 
LTFU 
Lost to Follow-up 
LVEF 
Ventricular Ejection Fraction 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
MMRM 
Mixed Model Repeated Measures 
MRI 
Magnetic Resonance Imaging 
NCI 
National Cancer Institute 
NCS 
Not Clinically Significant 
OLE 
Open Label Extension 
PD 
Pharmacodynamics 
PEF 
Peak Expiratory Flow 
PFT 
Pulmonary Function Test 
PK 
Pharmacokinetic 
ppFVC 
percent predicted FVC 
PRO 
Patient Reported Outcome 
PT 
Preferred Term 
PTT 
Partial Prothrombin Time 
PUL 
Performance of Upper Limb 
QoL 
Quality of Life 
ROM 
Range of Motion 
RCM 
Random Coefficient Model 
SAF 
Safety Analysis Set 
SAE 
Serious Adverse Event 


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Abbreviation 
Definition 
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 
ULN 
Upper Limit of Normal 
WHODD 
World Health Organization Drug Dictionary 


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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-3019-093 Amendment 6, 
01 November 2022. Specifications of tables, figures, and listings (TFL) are contained in a separate 
document.  The statistical analyses and summary tabulations described in this SAP will 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 an 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 PK analysis, as well as an exposure-response analysis, will be defined in a 
separate PK analysis plan.  
Based on regional regulatory filing needs, regional specific population 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 in subjects with non-ambulatory Duchenne 
Muscular Dystrophy (DMD) (age 12 years and older). 
3. 
STUDY DESIGN 
3.1. 
Overview 
Study FGCL-3019-093 is a Phase 3, global, randomized, double-blind, placebo-controlled multi-
center study. The goals of the study are to evaluate the efficacy and safety of pamrevlumab 
compared to placebo in subjects with non-ambulatory Duchenne Muscular Dystrophy over a 
52-week period.  
3.2. 
Study Population 
Approximately 92 male subjects will be enrolled in this trial, globally.  
3.3. 
Sample Size Determination 
This section is updated based on latest publications and the study enrollment.   
This study is planned to enroll a total of approximately 92 subjects with a 1:1 randomization ratio 
of assigning to pamrevlumab or placebo, respectively. With Performance of Upper Limb (PUL) 
version 2.0, the sample size of 92 subjects is needed to detect a treatment difference of 2.0 between 
treatment arms in change from baseline in the total score of PUL at Week 52, assuming a standard 
deviation of 2.9 with a 90% power, based on a two-sided two-sample t-test at the alpha level of 
0.05.  A sample size of 82 subjects will provide the study with at least 85% power to detect the 
same assumed treatment difference.  


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3.4. 
Randomization and Treatment Assignment 
Subjects will be randomized with a 1:1 ratio to one of the two study treatment arms as follows:  
• Arm A: pamrevlumab 35 mg/kg IV infusion Q2 weeks + systemic deflazacort or equivalent 
potency of corticosteroids administered orally. 
• Arm B: matching placebo IV infusion Q2 weeks + systemic deflazacort or equivalent 
potency of corticosteroids administered orally. 
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 period (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. If a subject discontinues the 
main study period 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 should 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.  
 
Figure 1: 
FGCL-3019-093 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 non-ambulatory Duchenne muscular 
dystrophy (age 12 years and older).  
The following assessments will be assessed by the schedules defined in the protocol (Schedule of 
Assessments (SoA) in the Appendix of the protocol): 
• Performance of Upper Limb (PUL) V2.0  
• Pulmonary Function Test (PFT) including 
o Forced Vital Capacity (FVC) 
o Peak Expiratory Flow (PEF)  
o Forced Expiratory Volume in 1 second (FEV1) 
• Grip strength of the hands by Handheld Myometry (HHM) 
• Left Ventricular Ejection Fraction percentage (LVEF %), assessed by magnetic resonance 
imaging (MRI) 
• Duchenne Video Assessment (DVA) 
• Dilated Cardiomyopathy (DCM) by genetic analysis 
• Fibrosis score of the biceps brachii, assessed by MRI 
• Cardiac fibrosis score, assessed by Late Gadolinium Enhancement (LGE) 
• Myocardial Circumferential Strain [Global Circumferential Strain (GCS)], assessed by 
cardiac 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, physical exams, etc. 
The following assessments will be assessed centrally by independent external vendors or study 
committees: PFTs, MRI, PUL V2.0. and DVA. 
In addition, an independent Data Monitoring Committee (DMC) will review safety and other 
clinical data (with the authority to unblind such data as needed) on a periodic basis to monitor 
overall subject safety. 
 


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4. 
STUDY ENDPOINTS  
4.1. 
Primary Endpoint 
4.1.1. 
Function assessment:  
• Change in the total score of Performance of Upper Limb [(PUL) version 2.0], from 
baseline to Week 52 
4.2. 
Secondary Endpoints 
• Change in percent predicted forced vital capacity (ppFVC) from baseline to Week 52, 
assessed by spirometry 
• Change in the total score of Mid-level of PUL from baseline to Week 52 
• Change in the Grip strength of the hands from baseline to Week 52, assessed by 
Handheld Myometry (HHM) 
• Change in Left Ventricular Ejection Fraction percentage (LVEF %) from baseline to 
Week 52, assessed by MRI 
• Composite of endpoints 
Mean observed z score for each of the 3 composite endpoints (PUL, ppFVC), (PUL, 
ppFVC, Grip Strength), (PUL, ppFVC, Grip Strength, LVEF%). 
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, hypersensitivity/anaphylactic reactions, and 
infusion 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 
• Ulna length measurements for indirect measure of growth velocity (cm/year) for 
subjects under the age of 18 
4.4. 
Exploratory Endpoints 
• Change in the subscores of the regional dimensions (High-level (Shoulder), Distal-level 
(Wrist and Hand)) of PUL, from baseline to Week 52 
• Change in Duchenne Video Assessment (DVA) severity percentage from baseline to 
Week 52 
• Change in percent predicted Forced Expiratory Volume at 1 second (ppFEV1) from 
baseline to Week 52 


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• Change in percent predicted peak expiratory flow (ppPEF) from baseline to Week 52, 
assessed by spirometry 
• Progression of Dilated Cardiomyopathy (DCM) by genetic analysis at Week 52 
Fibrosis/MRI assessments:  
• Changes in fibrosis score of the biceps brachii, from baseline to Week 52, assessed by 
MRI 
• Changes in cardiac fibrosis score from baseline to Week 52, assessed by Late 
Gadolinium Enhancement (LGE) 
• Change in Myocardial Circumferential Strain [Global Circumferential Strain (GCS)] 
percentage from baseline to Week 52, assessed by cardiac 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. 
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 of proportions for each treatment group will be 
calculated using the Clopper-Pearson method as appropriate. 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 selected 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 mITT/ITT or Safety Analysis Set, except for the parameters 
specifically indicated otherwise.  
Efficacy and safety analyses for treatment comparisons will be based on data observed during the 
main study period (52 weeks).  


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The statistical comparisons will be done 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. 
Modified ITT Population (mITT) 
The mITT population enriched for expected change will include subjects from the ITT set with a 
PUL Entry score >= 2 (excluding PUL entry scores of 1) at baseline. 
5.2.3. 
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 PUL assessments, did not early terminated 
from treatment or study, and no major protocol deviation(s) that significantly impact efficacy 
analyses. 
5.2.4. 
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. 
 
5.3. 
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 the 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 didn’t enroll in the 
OLE period. 
For the safety analysis, all safety assessments beyond 60 days of last dose will be excluded from 
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5.3.1.2. 
On-Treatment Period 
The on-treatment analysis includes only the assessments that are observed during On-Study Period 
as defined above (Section 5.3.1.1), 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 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. 
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 


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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 FDA/EMA Guidance: During the COVID-19 pandemic, the visit modality 
(e.g.: in-person versus remotely) and scheduling may be adjusted and conducted at the discretion of 
the Investigator, in accordance with the site’s rules and recommendations, and using all necessary 
precautions. If a visit 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. 
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 
measurement closest to the target date or the later assessment if there is a tie 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 is to 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 


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• 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), mITT, Per-Protocol Set (PPS), 
completed the main study, entered the OLE period, and discontinued prematurely from treatment 
and study in the main study 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 
Important protocol deviations of interest may include, but are not limited to, the following: 
• 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 mITT, 
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, age group (≤16 


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years, >16 years), ethnicity, race, weight, body-mass index (BMI), side of dominant hand, and 
body surface area (BSA), PUL 2.0 total score and subscores. 
Computation formula: 
BSA = [Weight 0.425 (kg) * Height 0.725 (cm)] x 0.007184 
Age = Year of informed consent date – Year of birth 
Height (cm) = 4.605 * Ulna length (cm) +1.308 * Age at PFT assessment+28.003, where 
age < 18 years old during PFT visits; For subjects that enter the study at age 18 or turn 18 
during the study, the last recorded ulna length/height will be used for the remainder of the 
study. 
 
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, but not limited to,: 
1. Age in years when DMD was diagnosed = Year of date of diagnosis - Year of birth 
2. Age when subject became non-ambulant = Year of date of when subject became non-
ambulant - Year of birth 
3. Years since subject became non-ambulant = Current age – Age when subject became non-
ambulant 
4. Age when subject began ventilation support = Year of date of subject began ventilation 
support- Year of birth 
5. Ventilation support: yes or no. If yes, years since subject began ventilation support = 
Current age– Age when subject began ventilation support. 
6. 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. 
7. 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 = 
Year of Day 1 Visit Date - Year of spine surgery,   
8. Genetic characteristics (check all that apply) 
− Exonic deletion 
− Duplication 
− Point mutation 
− None of above 
− Unknown 
Additionally, the following baseline disease characteristics, but are not limited to, will be 
summarized. 


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9. Bone parameters 
• Bone fractures (Section 6.8.8 ) 
• Scoliosis  
• Osteoporosis 
• Spine surgery  
10. Cardiac parameters 
• Cardiomyopathy  
• LVEF (%)  
11. Respiratory parameters 
• Ventilation support  
• Years since ventilation support 
• Sleep apnea  
• ppFVC  
12. Metabolic parameters 
• Insulin resistance 
• Obesity  
• Vit D deficiency 
• Delayed puberty 
13. Corticosteroids (CS) use  
• Age at CS initiation 
• Prednisone/Prednisolone  
• Deflazacort  
• Regimen 
− Daily 
− Other 
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 26.0 or higher), will be summarized for the ITT 
Analysis Set.  Subject medical history listings will be provided.  


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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. 
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). 
Duration of weekly exposure will be tabulated by treatment group for the Safety population.  
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 


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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 the 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 mITT during the On-Study period 
(Section 5.3.1.1), unless noted otherwise. Sensitivity analysis on ITT will also be performed on 
primary and secondary endpoints as supportive evidence. 
Table 1: 
Testing Sequence of Primary and Secondary Endpoints 
Testing Sequence 
Endpoint 
1 (primary endpoint) 
Change in the total score of Performance of Upper Limb [(PUL) version 2.0], 
from baseline to Week 52. 
2 
Change in percent predicted Forced Vital Capacity (ppFVC) from baseline to 
Week 52, assessed by spirometry. 
3 
Change in the total score of Mid-level of PUL from baseline to Week 52 
4 
Change in the grip strength of the hands from baseline to Week 52, assessed 
by Hand-Held Myometry (HHM). 
5 
Change in Left Ventricular Ejection Fraction percentage (LVEF %) from 
baseline to Week 52, assessed by MRI. 
 
6.6.1. 
Primary Endpoint Estimands and Analyses  
The primary efficacy endpoint in this study is defined as Change from Baseline in the total score of 
Performance of Upper Limb [(PUL) version 2.0] at Week 52. 
PUL 2.0 scale:  
• The PUL 2.0 scale, with maximum total score = 42 


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• High Level: Shoulder Dimension, 6 items: Max score = 12 
• Mid-level: Elbow Dimension, 9 items: Max score = 17 
• Distal level: Wrist and Hand Dimension, 7 items: Max score = 13 
Only 1 item in each domain is allowed missing. The score of the missing item will be imputed by 
the mean of the non-missing items in the domain. If the total score of any domain is missing (the 
high-level domain only applies to subjects with Item A score ≥ 3), then the total score will be 
missing. The total score of PUL is the sum of the total scores of the three domains (if Item A score 
≥ 3) or two domains (Mid-level and Distal level, if Item A score <3). 
The last measurement prior to first dose of study drug from Muscle Function Tests (MFTs) at Day 
1 will be used to establish baseline. 
The primary efficacy endpoint will be analyzed using mITT 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 PUL at Week 52 for the pamrevlumab arm = 
Change from Baseline in the total score of PUL at Week 52 for the placebo group 
Versus: 
H1: Change from Baseline in the total score of PUL at Week 52 for the pamrevlumab arm 
≠ Change from Baseline in the total score of PUL 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 with the Random Coefficient Model (RCM) 
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. 
6.6.1.1.2. Population of Interest 
The mITT population will used as defined in Section 5.2.2 . 
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 mITT 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. 


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6.6.1.1.4. Analysis Variable 
Change from baseline in the total score of all PUL assessments in the randomization treatment 
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 random coefficient linear regression model (RCM), where within-patient errors follow a 
random coefficient regression model will be performed. The RCM model will include fixed effects 
of time, treatment, treatment-by-time interaction, with baseline ordinal PUL entry score as 
covariate. The time in the RCM model will be calculated as the elapsed weeks (considered as a 
continuous variable with 1 decimal place) from first dose date (or randomization date for subjects 
who drop out prior to any study medication) to the assessment date. All valid values including 
from unscheduled visits will be included.  
The residual plot from the PROC MIXED output will be examined. If the residual plot shows a 
systematic pattern rather than a random scatter, then the linearity assumption may not be 
appropriate. In case of non-linearity, MMRM will be used as the primary analysis method, which is 
currently listed as one of the sensitivity analyses in next section. 
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. When the random effects model 
does not converge or does not have a positive definite Hessian, the fixed effects instead of random 
effects will be performed instead. The Least Square Mean (LSMean) (SE) and 95% CI estimated 
changes from baseline to Week 52 will be presented. 
Sample SAS code: 
PROC MIXED DATA = XXX;  
  CLASS TRTPN SUBJID ItemAgrp;   
  MODEL CHG = TRTPN AWK TRTPN*AWK ItemAgrp / RESIDUAL CL COVB DDFM=KR; 
  RANDOM AWK / SUBJECT =SUBJID TYPE=UN GROUP= TRTPN; 
  LSMEANS TRTPN / at AWK = 52 PDIFF CL;  
  ODS OUTPUT LSMEANS=MIXLSMNS DIFFS=MISDIFS; 
RUN;     


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(Note: ItemAgrp denotes the categorical Item A (or PUL entry) scores at baseline) 
6.6.1.2. 
Sensitivity Analyses of the Primary Endpoint 
6.6.1.2.1. MMRM Analysis for Primary Efficacy Endpoint 
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 Strategy 
Same as Section 6.6.1.1.3.  
6.6.1.2.1.4. Analysis Variable 
Same as Section 6.6.1.1.4.  
6.6.1.2.1.5. Population Summary for Treatment Comparison  
All post-baseline visits during the double-blind period will be included in the analysis. Change 
from baseline for the specified endpoints (excluding baseline visits) will be analyzed using a 
Mixed Model for Repeated Measures (MMRM) approach with fixed effects for treatment, visit (as 
a factor), treatment-by-visit interaction, and covariates (baseline values). The covariance structure 
strategy is the same as described in Section 6.6.1.1.5.   
Sample SAS code: 
PROC MIXED DATA = XXX;  
  CLASS TRTPN SUBJID AVISITN ItemAgrp;   
  MODEL CHG = TRTPN AVISITN TRTPN* AVISITN ItemAgrp / DDFM=KR; 
  REPEATED AVISITN / SUBJECT =SUBJID TYPE=UN GROUP= TRTPN; 
  LSMEANS TRTPN / at AVISITN = 52 PDIFF CL;  
  ODS OUTPUT LSMEANS=MIXLSMNS DIFFS=MISDIFS; 
RUN;     
6.6.1.2.2. ITT for Primary Efficacy Endpoint 
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 
ITT population will be used as defined in Section 5.2.1.  
6.6.1.2.2.3. Intercurrent Event Handling Strategy 
Same as Section 6.6.1.1.3.  


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6.6.1.2.2.4. Analysis Variable 
Same as Section 6.6.1.1.4.  
6.6.1.2.2.5. Population Summary for Treatment Comparison 
Same as Section 6.6.1.1.5.  
6.6.1.2.3. 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. 
6.6.1.2.3.1. 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  
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. 
6.6.1.2.3.4. Analysis Variable 
Same as Section 6.6.1.1.4 (Missing value imputation rules are defined below). 
6.6.1.2.3.5. Population Summary for Treatment Comparison  
The combined treatment difference of LSMean (and SE) and the corresponding 95% CI for the 
estimated change from baseline in PUL total score at Week 52 will be presented. 
Analysis will be performed in 3 steps. 
Step 1a - First, the intermittent missing PUL 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 PUL and other baseline factors, and the available 
non-missing PUL 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. 
 
Step 1b - Then, for each of the 200 datasets with monotone missing data generated above, missing 
data at end through Week 52 will be imputed to derive 200 imputed datasets with non-missing data. 
Sample SAS code: 
/*examine missing patterns*/ 


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PROC MI DATA = INDAT NIMPUTE = 0;  
 
BY TRTPN; 
     VAR BASE WEEK16 WEEK28 WEEK40 WEEK52; 
RUN; 
Suppose the output from PROC MI above indicates that the missing pattern is non-monotone, it is 
necessary to perform Step 1a, which is Partial imputation (just enough to get the monotone missing 
pattern).  
/*partial imputation to get monotone missing pattern*/  
PROC MI DATA= INDAT OUT=xx1 SEED=9978991 NIMPUTE=200 OUT = MONO; 
 
BY TRTPN; 
 
VAR BASE WEEK16 WEEK28 WEEK40 WEEK52; 
 
MCMC CHAIN=multiple IMPUTE=monotone; 
RUN; 
/*The above procedure will output MONO dataset with a monotone missing data pattern. */ 
PROC SORT DATA= MONO OUT =XX1; 
 
BY _IMPUTATION_; 
RUN; 
 
PROC MI DATA=XX1 OUT=XX SEED=9978 NIMPUTE=1; 
 
BY _IMPUTATION_; 
 
VAR TRTPN BASE WEEK16 WEEK28 WEEK40 WEEK52; 
 
CLASS TRTPN; 
 
MONOTONE REGRESSION (/details); 
RUN; 
 
DATA MIANCOVA; 
 
SET XX; 
 
CHG_WK52= WEEK52 - BASE; 
RUN; 
Step 2 - The 200 multiple-imputation datasets with imputed and observed PUL data at Week 52 
will be analyzed separately for each imputation using the ANCOVA method. The ANCOVA 
model will contain terms for treatment, baseline PUL measurements. The LSMean and 
corresponding SE for the change from baseline in PUL total score at Week 52 will be estimated. 
Sample SAS code: 
PROC MIXED data= MIANCOVA; 
 
BY _IMPUTATION_ 
 
CLASS TRTPN ItemAgrp; 
MODEL CHG_WK52 = TRTPN ItemAgrp COVARIATES/SOLUTION DDFM=KR; 
 
LSMEANS TRTPN / PDIFF CL; 
 
ODS OUTPUT DIFFS=LSDIFS LSMEANS=LSM SOLUTIONF=PARMS; 
RUN; 
Step 3 - The SAS PROC MIANALYZE will be used to derive the final estimates and test statistics 
summarizing the 200 analysis results. 


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Sample SAS code: 
PROC SORT DATA=LSM; 
 
BY TRTPN; 
RUN; 
 
PROC MIANALYZE DATA=LSM; 
 
BY TRTPN; 
 
MODELEFFECTS ESTIMATE; 
 
STDERR; 
 
ODS OUTPUT ParameterEstimates=LSM2; 
RUN; 
 
PROC MIANALYZE DATA= LSDIFS; 
 
MODELEFFECTS ESTIMATE; 
 
STDERR; 
 
ODS OUTPUT ParameterEstimates=lsdiffs2; 
RUN; 
 
 
6.6.1.2.4. 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).  
6.6.1.2.4.1. Estimand Strategy 
Same as Section 6.6.1.1.1 
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  
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. 
6.6.1.2.4.4. Analysis Variable 
Change from baseline in the total score of all PUL assessments at Week 52 (Missing value 
imputation rules are defined below). 


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6.6.1.2.4.5. Population summary for treatment comparison 
Under the jump-to-control assumption, the analysis will be carried out in 3 steps. 
Step 1 - the missing PUL data will be imputed to derive 200 imputed datasets with non-missing data 
according to the jump-to-control data pattern. 
Sample SAS code: 
PROC MI DATA=aval OUT=xx SEED=8767892 NIMPUTE=200; 
 
CLASS TRTP; 
 
VAR BASE WEEK16 WEEK28 WEEK40 WEEK52; 
 
MONOTONE REG(/details); 
 
MNAR MODEL (WEEK52/MODELOBS=(TRTP='Placebo')); 
RUN; 
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 6.6.1.2.3.5.  The 
LSMean and corresponding SE for the change from baseline in PUL total score at Week 52 will be 
estimated. 
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 LSMean, corresponding SE and 95% CI for the estimated 
change from baseline in PUL total score at week 52 will be presented. 
6.6.1.2.5. Pattern Mixture Models under MNAR for Missing Data: Delta-Adjusting (Tipping 
Point) Analysis 
6.6.1.2.5.1. Estimand Strategy 
Same as Section 6.6.1.1.1 
6.6.1.2.5.2. Population of Interest 
Same as Section 6.6.1.1.2  
6.6.1.2.5.3. 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. 
6.6.1.2.5.4. Analysis Variable 
Change from baseline in the total score of all PUL assessments at Week 52 (Missing value 
imputation rules are defined below). 


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6.6.1.2.5.5. Population summary for treatment comparison 
The integrated treatment difference of LSMean, corresponding SE and 95% CI for the change from 
baseline in PUL total score at week 52 will be presented. 
The multiple imputation analysis will be performed as follows. 
Step 1 - the missing PUL data will be imputed to derive 200 imputed datasets with non-missing data 
according to the delta-adjusting data approach. 
Sample SAS code:  
PROC MI DATA=aval OUT=zz SEED=9876783 NIMPUTE=200; 
 
CLASS TRTP; 
 
VAR TRTP BASE WEEK16 WEEK28 WEEK40 WEEK52; 
 
MONOTONE REG; 
 
MNAR ADJUST (WEEK16 /SHIFT=-#.# ADJUSTOBS =(TRTP='pamrevlumab')); 
MNAR ADJUST (WEEK28 /SHIFT=-#.# ADJUSTOBS =(TRTP='pamrevlumab')); 
MNAR ADJUST (WEEK40 /SHIFT=-#.# ADJUSTOBS =(TRTP='pamrevlumab')); 
MNAR ADJUST (WEEK52 /SHIFT=-#.# ADJUSTOBS =(TRTP='pamrevlumab')); 
RUN; 
Step 2- The observed and imputed PUL data will be analyzed using the ANCOVA method 
separately as described in Section 6.6.1.2.3.5 for each of the 200 imputed datasets. The LSMean 
and corresponding SE for the change from baseline in PUL at week 52 will be estimated. 
Step 3- The SAS PROC MIANALYZE will be used to summarize the final estimates and test 
statistics from the 200 dataset results. 
6.6.1.2.6. On-treatment Analysis for Primary Efficacy Endpoint  
A sensitivity analysis will be performed for PUL assessed during on-treatment period as defined in 
Section 5.3.1.2. 
6.6.1.2.6.1. Estimand Strategy 
Same as Section 6.6.1.1.1 
6.6.1.2.6.2. Population of Interest 
Same as Section 6.6.1.1.2  
6.6.1.2.6.3. Intercurrent Event Handling Strategy 
Same as Section 6.6.1.1.3 
6.6.1.2.6.4. Analysis Variable 
Only on-treatment PUL assessments will be included in the analysis 
6.6.1.2.6.5. Population Summary for Treatment Comparison  
If linear assumption was met, the RCM linear regression model as described in Section 6.6.1.1.5 
will be performed; otherwise, ANCOVA model as described in Section 6.6.1.2.3.5 will be 
performed.  


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6.6.1.2.7. Per-Protocol Set Analysis for Primary Efficacy Endpoint 
6.6.1.2.7.1. Estimand Strategy 
Same as Section 6.6.1.1.1. 
6.6.1.2.7.2. Population of Interest 
PPS as defined in Section 5.2.3.  
6.6.1.2.7.3. Intercurrent Event Handling Strategy 
Same as Section 6.6.1.1.3. 
6.6.1.2.7.4. Analysis Variable 
Same as Section 6.6.1.1.4.  
6.6.1.2.7.5. Population Summary for Treatment Comparison  
If the linear assumption was met, the RCM linear regression model as described in 
Section 6.6.1.1.5 will be performed; otherwise, the ANCOVA model as described in 
Section 6.6.1.2.3.5 will be performed.  
 
6.6.1.2.8. Cumulative Loss of Function Analysis for Primary Efficacy Endpoint 
This sensitivity analysis will use data representing cumulative failure to perform 22 items of PUL 
2.0 in patients at multiple time points over 52 weeks.  
6.6.1.2.8.1. Estimand Strategy 
Failure to perform an item is defined as a score transition from 2 or 1 to 0 at evaluation. Only post-
baseline failures will be considered in this 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) [17] 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 the assumption of constant ratio is not plausible, the resulting estimate reflects an 
averaged ratio between the two curves over time. The lower the ratio (Pamrevlumab over Placebo), 
the greater the treatment effect.  
6.6.1.2.8.2. Population of Interest 
Same as Section 6.6.1.1.2  


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6.6.1.2.8.3. Intercurrent Event Handling Strategy 
If a patient discontinued, the cumulative failure number will be censored upon discontinuation. 
6.6.1.2.8.4. Analysis Variable 
Cumulative counts of failure to perform 22 items of PUL 2.0 at each protocol specified timepoint. 
6.6.1.2.8.5. 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 22 items of PUL 2.0 at post-baseline visits will be analyzed using the 
LWYY analytic method to estimate the ratio between treatment arms. Rate ratio between 2 
treatment 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 SUBJID; 
   WHERE TSTART < TSTOP; 
RUN; 
Note: 1= censored. For more information, please refer to SAS online help. 
6.6.2. 
Secondary Endpoint 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. 
Continuous Secondary Endpoints with RCM Model 
6.6.2.1.1.1. Estimand Strategy 
Same as Section 6.6.1.1.1 
6.6.2.1.1.2. Population of Interest 
Same as Section 6.6.1.1.2  
6.6.2.1.1.3. Intercurrent Event Handling Strategy 
Same as Section 6.6.1.1.3  
6.6.2.1.2. Analysis Variables 
6.6.2.1.2.1. Change in Percent Predicted Forced Vital Capacity (ppFVC) from baseline to 
Week 52, assessed by spirometry 
6.6.2.1.3. Change in the total score of Mid-level of PUL from baseline to Week 52Population 
Summary for Treatment Comparison  
Same as Section 6.6.1.1.5. 
 


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6.6.2.2. 
Continuous Secondary Endpoints with MMRM Model 
6.6.2.2.1.1. Estimand Strategy 
Same as Section 6.6.1.1.1 
6.6.2.2.1.2. Population of Interest 
Same as Section 6.6.1.1.2  
6.6.2.2.1.3. Intercurrent Event Handling Strategy 
Same as Section 6.6.1.1.3  
6.6.2.2.2. Analysis Variables 
6.6.2.2.2.1. Absolute Change from Baseline in Grip Strength at Week 52 
The absolute change from baseline in the grip strength of the hands is derived with the formula 
below: 
𝑔𝑔𝑔𝑔𝑔𝑔𝑔𝑔 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠ℎ 𝑜𝑜𝑜𝑜 𝑡𝑡ℎ𝑒𝑒 ℎ𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣
−𝑔𝑔𝑔𝑔𝑔𝑔𝑔𝑔 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠ℎ 𝑜𝑜𝑜𝑜 𝑡𝑡ℎ𝑒𝑒 ℎ𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑎𝑎𝑎𝑎 𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵 
The grip strength should be reported by dominant and non-dominant hand separately. 
6.6.2.2.3. Covariance Structure Strategy 
The unstructured covariance structure for the within-patient errors in the model will be applied 
first. The by-treatment-group option may will be added to the covariance pattern to improve the 
model fit as appropriate. 
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, 
until the model converges. The sandwich estimator will be used if there is convergence issue. If the 
model doesn’t 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. 
Sample SAS code: 
/* excluding baseline visit */ 
PROC MIXED DATA=MMRM (WHERE=(AVISITN>0));  
 
CLASS TRTP AVISIT; 
MODEL CHG = TRTP AVISIT TRTP*AVISIT BASE /DDFM=KR; 
 
REPEATED AVISIT /SUBJECT=SUBJID TYPE=UN GROUP=TRTP; 
 
LSMEANS TRTP /PDIFF CL; 
 
LSMEANS TRTP*AVISIT /PDIFF CL; 
ODS OUTPUT LSMEANS=MIXLSMNS DIFFS=MIXDIFS; 
RUN; 


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6.6.2.3. 
Continuous Secondary Endpoints with ANCOVA Model 
6.6.2.3.1.1. Estimand Strategy 
Same as Section 6.6.1.1.1 
6.6.2.3.1.2. Population of Interest 
Same as Section 6.6.1.1.2  
6.6.2.3.1.3. Intercurrent Event Handling Strategy 
Same as Section 6.6.1.1.3  
6.6.2.3.2. Analysis Variables 
6.6.2.3.2.1. Change in Left Ventricular Ejection Fraction Percentage (LVEF %) from 
Baseline to Week 52, Assessed by MRI 
6.6.2.3.3. Population Summary for Treatment Comparison  
The change in the LVEF% from baseline to Week 52 will be analyzed using an ANCOVA model, 
which contains terms for treatment, baseline LVEF measurements. The LSMean and 
corresponding SE for the change from baseline in LVEF at Week 52 will be estimated.   
Sample SAS code: 
/* excluding baseline visit */ 
PROC MIXED DATA=ANCOVA METHOD=ML;  
 
CLASS TRTP; 
MODEL CHG = TRTP BASE / DDFM = KR; 
 
LSMEANS TRTP /PDIFF CL; 
RUN; 
 
6.6.2.4. 
Analysis of A Composite of Endpoints 
6.6.2.4.1.1. Estimand Strategy 
To evaluate the totality of the treatment effect in multiple muscle groups (i.e., skeletal, respiratory, 
and cardiac muscle), a composite endpoint will be used to combine the results from multiple 
outcomes including primary endpoint and 3 key secondary endpoints (PUL, ppFVC, Grip Strength, 
LVEF%) as a secondary analysis following the method introduced by Li, et al in 2020. 
6.6.2.4.1.2. Population of Interest 
Same as Section 6.6.1.1.2  
6.6.2.4.1.3. Intercurrent Event Handling Strategy 
Same as Section 6.6.1.1.3  


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6.6.2.4.2. Analysis Variables 
The z-score is defined as LSmean of the treatment difference divided by its corresponding SE at 
week 52 from the primary analysis model. The mean z-score will be calculated sequentially across 
4 endpoints (PUL, ppFVC, Grip Strength, LVEF%), namely, the mean z-scores for PUL + ppFVC, 
PUL + ppFVC + Grip Strength, PUL + ppFVC + Grip Strength + LVEF will be reported. 
6.6.2.4.3. Population Summary for Treatment Comparison  
The mean z-score will be calculated sequentially across 4 endpoints (PUL, ppFVC, Grip Strength, 
LVEF%) and p-value will be derived by a permutation method to rerandomize patient vectors of 
the observed values from the 4 endpoints in 1000 trials. A distribution of the mean z-score will be 
derived from these 1000 trials. A p-value will be computed from the z-score from this clinical trial 
against the backdrop of the random distribution of the 1000-trial z-scores. p-values corresponding 
to the z-scores for PUL + ppFVC, PUL + ppFVC + Grip Strength, PUL + ppFVC + Grip Strength 
+ LVEF will be reported. If the p-value is < 0.025 (1-sided), the composite endpoint is deemed to 
be statistically significant. 
The method was introduced by Li, et al in 2020 [16].   
6.6.2.5. 
Assessments by ITT populations of secondary endpoints: 
Assessments by ITT populations of secondary endpoints will be considered as sensitivity analysis 
for these secondary endpoints. Summary of the following endpoints will also be conducted on the 
ITT population. The change from baseline to Week 52 in these endpoints will be summarized by 
analysis visit and analyzed using the RCM or MMRM or ANCOVA model as described in 
corresponding sections in Section 6.6.2 . 
• Change in percent predicted forced vital capacity (ppFVC) from baseline to Week 52, 
assessed by spirometry 
• Change in the total score of Mid-level of PUL from baseline to Week 52 
• Change in the Grip strength of the hands from baseline to Week 52, assessed by 
Handheld Myometry (HHM) 
• Change in Left Ventricular Ejection Fraction percentage (LVEF %) from baseline to 
Week 52, assessed by MRI 
• Sequential composites of endpoints - PUL + ppFVC, PUL + ppFVC + Grip Strength, 
PUL + ppFVC + Grip Strength + LVEF 
 
6.6.3. 
Exploratory Analyses 
6.6.3.1. 
Change in the Subscores of Regional Dimensions (High-level (Shoulder), Distal-
level (Wrist and Hand)) of PUL, from Baseline to Week 52 
Summary of the listings and analyses of subscores of regional dimensions (High-level (shoulder), 
Distal-level (wrist and hand)) of PUL will be summarized for subjects in the ITT population. 


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The change from baseline to Week 52 in subscores of regional dimensions (High-level (shoulder), 
Distal-level (wrist and hand)) of PUL, will be analyzed using the same analysis method as the one 
for the primary endpoint. 
6.6.3.2. 
Change in Duchenne Video Assessment Severity Percentage from Baseline to 
Week 52 
The Duchenne Video Assessment (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 CGI-C 
scores will be based on the ITT population. The change from baseline to Week 52 in Duchenne 
Video Assessment severity percentage will be summarized by analysis visit and analyzed using the 
MMRM model as described above.  
The CGI-C will be analyzed using the proportional odds model, a special case of generalized linear 
mixed models (GLMM). The GLMM model will include treatment as fixed effect. The model will 
be fitted using GLMM with a multinomial distribution and a cumulative logit link function.  The 
proportional odds ratio estimate between Pamrevlumab and placebo, the corresponding 95% CI 
and P-value will be presented. If the proportional odds assumption is contradicted (p < 0.05 in 
Score Test for the Proportional Odds Assumption) by the observed data, the GLMM method will 
be replaced by the nonparametric van Elteren test to test whether there is a difference in the 
location of distribution of the CGI-C at 52 weeks between Pamrevlumab and placebo. 
6.6.3.3. 
Change in Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) 
from Baseline to Week 52 
Standardized PFTs including FVC, PEF, FEV1 will be collected for consistency during the course 
of the study. The PFT vendor will provide the SpiroSphere®. Within a PFT session, eight attempts 
may be made. Only sessions with Best Test Read (BTR) grade of borderline or acceptable are 
considered valid. The session may be repeated up to three times during the screening window. The 
Day 1 PFT session may also be repeated up to three times. If sessions are repeated, the last session 
conducted for screening, and the last session conducted for Day 1 supersede all others and are used 
to determine the average for baseline. 
Summary of the listings and analyses percent predicted forced expiratory volume at 1 second 
(ppFEV1) will be based on the ITT population. The change from baseline to Week 52 in ppFEV1 
will be summarized by analysis visit and analyzed using the RCM model as described above. 
6.6.3.4. 
Change in percent predicted peak expiratory flow (ppPEF) from baseline to Week 
52, assessed by spirometry 
The change from baseline to Week 52 in ppPEF between two treatment arms will be summarized 
by analysis visit and analyzed using the RCM model as described above. 


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6.6.3.5. 
Analysis of Progression of Dilated Cardiomyopathy (DCM) by genetic analysis 
A whole blood sample will be collected in a PAXgene blood DNA tube for DNA analysis on Day 
1 before dosing for all subjects who agree to DNA analysis (to include but not limited to LTBP4 & 
SPP1). This testing is optional, requires specific consent by participating subjects and subjects may 
refuse DNA testing. In the event that a subject later agrees to genetic testing, a blood sample may 
be collected as an unscheduled lab draw. Only tests for genetic loci associated with dilated 
cardiomyopathy (DCM) will be performed and all samples will be destroyed after testing is 
completed. 
Summary of the progression of dilated cardiomyopathy (DCM) by genetic analysis will be based 
on the ITT population. Proportion of patients with progression of dilated cardiomyopathy (DCM) 
will be summarized.   
6.6.3.6. 
Fibrosis/MRI assessments:  
6.6.3.6.1. Changes in Fibrosis Score of the Biceps Brachii from Baseline to Week 52, 
Assessed by MRI  
Summary of the listings and analyses of upper arm (bicep) muscle fibrosis assessed by MRI, will 
be summarized based on ITT population. 
The change from baseline to Week 52 in fibrosis score of the biceps brachii muscle assessed by 
MRI between two treatment arms will be compared by ANCOVA. The ANCOVA model will 
contain terms for treatment and baseline measurements. 
6.6.3.6.2. Changes in Cardiac Fibrosis Score from Baseline to Week 52, Assessed by Late 
Gadolinium Enhancement (LGE).  
Summary of the listings and analyses of changes in cardiac fibrosis (LGE) will be based on the ITT 
population.  
The change from baseline to Week 52 in cardiac fibrosis score assessed by MRI and Mass of Late 
Gadolinium Enhancement (Scar Mass) between two treatment arms, will be compared by 
ANCOVA. The ANCOVA model will contain terms for treatment and baseline measurements. 
In addition, dichotomous responder analysis (proportion of patients with change from baseline in 
cardiac fibrosis score ≥ 0 at Week 52) will be summarized and analyzed. The logistic regression 
model will be used to compare the proportion of subjects with change from baseline in cardiac 
fibrosis >=0. The model will include treatment and baseline cardiac fibrosis score. 
6.6.3.7. 
Change in Myocardial Circumferential Strain [Global Circumferential Strain 
(GCS)%] percentage from Baseline to Week 52, Assessed by cardiac MRI.  
Summary of the listings and analyses of annual changes from baseline for the Global Myocardial 
Circumferential Strain (GCS) will be summarized for subjects in the ITT population,  
The change from baseline to Week 52 in GCS score between two treatment arms will be compared 
by ANCOVA. The ANCOVA model will contain terms for treatment and baseline measurements. 
In addition, dichotomous responder analysis (proportion of patients with change from baseline in 
GSC score ≥ 0 at Week 52) will be summarized and analyzed. The logistic regression model will 


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be used to compare the proportion of subjects with change from baseline in GCS score >=0. The 
model will include treatment and baseline cardiac fibrosis score. 
6.6.4. 
Subgroup Analyses of Specified Endpoints 
The subgroups may include but are not limited to,  
• Age group (<=16 years, >16 years),  
• Race (White, Others),  
• Corticosteroids use (Deflazacort, Prednisone/Prednisolone).  
• Baseline PUL level (<= Median, > Median) 
• Baseline PUL entry Item A score (=1, >1) 
• Baseline PUL entry Item A score (2-5, 1 or 6) 
• Regional subgroups: 
− US, Non-US 
− China, Non-China  
The primary endpoint PUL will be repeated for relevant and appropriate subgroups. If linear 
assumption was met, the RCM linear regression model as described in Section 6.6.1.1 will be 
performed for subgroup analysis; otherwise, MMRM model as described in Section 6.6.1.2.1 will 
be performed. Secondary endpoints ppFVC, Mid-level of PUL, grip strength, and LVEF will also 
be analyzed by subgroups. 
If 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. 
The LSMean of treatment difference and corresponding 95% CI will be presented in a forest plot. 
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 26.0 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 treatment emergent adverse event (TEAE). Partially 
or incomplete missing AE start/stop date/time will be imputed (Appendix 1 ). 
If more than one event occurs with the same system organ class (SOC) and preferred term (PT) for 
the same patient, the patient will be counted only once for that preferred term using the most severe 
and most related occurrence for the summarization by common terminology criteria for adverse 
events (CTCAE) severity grade and by relationship to the study medication. Relationship to study 
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The following summary AE tables including number (%) of subjects will be produced: 
• Summary of all AEs 
• TEAEs by PT 
• TEAEs by SOC and PT 
• TEAEs by SOC, PT, and maximum severity 
• TEAEs 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 
• Ulna length measurements for indirect measure of growth velocity (cm/year) for subjects 
under the age of 18 (Refer to Section 6.8.7 ) 
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  


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WBCs (Leukocyte count)  
ALP  
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. 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 data 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 (24 hours: on day of infusion or 1 day post any study drug infusion) 
3. Anaphylactic reactions (24 hours: 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, and subgroups (same as TEAEs). 
Items 3 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. 
Growth Velocity (cm/year) 
Ulna length measurements is used for indirect measure of annualized growth velocity (cm/year) for 
subjects under the age of 18. For subjects that enter the study at age 18 or turn 18 during the study, 
the last recorded ulna length/height will be used for the remainder of the study. 


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Annualized growth velocity (cm/year) is defined to be the ratio of change in height (cm) between 
the baseline and post-baseline to the duration of the observed time (years), where height is 
estimated by the formula described in Section 6.3.1. 
6.8.8. 
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 
− 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. 
 
6.8.9. 
Subgroup Analyses of Safety Endpoints 
The subgroup analysis will be conducted to safety endpoints such as TEAE and TESAE. The 
subgroups are specified in Section 6.6.4, not including subgroup defined by Baseline PUL level.  
 
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 
A listing will include all available Human Anti-Human Antibody (HAHA, ADA) samples will be 
provided. ADA analysis will be conducted in the OLE phase of the study.  


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7. 
CHANGES FROM PROTOCOL 
• Changes for the primary analysis: 
The mITT population is defined in Section 5.2.2 and is used for the analysis of primary 
and secondary efficacy endpoints. In addition, sensitivity analyses will be conducted for 
the primary and secondary efficacy endpoints in the ITT population. 
 
• Rationale for the changes: 
• Recently published observational data suggest that patients with PUL 2.0 entry 
score 1 have minimal PUL 2.0 changes over a one-year treatment period [19]. 
Consequently, there is no meaningful opportunity to demonstrate the benefit of a 
therapeutic drug in the PUL 2.0 entry score 1 subpopulation. This information was 
published in April, 2023, after the study was already designed. 
• This is the largest observational study of PUL 2.0 scores to date in 311 patients 
followed longitudinally over 24 months with 808 paired assessments [19]. In this 
study, the decline of PUL 2.0 scores for patients with a PUL 2.0 entry score of 1 
was very low at 12 and 24 months compared to patients with higher PUL 2.0 entry 
scores.  For example:  
• At 12 months, the mean PUL 2.0 total score change on all the paired 
assessments for patients with PUL 2.0 entry scores of 1 was -0.84 
compared to -2.05 for PUL 2.0 entry score of 3. Changes were even 
greater for patients with PUL entry scores of 4, 5, or 6. 
 • At 24 months, the mean PUL 2.0 total score change on all the paired 
assessment for patients with PUL 2.0 entry scores of 1 was -1.78 
compared to -3.82 for patients with PUL 2.0 entry score of 3. Changes 
were even greater for patients with PUL 2.0 entry scores of 4, 5, or 6.  
• Based on these results, the authors concluded that differences in PUL 2.0 entry 
scores should be taken into account when designing and analyzing clinical studies 
[19] and this supports the proposed change to the analysis population to exclude 
patients with a PUL baseline score of 1. 
• Based on these results, the authors concluded that differences in PUL 2.0 entry 
scores should be taken into account when designing and analyzing clinical studies 
[19].  
• In an early study by Pane from a cohort of 187 patients with DMD, which included 
90 non-ambulatory patients, patients with the lowest PUL entry scores of 0 or 1 had 
minimal further progression during a 12-month follow-up period.   
• Expert guidance from key opinion leaders for PUL 2.0 
 
 strongly support the approach of removal of patients with 
PUL 2.0 entry scores of 1 because these patients do not demonstrate significant 
decline over a 1-year period and therefore impact meaningful opportunity to 
demonstrate efficacy. 


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• Based on changes in the external environment for DMD studies, the Sponsor 
conduced an analysis of current trials from clinicaltrials.gov and concluded that 
other clinical trials in the non-ambulatory DMD patient population using the PUL 
2.0 as a primary endpoint measure have excluded patients with a PUL 2.0 entry 
score of 1 at baseline.  For example, Capricor Inc./NCT05126758 A Phase 3, 
Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and 
Safety of Human Allogeneic Cardiosphere-Derived Cells for the Treatment of 
Duchenne Muscular Dystrophy A Study of CAP-1002 in Ambulatory and Non-
Ambulatory Patients with Duchenne Muscular Dystrophy (HOPE-3). 
• Non-ambulatory DMD patients have limited treatment options and have been 
excluded from clinical trials in emerging treatment classes. Modification of the 
analysis will result in benefit to non-ambulatory patients as well as increased 
treatment options. 
• The Sponsor has determined that removal of patients with a baseline PUL 2.0 entry 
score of 1.0 will result in approximately 15 patients removed from the ITT 
population. The sample size and power calculations are based on the assumptions 
described in the protocol, and with 15 fewer subjects out of 97 dosed subjects, the 
trial will have 87% power with 82 subjects in the mITT population. 
 
• Sample size calculation was updated per the latest literature publications and study 
enrollment. The testing sequence of secondary endpoints was changed from the 
protocol. 
• Changed the analysis method for subscores of regional dimensions (High-level 
(Shoulder), Distal-level (Wrist and Hand)) of PUL from MMRM to RCM, the same one 
used in the primary analysis.  
• The analysis methods for change from baseline at week 52 in LVEF, Fibrosis Score of 
the Biceps Brachii, Cardiac Fibrosis Score, Myocardial Circumferential Strain [Global 
Circumferential Strain (GCS)%] percentage are changed from MMRM to ANCOVA 
respectively, because there are only two assessments performed during the study for 
these exploratory endpoints – one at baseline and the other at week 52 and it is not 
suitable for mixed models of repeated measures.  
• MMRM (Section 6.6.1.2.1 ), Cumulative Loss of Function Analysis (Section 6.6.1.2.8 ) 
are added as sensitivity analyses for the primary efficacy endpoint. 
• Added the composite of endpoints - mean observed z scores sequentially across 4 
endpoints (PUL, ppFVC, Grip Strength, LVEF%) at week 52, namely, the mean z-
scores for PUL + ppFVC, PUL + ppFVC + Grip Strength, PUL + ppFVC + Grip 
Strength + LVEF% , to the secondary endpoint. Analysis with the Composite of 
Endpoints (Section 6.6.2.4 ) is added as additional analysis for PUL. 
• Change in the total score of Mid-level of PUL from baseline to Week 52 is added as a 
secondary endpoint. 
 


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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. Pane M, Mazzone ES, Fanelli L, et al. Reliability of the Performance of Upper Limb 
assessment in Duchenne muscular dystrophy. NeuromuscDisord 2014;24:201-206. 
3. Mayer OH, Finkel RS, Rummey C et al.  Characterization of Pulmonary Function in 
Duchenne Muscular Dystrophy. PediatrPulmonol. 2015; 50:487–494 
4. J. Finder et al. Pulmonary Endpoints in Duchenne Muscular Dystrophy A Workshop 
Summary Am J Respir Crit Care Med Vol 196, Iss 4, pp 512–519, Aug 15, 2017 
5. S. C. Hagenbuch et al. Detection of Progressive Cardiac Dysfunction by Serial Evaluation 
of Circumferential Strain in Patients With Duchenne Muscular Dystrophy Am J 
Cardiology, 2010;105:1451–1455 
6. 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, Neuromuscular Disorders (2019) 1-8. 
7. Seferian, et al. 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):1-18. 
8. 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. 
9. 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 
10. 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.  
11. 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  
12. Szigyarto CA, Spitali P. (2018) Biomarkers of Duchenne muscular dystrophy: current 
findings. Degener Neurol Neuromuscul Dis. 8:1-13 
13. Yiu EM, Kornberg AJ. (2015) Duchenne muscular dystrophy. J Pediatric Child Health. 
51(8):759-764.  
14. Zhou L, Lu H. (2010) Targeting fibrosis in Duchenne muscular dystrophy. J Neuropathol 
Exp Neurol. 69(8):771-776. 
15. McDonald Craig, et al. (2021) Evaluating longitudinal therapy effects via the North Star 
Ambulatory Assessment. Muscle & Nerve. DOI: 10.1002/mus.27396 


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16. Daniel Li, et al. (2020) Assessment of Treatment Effect With Multiple Outcomes in 2 
Clinical Trials of Patients With Duchenne Muscular Dystrophy. JAMA Network Open. 
2020;3(2):e1921306. DOI:10.1001/jamanetworkopen.2019.21306 
17. D. Y. Lin, et al. (1999) Semiparametric regression for the mean and rate functions of 
recurrent events, J. R. Statist. Soc. B (2000) 62, Part 4, pp. 711-730 
18. China National Medical Products Administration, Technical Guidance for Accepting 
Overseas Clinical Trial Data ([2018] No.52), 2018 
19. Pane, Marika et al. ‘Longitudinal Analysis of PUL 2.0 Domains in Ambulant and Non-
Ambulant Duchenne Muscular Dystrophy Patients: How Do They Change in Relation to 
Functional Ability?’ Journal of Neuromuscular Diseases, vol. Pre-press, no. Pre-press, pp. 
1-8, 2023. 
20. Astellas Pharma Inc. A Randomized, Double Blind, Placebo-Controlled Phase 1b Study 
With Open-Label Extension to Assess the Safety, Tolerability and Preliminary Efficacy of 
ASP0367 (MA-0211) in Pediatric Male Patients With Duchenne Muscular Dystrophy 
(DMD). ClinicalTrials.gov identifier NCT04184882. 
21. Capricor. A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With 
Duchenne Muscular Dystrophy. ClinicalTrials.gov identifier NCT05126758. Updated May 
3, 2023. Accessed May 8, 2023.  
https://clinicaltrials.gov/ct2/show/NCT05126758. 
22. Capricor. A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the 
Safety and Efficacy of Intravenous Delivery of Allogeneic Cardiosphere-Derived Cells in 
Subjects with Duchenne Muscular Dystrophy. ClinicalTrials.gov identifier NCT03406780. 
23. Dyne Therapeutics. A Randomized, Double-Blind, Placebo-Controlled, Multiple 
Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and 
Pharmacokinetics of DYNE-251 Administered to Participants With Duchenne Muscular 
Dystrophy Amenable to Exon 51 Skipping. ClinicalTrials.gov identifier NCT05524883. 
24. McDonald et al (2022). Repeated intravenous cardiosphere-derived cell therapy in late- 
stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, 
placebo-controlled, phase 2 trial. The Lancet, Volume 399, Issue 10329,2022,Pages 1049-
1058,ISSN 0140-6736,https://doi.org/10.1016/S0140-6736(22)00012-5. 
25. McDonald CM, Gordish-Dressman H, Henricson EK, Duong T, et al. Longitudinal 
pulmonary function testing outcome measures in Duchenne muscular dystrophy: Long- 
term natural history with and without glucocorticoids. Neuromuscular Disorders, Volume 
28, Issue 11,2018. Pages 897-909. ISSN 0960-8966. 
https://doi.org/10.1016/j.nmd.2018.07.004. 
26. Pane M, Coratti G, Brogna C, Mazzone ES, Mayhew A, et al. (2018) Upper limb function 
in Duchenne muscular dystrophy: 24 month longitudinal data. PLOS ONE 13(6): 
e0199223.  
https://doi.org/10.1371/journal.pone.0199223 


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27. Pfizer. A Phase 1b Multicenter, Open-Label, Single Ascending Dose Study to Evaluate the 
Safety and Tolerability of Pf-06939926 in Ambulatory and Non-Ambulatory Subjects with 
Duchenne Muscular Dystrophy. ClinicalTrials.gov identifier NCT03362502. 


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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. 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 52 of 68 
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). 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 53 of 68 
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. 
 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 54 of 68 
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 
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 8: 
Analysis Visit Window for Pulmonary Function Tests (PFT) 
 
Analysis Visit 
Target Day 
Start Day 
End Day 
Baseline 
See Section 5.3.2  
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 16 
113 
2 
155 
Week 28 
197 
156 
239 
Week 40 
281 
240 
323 
Week 52 
365 
324 
** 
** 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. 
 
 
 
 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 55 of 68 
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. 
 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 56 of 68 
APPENDIX 3. PERFORMANCE OF THE UPPER LIMB (PUL) MODULE  
 
 
High level shoulder Dimension:   Administer only if subject scored  3, 4, 5, 6 on item 
A 
Item 
Description 
0 
1 
2 
1 
Score 
from 
Entry 
item 
above 
Shoulder abduction 
both arms above 
head 
“Raise your arms 
above your head out 
to the side – try and 
keep straight 
elbows” 
Unable 
Can raise both 
arms 
simultaneously 
above head 
only by flexing 
the elbow - with 
compensation 
Can abduct both 
arms 
simultaneously 
elbows in extension 
in a full circle until 
they touch above 
the head 
Performance of the Upper Limb Module for DMD 2.0 (PUL for DMD) 
Dominant arm (used for all tests):    ☐ Right      ☐ Left                                                     
Elbow extension ROM full = 0°: Right:                  Left: 
e.g. 10° contracture = -10° 
Supination ROM: Right:      ☐ Full   ☐ ¾     ☐½     ☐¼       Left:  ☐ Full   ☐ ¾     ☐½    
☐¼ 
Entry item A. – start with A to identify starting point for subsequent tests. Circle score 
for each item. DO NOT INCLUDE IN TOTAL SCORE 
Item 
Score 
Description 
A 
0 
No useful function of hands 
 
1 
Can use hands to hold pen or pick up a coin or drive a 
powered chair 
 
2 
Can raise 1 or 2 hands to mouth but cannot raise a cup with a 
200g weight in it to mouth 
 
3 
Can raise plastic cup with 200g weight in it to mouth using 1 
or 2 hands 
 
4 
Can raise both arms (to shoulder height with or without 
compensation), i.e.  elbow bent or in extension 
 
5 
Can raise both arms simultaneously above head only by 
flexing the elbow (shortening circumference of the movement /using accessory 
muscles) 
 
6 
Can abduct both arms simultaneously elbows in extension in 
a full circle until they touch above the head. 
For item A:   A score of 3, 4, 5, 6 on item A, start with item 1. A score of, 1, 2 start 
with item 7  


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
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Page 57 of 68 
2 
 
Raise both arms to 
shoulder height 
(elbows at shoulder 
height) 
“Raise your arms to 
shoulder level” 
Unable 
Can raise both 
arms to 
shoulder height 
either one at a 
time or with 
elbows flexed 
(with 
compensation) 
Can raise both 
elbows to shoulder 
height without 
compensation 
e.g. simultaneously 
with elbows 
straight 
3 
Shoulder flexion to 
shoulder height (no 
weights) 
“Reach out and 
touch my hand” –
elbow to eye level 
Unable 
Able with 
compensation 
Able without 
compensation 
 
 
4 
Shoulder flexion to 
shoulder height with 
500g weight 
“Reach out and 
touch my hand” –
elbow to eye level 
Unable  
Able to lift 
500g weight 
with 
compensation 
Able to lift 500g 
weight without 
compensation 
5 
Shoulder flexion 
above shoulder 
height with 500 g 
weight  
Hand on lap – “give 
me the weight” 
Unable  
Able to lift 
500g weight 
with 
compensation 
Able to lift 500g 
weight without 
compensation 
6 
 
 
Shoulder flexion 
above shoulder with 
1 kg weight  
Hand on lap – “give 
me the weight” 
Unable  
Able to lift 1 kg 
weight with 
compensation 
Able to lift 1 kg 
weight without 
compensation 
 
Mid-level elbow Dimension 
Do these tests on all individuals 
Item 
Description 
0 
1 
2 
7 
 
Hand(s) to mouth 
“Bring the cup to 
your mouth with 
one hand” 
 
Unable  
Able to bring 200g 
in cup with any 
compensation to 
mouth (can use 
more than one hand 
and / or bring head 
to hands) 
Able to bring 200g 
in cup to mouth 
with one hand no 
elbow support 
(without 
compensation) 
8 
 
Hands to table 
from lap 
“Bring both hands 
from lap to table” 
Unable 
 
Able to bring two 
hands completely 
(to wrist crease) to 
table but NOT 
Two hands 
completely on 
table 
simultaneously 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
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Page 58 of 68 
simultaneously or 
in one action  
9 
 
Move weight on 
table 100g 
“Move the weight 
from outside 
circle to centre 
circle” 
Unable 
Can move 100g 
weight from outer 
to centre circle 
using compensation 
(slide forearm or 
elbow make contact 
with table) 
Can lift 100g 
weight from outer 
to centre circle 
without 
compensation 
10 
Move weight on 
table 500g 
“Move the weight 
from outside 
circle to centre 
circle” 
Unable 
Can move 500g 
weight from outer 
to centre circle 
using compensation 
(slide forearm or 
elbow make contact 
with table) 
Can lift 500g 
weight from outer 
to centre circle 
without 
compensation 
11 
Move weight on 
table 1kg 
“Move the weight 
from outside 
circle to centre 
circle” 
Unable 
Can move 1kg 
weight from outer 
to centre circle 
using compensation 
(slide forearm or 
elbow make contact 
with table) 
Can lift 1kg 
weight from outer 
to centre circle 
without 
compensation 
12 
 
 
Lift heavy can 
diagonally  
“Lift can from 
this circle nearest 
your hand to this 
circle furthest 
away and across 
your body” 
Unable  
Can move heavy 
can from nearest 
circle across body 
with compensation 
(slide forearm or 
elbow make contact 
with table) 
Can lift heavy can 
from nearest circle 
across body 
without 
compensation 
13 
 
 
Stack of three 
cans 
“Stack these two 
cans, one at a 
time on the 
middle can using 
one hand” 
Unable to 
stackthirdca
n even with 
compensatio
n 
 
 
Able to stack third 
can with 
compensation 
 
Able to stack third 
can without 
compensation 
14 
 
 
Stack of five cans 
“Stack these two 
additional cans, 
one at a time on 
top of this can 
using one hand” 
Unable to 
stackfifthca
n even with 
compensatio
n 
 
 
Able to stack fifth 
can with 
compensation 
 
Able to stack fifth 
can without 
compensation 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 59 of 68 
15 
 
Remove lid from 
container  
“Use your hands 
to open this 
container” 
 
Unable  
 
Opens completely  
 
 
 
Distal wrist and hand Dimension: Do these tests on all individuals 
Item 
Description 
0 
1 
2 
16 
Tearing paper 
“Tear the sheet of 
paper beginning 
from here” 
Unable 
Tears the sheet of 
paper folded in half 
from the folded 
edge 
Tears the sheet of 
paper folded in 4, 
beginning from the 
folded edge 
17 
 
Tracing path 
“Use your pencil to 
complete the path in 
one smooth 
movement” 
Unable 
Completes the path 
with compensation 
- needs to raise 
pencil from paper 
or pivot arm 
Able to complete 
the path without 
stops or raising 
hand from paper 
18 
Push on light 
“Push on the light 
with the fingers of 
one hand” 
Unable  
Able to turn the 
light on 
momentarily with 
fingers of one hand  
Able to turn the 
light on 
permanently with 
fingers of one 
hand 
 
19 
Supination  
“Pick up the light 
and turn your hand 
over” 
Unable  
Picks up the light 
but either turns 
hands over 
incompletely or 
uses compensation 
to turn it over 
Picks up the light, 
and turns the hand 
over completely 
with no 
compensatory 
movements 
20 
 
 
Picking up coins  
“Using one hand, 
Pick up 6 coins, one 
at a time”  
Cannot 
pick up 
one coin 
Can pick up one 
coin/ token  
Can pick up six 
coins in one hand  
21 
 
 
Placing finger on 
number diagram 
(precision not 
essential) 
“Using one finger to 
touch each number 
on the diagram” 
Cannot 
raise the 
finger or 
slide it on 
the 
diagram 
Able to place finger 
(slide or lift) 
between at least 
two squares 
Able to place 
finger successively 
on the numbers of 
the diagram   
(with or without 
compensation) 
22 
 
Pick up 10g weight 
finger pinch 
“Pick up this small 
weight like this (by 
body of weight)” 
Unable  
 
 
 Able to grip and 
lift weight off 
surface 
 
 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 60 of 68 
 
 
 
 
Additional Material 
 
Item 17: Tracing a path 
 
 
Item 21: Placing finger on number diagram 
Instruction: Starting on the yellow number 1 point to the numbers 1 to 10 in turn following the 
arrow 
 
 
 
 
 
 
 
Were all tests valid?   
(i.e., representative of child’s true 
function) 
Yes □   No □ 
Total Score PUL     
 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 61 of 68 
If no, which tests 
were invalid? 
 And why? 
 
Hand Held 
Myometry 
□  □ Testing Environment (i.e. equip. malfunction, fire alarm, disruption) 
 
□ General health (i.e. stomachache, cold, flu) 
 
□ Travel delays (i.e. lack of sleep; testing not performed at regular time) 
 
□ Inappropriate clothing  
 
□ Behavior 
□ Musculoskeletal issue (i.e. injury, muscle cramping, tendinitis) 
□ Other (please explain in comment section of worksheet) 
PUL 
□  □ Testing Environment (i.e. equip. malfunction, fire alarm, disruption) 
 
 
□ General health (i.e. stomachache, cold, flu) 
 
 
□ Travel delays (i.e. lack of sleep; testing not performed at regular time) 
 
 
□ Inappropriate clothing o 
 
 
□ Behavior 
□ Musculoskeletal issue (i.e. injury, muscle cramping, tendinitis) 
□ Other (please explain in comment section of worksheet) 
 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 62 of 68 
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 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
Confidential 
Page 63 of 68 
  
  
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 
 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
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Page 64 of 68 
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 SASÒ version 9.4 or greater. 
2. 
General  
All TFLs are based on SDTM and/or 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 11: 
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. 


FGCL-3019-093 (LELANTOS1) 
 
Statistical Analysis Plan, Final v1.0 
 
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Page 65 of 68 
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 : ddMMMyyyy” (right 
aligned) 
second title 
protocol number “Protocol: FGCL-3019-093 (LELANTOS(-1))” (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 12 . 
Table 12: 
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. [18]