Clinical trial NCT02606136
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne muscular dystrophy DMD non-ambulatory
Sponsor: FibroGen
Start date: 2016-01-04; Completion date: 2023-08-09
Enrollment: 21 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 2, open-label, single arm trial of pamrevlumab (FG-3019) to estimate pamrevlumab's safety and efficacy in non-ambulatory participants with DMD.

Detailed description:
The study will include a screening period, main study period, open-label extension (OLE) period, and follow-up period 4 weeks after the last dose. All participants who complete the main portion of the study for a minimum of 104 weeks (2 years) will be rolled over to an OLE for up to an additional 208 weeks (4 years).

Arms: arm 1: Participants will receive pamrevlumab 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 2 weeks for a minimum of 104 weeks. Participants who complete the main study, will continue to receive pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of up to 208 weeks in the OLE.
Interventions: intervention 1: Pamrevlumab
Intervention descriptions: intervention 1: Pamrevlumab, 10 milligrams (mg)/milliliter (mL), single dose vials

Protocol documents:
Prot_002.pdf: 
TITLE PAGE 
CLINICAL STUDY PROTOCOL 
STUDY TITLE: 
Trial of Pamrevlumab (FG-3019), a Monoclonal 
Antibody to Connective Tissue Growth Factor, in 
Non-Ambulatory Subjects with Duchenne Muscular 
Dystrophy 
PROTOCOL NUMBER: 
FGCL-3019-079 
PHASE: 
2 
SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
IND NUMBER: 
126630 
STUDY DRUG: 
Pamrevlumab (FG-3019) 
INDICATION: 
Duchenne Muscular Dystrophy 
FIBROGEN MEDICAL 
MONITOR: 
 
FibroGen, Inc. 
 
Telephone: 
 
Mobile: 
 
 
E-mail Address:  
ORIGINAL PROTOCOL: 
16 June 2015 
AMENDMENT 1.0: 
31 August 2015 
AMENDMENT 2.0: 
06 May 2016 
AMENDMENT 3.0: 
09 December 2016 
AMENDMENT 4.0: 
10 July 2017 
AMENDMENT 5.0: 
14 November 2017 
AMENDMENT 6.0: 
AMENDMENT 7.0: 
AMENDMENT 8.0 
14 November 2018 (Site Specific – Site 7903 and 
7913) 
27 September 2019 
18 November 2020 
CONFIDENTIALITY STATEMENT 
The information contained in this document is confidential and proprietary to FibroGen, Inc. No part of this 
document or any of the information contained herein may be transmitted, disclosed, shared, reproduced, 
published or utilized by any persons without prior written authorization by FibroGen, Inc.
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INVESTIGATOR SIGNATURE PAGE STUDY ACKNOWLEDGEMENT 
Trial of Pamrevlumab (FG-3019), a Monoclonal Antibody to Connective Tissue Growth Factor, 
in Non-Ambulatory Subjects with Duchenne Muscular Dystrophy 
 
FGCL-3019-079 
Original: 16 June 2015 
Amendment 1.0: 31 August 2015 
Amendment 2.0: 06 May 2016 
Amendment 3.0: 09 December 2016 
Amendment 4.0: 10 July 2017 
Amendment 5.0: 14 November 2017 
Amendment 6.0: 14 November 2018 (Site Specific – Site 7903 and 7913) 
Amendment 7.0: 27 September 2019 
Amendment 8.0: 18 November 2020 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices and the current Investigator’s Brochure (IB), and I agree that it 
contains all necessary details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all information provided 
by FibroGen, Inc. I will discuss this material with them to ensure that they are fully informed about the drugs and 
the study. 
I will conduct the trial in accordance with the guidelines of Good Clinical Practice (GCP) including the archiving of 
essential documents, the Declaration of Helsinki, any applicable local health authority, and Institutional Review 
Board (IRB) requirements. 
 
 
 
Investigator Name (Printed) 
 
Institution 
 
 
 
Signature 
 
Date 
Please return a copy of this signature page to FibroGen’s designee. Please retain the original for your study 
files.
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CONFIRMATION OF PROTOCOL APPROVAL 
Original Protocol Date: 16 June 2015 
Amendment 1.0: 31 August 2015 
Amendment 2.0: 06 May 2016 
Amendment 3.0: 09 December 2016 
Amendment 4.0: 10 July 2017 
Amendment 5.0: 14 November 2017 
Amendment 6.0: 14 November 2018 (Site Specific – Site 7903 and 7913) 
Amendment 7.0: 27 September 2019 
Amendment 8.0: 18 November 2020 
 
This protocol is approved by FibroGen. 
 
 
 
 
 
 
 
 
, FibroGen, Inc. 
 
Date 
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AMENDMENT 8.0: KEY CHANGES (ALL SITES) 
The protocol has been edited for clarity, consistency, and quality of content (typos, grammatical 
errors, etc.) A redline version documenting all changes from the previous version of this 
document is available upon request. 
Key Change 
Rationale 
Sections Affected 
Safety follow-up extended to 60 days (+3 
days) after the last infusion 
To align with safety follow-up of 5 
times half-life of Pamrevlumab of 
12.2 days 
Section 7.1.5, 8.3.1, and 
Appendix 6: OLE 
Removed Upper Arm Muscle MRI and 
Respiratory Muscles and Diaphragm MRI 
and associated endpoints from OLE. 
Changes in Fibrosis/MRI endpoints 
are not a direct measure of patient 
function and are of uncertain 
clinical meaningfulness as a 
biomarker of disease progression. 
Therefore, Fibrosis/MRI endpoints 
will only be in the main study, and 
only Cardiac MRI will be 
conducted in the OLE.  
Respiratory Muscles and 
Diaphragm MRI is not a direct 
measure of pulmonary function, 
which is measured on this study 
through spirometry to reflect the 
impact of pamrevlumab on 
pulmonary function.    
Section 7.1.2, and Appendix 
6: OLE 
IP administration window time updated 
from 24 to 48 hours 
To align with updated stability 
information for Pamrevlumab 
Section 6.1.4 
ECGs removed 
To align with standard of care 
Appendix 6: OLE 
Provide further clarity on the overall 
duration of the Open Label Extension. 
For better readability and clarity on 
the length of the OLE 
Appendix 6: OLE 
Modified open label extension assessments 
including labs, PFTs and physical exams 
To align further with standard of 
care for improved implementation 
Appendix 6: OLE 
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Provide allowance for administration of 
approved DMD therapies during the OLE 
treatment period >3hours after pamrevlumab 
administration 
To allow administration of 
approved DMD therapies during 
the OLE treatment period 
Synopsis, Appendix 6: OLE 
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1. 
PROTOCOL SYNOPSIS 
 
Study Title: 
Trial of Pamrevlumab (FG-3019), a Monoclonal Antibody to 
Connective Tissue Growth Factor, in Non-Ambulatory 
Subjects with Duchenne Muscular Dystrophy 
Protocol Number: 
FGCL-3019-079, Amendment 8.0 
Investigational Product: 
Pamrevlumab (FG-3019) (Recombinant fully human IgG1 
kappa monoclonal antibody to connective tissue growth factor) 
Study Phase: 
Phase 2 
Target Population: 
Non-ambulatory subjects with Duchenne muscular dystrophy 
(DMD) 
Number of Subjects Planned: 
Approximately 22 subjects will be enrolled; interim analysis 
may increase sample size to approximately 32 
Study Centers Planned: 
Approximately 10 centers 
OBJECTIVES 
Primary Objective 
To estimate pamrevlumab’s efficacy in non-ambulatory subjects with DMD 
Secondary Objectives 
1. To evaluate safety and tolerability of pamrevlumab administered intravenously every 
2 weeks 
2. To assess pharmacokinetics of pamrevlumab in the targeted pediatric population 
3. To evaluate pharmacodynamic markers of pamrevlumab’s effects in DMD 
ENDPOINTS/ASSESSMENTS 
Efficacy 
Primary Endpoint 
• Annual change from baseline to Week 104 in percent predicted forced vital 
capacity (FVC) during treatment with pamrevlumab. 
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Secondary Endpoints 
• Change from baseline to 104 weeks in forced expiratory volume (FEV1), maximum 
inspiratory pressure (MIP), maximum expiratory pressure (MEP), peak expiratory 
flow (PEF), peak cough flow 
• Change in LVEF from baseline to Week 104 
• Change from baseline to Week 104 in Performance of Upper Limb (PUL) Score 
• Change from baseline to Week 104 in grip strength, pinch strength, and Brooke 
scale for upper extremity 
• Change from baseline to Week 104 in cardiac fibrosis score assessed by 
magnetic resonance imaging (MRI) 
• Change from baseline to Week 104 in upper arm (bicep) muscle fat and 
fibrosis assessed by MRI 
Exploratory, Pharmacokinetics, Pharmacodynamics 
• Pharmacokinetic (PK) profile of pamrevlumab (including Cmin, Cmax, 
AUCtau, and t1/2) [In the first 12 subjects to have PK/PD samples though Day 
14] 
o In the overall population 
o In subjects 12 to 16 years of age, inclusive 
o In subjects older than 16 years 
o Comparison of PK profiles across age groups 
• Plasma and urine connective tissue growth factor (CTGF) 
• Creatine kinase (CK) 
• Circulating biomarkers 
• Exploratory analyses on primary and secondary efficacy endpoints at week 156 
will be conducted at the end of the study. 
Safety 
Adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests and 
discontinuation of treatment for treatment-related AEs serve as the safety assessments 
for this trial. 
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STUDY DESIGN 
This study is an open-label, single arm study which will initially enroll approximately 
22 subjects and includes an open label extension (OLE). Each subject will receive 
pamrevlumab (35 mg/kg, every 2 weeks) for a minimum of 104 weeks and will 
transition onto the OLE within 2-3 infusions from the approval of the amendment for 
up to an additional 208 weeks (refer to appendix 6). An interim analysis will be 
conducted after at least 10 to 12 subjects have completed 52 weeks of treatment. As a 
result, sample size may be readjusted to a total of approximately 32 subjects.  
All subjects will be closely monitored for safety (including trends of pulmonary 
function tests: FVC, mean inspiratory flow, and peak expiratory flow). 
STUDY PROCEDURES 
Details regarding study procedures are provided as follows: 
Appendix 1: Screening Period through Week 26 
Appendix 2: Week 28 through Week 58 
Appendix 3 : Week 60 through Week 104 
Appendix 4: Week 106 through Week 210/EOS 
Appendix 5: Specialty Lab Schedule 
Appendix 6: Open Label Extension 
MAIN SELECTION CRITERIA 
Inclusion Criteria 
Subjects must meet all of the following criteria in order to be eligible for the study: 
1. At least 12 years of age 
2. Written consent/assent by patient and/or legal guardian as per regional and/or 
IRB requirements 
3. Non-ambulatory 
4. Brooke Score for Arms and Shoulders ≤5 
5. Diagnosis of DMD by medical history and confirmed Duchenne mutation 
in available genetic testing using a validated genetic test 
6. Able to perform spirometry 
7. Able to undergo cardiac and extremity (upper arm) MRI 
8. Percent predicted FVC between 40 and 90, inclusive 
9. At least one historical FVC % predicted value within 18 months of baseline 
10. Left ventricular ejection fraction ≥45% as determined by cardiac MRI 
at screening or within 3 months prior to Day 0 
11. Subjects currently receiving heart failure cardiac medications (e.g., 
angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and 
beta-blockers) must achieve a stable regimen for at least 3 months prior to 
screening 
12. On a stable dose of corticosteroids for a minimum of 6 months prior to 
screening with no substantial change in dosage for a minimum of 3 months 
(except for adjustments for changes in body weight) prior to screening and no 
foreseen change in corticosteroid use during the course of study participation. 
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13. Received pneumococcal vaccine and is receiving annual influenza vaccinations 
14. Adequate renal function: cystatin C ≤1.4 mg/L 
15. Adequate hematological function: 
a. Platelets >100,000/mcL 
b. Hemoglobin >12 g/dL 
c. Absolute neutrophil count >1500 /μL 
16. 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 
17. If sexually active, will use medically accepted contraceptives during 
participation in the study and for 3 months after last dose of study drug. 
Exclusion Criteria 
Subjects must not meet any of the following criteria in order to be eligible: 
1. Requires ≥16 hours continuous ventilation 
2. Prior or ongoing medical condition that in the investigator's opinion, could 
adversely affect the safety of the subject, makes it unlikely that the course of 156 
weeks of treatment and follow-up would be completed, or could impair the 
assessment of study results 
3. Anticipated spine surgery within 156 weeks 
4. Severe uncontrolled heart disease including any of the following: 
a. Need for intravenous diuretics or inotropic support within 3 months prior 
to screening 
b. Hospitalization for a heart failure exacerbation or arrhythmia in last 3 months 
5. Arrhythmia requiring anti-arrhythmic therapy 
6. Hospitalization due to respiratory failure in the last 6 weeks 
7. Poorly controlled asthma or underlying lung disease such as 
bronchopulmonary dysplasia 
8. Known or suspected active hepatitis B or C or history of HIV 
9. BMI ≥40 kg/m2 or weight >117 kg 
10. Exposure to another investigational drug or another approved product for DMD 
(e.g. eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of 
the product whichever is longer) prior to first screening visit with the exception of 
deflazacort. Use of deflazacort if regarded by the principal investigator as standard 
of care is allowed. 
TREATMENTS 
Pamrevlumab Dose, and Mode of Administration 
Each subject will receive pamrevlumab (35 mg/kg, every 2 weeks) for a minimum of 
104 weeks and will transition onto the OLE within 2-3 infusions of the approval of the 
amendment for up to an additional 208 weeks. The dose of pamrevlumab (35 mg/kg) 
for the first infusion should be based on body weight obtained during screening. Dose 
will be adjusted based on body weight taken approximately every 3 months thereafter. 
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Concomitant Medications/Therapies:  
Subjects will receive full supportive care as required by their clinical condition. 
Management of corticosteroid dose is up to the discretion of the physician. All 
subjects should be monitored for osteoporosis in accordance with the respective 
institutional standard of care for DMD patients receiving glucocorticoid therapy. 
Investigational agents, and those that receive marketing authorization, or approved 
product for DMD (e.g. eteplirsen) during this trial are prohibited during the main 
study and allowed during the Open Label Extension at the discretion of the 
investigator. Use of deflazacort if regarded by the principal investigator as standard of 
care is allowed. Subjects with female partners of childbearing potential are required to 
use two forms of contraception during the conduct of the study and for 3 months after 
the last dose of study drug. 
 
 
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STATISTICAL METHODS 
A total of 22 subjects is planned to achieve 80% power to test the null hypothesis of 
change in percent predicted FVC of -5% against the alternative  hypothesis, assuming a 
mean change of -2% and standard deviation of 5%, based on a 2-sided one sample t-test 
at 0.05 significance level.    
The primary efficacy endpoint will be met if the annual change in percent predicted 
FVC is above -5% after 104 weeks of treatment with pamrevlumab (lower bound of 
the 2-sided 95% confidence interval is above -5%). 
An interim analysis will be conducted after at least 10 to 12 subjects have completed 1 
year of treatment. As a result, sample size may be readjusted to a total of approximately 
32 subjects. 
The primary efficacy endpoint is the annual change from baseline to Week 104 in 
percent predicted FVC during treatment with pamrevlumab.  The mean annual change 
in percent predicted FVC and the corresponding 2-sided 95% confidence interval will 
be presented.  
Final analysis of the primary and secondary endpoints will be described in the 
statistical analysis plan. Details of the interim analysis will be described in an interim 
analysis plan.  
Pamrevlumab concentrations and derived PK parameters will be tabulated and 
summarized using descriptive statistics. Descriptive statistics (number of subjects, 
mean, geometric mean, standard deviation, minimum, maximum, and coefficient of 
variation) will be presented for the PK parameters. Attainment of steady-state will be 
investigated. 
Safety analyses will include summary of adverse events (including treatment 
emergent AEs, treatment emergent serious AEs, deaths, and infusion-associated 
AEs), prior and concomitant medication use, measurements of laboratory tests, vital 
signs, and electrocardiograms (ECGs), and physical exams. 
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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR SIGNATURE PAGE STUDY ACKNOWLEDGEMENT ...............................2 
INVESTIGATOR STATEMENT ...................................................................................................2 
CONFIRMATION OF PROTOCOL APPROVAL.........................................................................3 
AMENDMENT 8.0: KEY CHANGES (ALL SITES) ....................................................................4 
1. 
PROTOCOL SYNOPSIS .............................................................................................6 
2. 
INTRODUCTION ......................................................................................................16 
2.1. 
Description of Pamrevlumab ......................................................................................16 
2.2. 
Duchenne Muscular Dystrophy ..................................................................................16 
2.2.1. 
Relevance of Connective Tissue Growth Factor (CTGF) in DMD ............................17 
2.3. 
Summary of Relevant Findings from Nonclinical and Clinical Trials .......................17 
2.3.1. 
Nonclinical Studies .....................................................................................................17 
2.3.2. 
Pharmacokinetics ........................................................................................................18 
2.3.3. 
Safety ..........................................................................................................................18 
2.3.4. 
Efficacy .......................................................................................................................18 
2.4. 
Risks and Benefits ......................................................................................................19 
2.5. 
Description of and Justification for the Route of Administration, Dosage, 
Dosage Regimen, and Treatment Periods ...................................................................20 
2.6. 
Good Clinical Practice and Regulatory Requirements ...............................................20 
2.7. 
Population to be Studied .............................................................................................20 
3. 
OBJECTIVES .............................................................................................................21 
3.1. 
Primary Objective .......................................................................................................21 
3.2. 
Secondary Objectives .................................................................................................21 
4. 
STUDY DESIGN .......................................................................................................22 
4.1. 
Endpoints and Assessments ........................................................................................22 
4.1.1. 
Primary Endpoint ........................................................................................................22 
4.1.2. 
Secondary Endpoints ..................................................................................................22 
4.1.3. 
Exploratory, Pharmacokinetic and Pharmacodynamic Outcome Measures ...............22 
4.1.4. 
Safety Assessments .....................................................................................................23 
4.2. 
Trial Overview ............................................................................................................23 
4.3. 
Study Treatment ..........................................................................................................23 
4.3.1. 
Dose and Schedule ......................................................................................................23 
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4.3.2. 
Rationale for Dose and Schedule ................................................................................23 
4.4. 
Concomitant Medications, Procedures and Nondrug Therapies ................................23 
4.4.1. 
Contraception ..............................................................................................................24 
4.5. 
Safety Plan ..................................................................................................................24 
4.6. 
Data Monitoring Committee .......................................................................................24 
5. 
STUDY ENROLLMENT AND WITHDRAWAL ....................................................25 
5.1. 
Inclusion Criteria ........................................................................................................25 
5.2. 
Exclusion Criteria .......................................................................................................26 
5.3. 
Subject Withdrawal ....................................................................................................26 
5.4. 
Replacement of Subjects .............................................................................................26 
5.5. 
Study Termination ......................................................................................................27 
6. 
STUDY DRUG/TREATMENT SUPPLY .................................................................28 
6.1. 
FibroGen Investigational Product ...............................................................................28 
6.1.1. 
Formulation .................................................................................................................28 
6.1.2. 
Study Drug Packaging and Labeling ..........................................................................28 
6.1.3. 
Storage ........................................................................................................................28 
6.1.4. 
Preparation of Dose for Administration .....................................................................28 
6.1.5. 
Administration ............................................................................................................29 
7. 
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS .............................30 
7.1. 
Study Procedures by Visit ..........................................................................................30 
7.1.1. 
Screening Period (no earlier than Day -28) ................................................................30 
7.1.2. 
Dosing Period .............................................................................................................31 
7.1.3. 
End of Treatment ........................................................................................................31 
7.1.4. 
Early Withdrawal from Treatment and Safety Follow-up Period ..............................31 
7.1.5. 
Safety Follow-Up Period ............................................................................................31 
7.1.6. 
Missed Visits ..............................................................................................................31 
7.1.7. 
Unscheduled Visits .....................................................................................................32 
7.2. 
Assessments (Main Study) .........................................................................................32 
7.2.1. 
Pulmonary Function Tests ..........................................................................................32 
7.2.2. 
Muscle Strength and Functional Measurements .........................................................32 
7.2.3. 
Cardiac MRI ...............................................................................................................32 
7.2.4. 
Muscle MRI ................................................................................................................32 
7.2.5. 
Quality of Life Questionnaire .....................................................................................32 
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7.2.6. 
Vital Signs and Physical Examinations ......................................................................32 
7.2.7. 
Laboratory Assessments .............................................................................................33 
8. 
ASSESSMENT OF SAFETY .....................................................................................35 
8.1. 
Background .................................................................................................................35 
8.2. 
Definitions ..................................................................................................................35 
8.2.1. 
Definition of an Adverse Event (AE) .........................................................................35 
8.2.2. 
Definition of a Serious Adverse Event (SAE) ............................................................35 
8.2.3. 
Definition of an Infusion Reaction .............................................................................36 
8.2.4. 
Acute Infusion Reaction .............................................................................................36 
8.2.5. 
Special Situations ........................................................................................................36 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events ........................37 
8.3.1. 
Adverse Event Reporting Period ................................................................................37 
8.3.2. 
Adverse Event Eliciting/Reporting .............................................................................37 
8.3.3. 
Assessing Adverse Event Severity .............................................................................38 
8.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug ......................................38 
8.3.5. 
Reporting Serious Adverse Events on the SAE Report Form ....................................39 
8.3.6. 
Pregnancies: Reporting and Follow-up of Subjects ....................................................40 
8.3.7. 
Abnormal Laboratory Findings ..................................................................................40 
9. 
STATISTICAL CONSIDERATIONS .......................................................................41 
9.1. 
Sample Size Determination ........................................................................................41 
9.2. 
Analysis Populations ..................................................................................................41 
9.2.1. 
Safety Population ........................................................................................................41 
9.2.2. 
Full Analysis Set Population ......................................................................................41 
9.3. 
Statistical Analysis ......................................................................................................41 
9.3.1. 
General Considerations ...............................................................................................41 
9.3.2. 
Subject Enrollment and Disposition ...........................................................................42 
9.3.3. 
Demographics and Baseline Characteristics ...............................................................42 
9.4. 
Efficacy Analyses .......................................................................................................42 
9.4.1. 
Primary Endpoint ........................................................................................................42 
9.4.2. 
Analyses of Other PFT Parameters .............................................................................42 
9.4.3. 
Analysis of PUL Parameters, Pinch and Grip Strength, Brooke Scale ......................42 
9.4.4. 
Analysis of LVEF, Cardiac Fibrosis, and Muscle Fat and Fibrosis ...........................42 
9.4.5. 
Analysis of PODCI Quality Outcome Data ................................................................42 
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9.4.6. 
Pharmacokinetic Analyses ..........................................................................................42 
9.4.7. 
Safety Analyses ..........................................................................................................43 
9.5. 
Administrative Analyses .............................................................................................43 
10.
DIRECT ACCESS TO SOURCE DOCUMENTS .....................................................44
11.
QUALITY CONTROL AND QUALITY ASSURANCE .........................................45
11.1. 
Data Quality Assurance ..............................................................................................45 
11.2. 
Audit and Inspection ...................................................................................................45 
12.
ETHICS ......................................................................................................................46
12.1. 
Ethical Considerations ................................................................................................46 
12.2. 
Communication with the Institutional Review Board or Independent Ethics 
Committee ...................................................................................................................46 
12.3. 
Informed Consent Form ..............................................................................................46 
12.4. 
Subject Confidentiality ...............................................................................................47 
13.
DATA HANDLING AND RECORD KEEPING ......................................................48
13.1. 
Source Documents ......................................................................................................48 
13.2. 
Data Collection, Handling, and Verification ..............................................................48 
14.
PUBLICATION POLICY ..........................................................................................49
15.
REFERENCES ...........................................................................................................50
16.
APPENDICES ............................................................................................................52
APPENDIX 1. SCHEDULE OF ASSESSMENTS: SCREENING PERIOD 
        THROUGH WEEK 26 .......................................................................................53 
APPENDIX 2. SCHEDULE OF ASSESSMENTS: WEEK 28 THROUGH WEEK 58 ............54 
APPENDIX 3. SCHEDULE OF ASSESSMENTS: WEEK 60 THROUGH WEEK 104 ..........55 
APPENDIX 4. SCHEDULE OF ASSESSMENTS: WEEK 106 THROUGH 
        WEEK 210/EOS .................................................................................................56 
APPENDIX 5. SPECIALTY LAB SCHEDULE ........................................................................58 
APPENDIX 6. OPEN LABEL EXTENSION (OLE) .................................................................59 
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2. 
INTRODUCTION 
2.1. 
Description of Pamrevlumab 
Pamrevlumab is a recombinant fully human immunoglobulin G1 (IgG) kappa monoclonal 
antibody to connective tissue growth factor (CTGF) and is being developed for treatment of 
diseases in which tissue fibrosis has a major pathogenic role. These diseases include liver 
fibrosis due to hepatitis, 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 (Emery, 1991). 
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). 
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). 
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). 
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2.2.1. 
Relevance of Connective Tissue Growth Factor (CTGF) in DMD 
Connective tissue growth factor (CTGF) is a nonstructural regulatory protein present in the 
extracellular matrix that has an important role in fibrosis. Skeletal muscle from DMD patients, 
dystrophic dogs, and mdx mice all show elevated levels of CTGF (Sun, 2008). 
CTGF can reproduce or amplify the effects of TGFβ on fibrosis by inducing collagen type 1, 
α5 integrin, and fibronectin much more potently than TGFβ 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 to the medium, and respond to the growth factor by 
increasing the extracellular matrix constituents, partially inhibiting myoblasts differentiation and 
inducing myoblasts dedifferentiation (Vial, 2008). 
In DMD, the role of CTGF might extend well beyond replacement fibrosis secondary to loss of 
muscle fibers, since its overexpression in skeletal muscle could by itself induce a dystrophic 
phenotype (Morales, 2013). 
A major feature of the hearts of DMD patients is cardiac fibrosis. Cardiac fibrosis is associated 
with increased CTGF expression in the mdx mouse heart. CTGF may be a key mediator of early 
and persistent fibrosis in dystrophic cardiomyopathy (Au, 2011). 
CTGF is critically involved in several chronic fibro-degenerative diseases. Pamrevlumab 
treatment has been shown to positively the affect the course of several of these diseases in Phase 
1 and Phase 2 clinical studies. 
2.3. 
Summary of Relevant Findings from Nonclinical and Clinical Trials 
Please refer to the most recent version of pamrevlumab Investigator’s Brochure. 
2.3.1. 
Nonclinical Studies 
In DMD, the genetic loss of the cytoskeletal protein dystrophin results in muscle damage that, 
leads to progressive replacement of muscle with fibrotic and fat tissue. This progressive muscle 
damage can be recapitulated in the DMD mouse model (mdx), and accelerated by muscle usage 
(Pessina, 2014). 
As was observed with genetic depletion of CTGF, pharmacologic inhibition of active CTGF in 
mdx mice by treatment with pamrevlumab resulted in reduced fibrosis and skeletal muscle 
damage, as well as improved preservation of skeletal muscle strength in isolated muscles. The 
pamrevlumab treated mdx mice were also subjected to a test of exercise endurance, in which 
they showed better performance than mdx mice injected with control IgG (Morales, 2013). 
Pamrevlumab treatment of mdx mice was associated with decreased skeletal muscle damage and 
fibrosis, decreased collagen III and fibronectin expression, decreased plasma creatine kinase 
(CK) (Morales, 2013), and increased isometric force of skeletal muscle (Morales, 2011). 
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2.3.2. 
Pharmacokinetics 
Key findings are summarized below from Phase 1 and 2 studies investigating the 
pharmacokinetics (PK) of pamrevlumab in subjects with diabetic kidney disease, idiopathic 
pulmonary fibrosis, liver fibrosis and pancreatic cancer: 
• Pamrevlumab was administered over the dose range of 3 to 45 mg/kg every 2 weeks, 
every 3 weeks, and 17.5 to 22.5 mg/kg weekly. 
• Pamrevlumab exposure (e.g., mean/median Cmax and Cmin, area under the curve 
[AUC]) generally increased with increasing dose. 
• For single dose studies, for doses > 10 mg/kg the t1/2 did not appear to increase with 
increasing pamrevlumab doses, based on available data with estimated mean 
t1/2 values of approximately 1 week. 
• For multiple dose studies, the mean t1/2 following multiple doses (3 to 10 mg/kg) 
also increased from 102 to 135 hours. 
− The estimated t1/2 values for doses > 10 mg/kg did not appear to increase 
markedly with dose, based on available data (limited time points). 
2.3.3. 
Safety 
Key findings are summarized below from the Phase 1 and 2 studies involving more than 
400 adults with diabetic kidney disease, idiopathic pulmonary fibrosis, and liver fibrosis due to 
hepatitis B or pancreatic cancer: 
• Overall, pamrevlumab was well tolerated across the range of doses noted above, and 
there were no dose-limiting toxicities. 
• Treatment-emergent adverse events (TEAEs) were generally mild or moderate in 
severity and transient in duration. 
• Infusion-related reactions have been mild-to-moderate and are considered an 
identified risk of pamrevlumab administration. 
• TEAEs were considered typical of the subjects’ underlying medical condition(s) and, 
in the placebo-controlled studies, were equally distributed between placebo and 
pamrevlumab treatment groups. 
• No apparent pattern to TEAEs that occurred within 24 hours after infusions was 
observed. 
• No apparent pattern for treatment-emergent serious adverse events (TESAEs) was 
observed during clinical testing. 
2.3.4. 
Efficacy 
Key efficacy findings are summarized below from the Phase 1 and 2 studies of CTGF inhibition 
by pamrevlumab in indications other than DMD. 
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2.3.4.1. 
Pancreatic Cancer 
Biweekly doses of up to and including 45 mg/kg and weekly doses of 17.5 and 
22.5 mg/kg were administered to subjects with previously untreated locally advanced or 
metastatic pancreatic adenocarcinoma. Increased exposure to pamrevlumab was associated with 
increased survival. There appears to be a relationship between survival and trough blood levels 
of pamrevlumab (Cmin). Notably Cmin >150 mcg/mL after the first dose of pamrevlumab 
(Day 15) was associated with significantly increased progression free survival and overall 
survival. 
A maximal effect in survival benefit was achieved at dose levels of 25 to 45 mg/kg/2 weeks. 
2.3.4.2. 
Idiopathic Pulmonary Fibrosis (IPF) 
In subjects with IPF who completed 45 weeks of dosing with 15 or 30 mg/kg pamrevlumab, 
approximately 40% of subjects had stable or improved lung fibrosis by quantitative high 
resolution CT imaging compared to baseline values with approximately 30% having improved 
pulmonary fibrosis. 
Overall, subjects with stable or improved lung fibrosis also had stable or improved FVC 
(% predicted). 
2.4. 
Risks and Benefits 
Pamrevlumab has been generally well tolerated with most adverse events being typical of those 
expected for subjects with the underlying disease conditions. 
Infusion-related reactions have been observed in some subjects treated with pamrevlumab. 
Across studies in other indications, infusion-related reactions have been mild-to-moderate did 
not result in discontinuation of treatment with pamrevlumab, and did not result in the use of 
prophylaxis for subsequent infusions. 
The favorable experience with pamrevlumab to date does not exclude the possibility of more 
severe infusion reactions occurring in future subjects. 
This is the first clinical study of pamrevlumab in DMD. There are currently no confirmed 
benefits to subjects with DMD treated with pamrevlumab. However, a potential benefit of 
treatment with pamrevlumab is indicated in preclinical models of DMD and previous clinical 
studies of pamrevlumab in other indications where CTGF is also associated with disease 
progression. 
Dose regimens equal to or exceeding 35 mg/kg have been implemented in other indications in 
adult subjects. The objective of these studies was to inhibit bioactive CTGF, which is associated 
with disease progression in a number of indications. Please refer to the Investigator’s Brochure 
for a comprehensive summary of efficacy, safety, and exposure data. 
The current study will explore the clinical relevance of CTGF inhibition, as indicated in 
preclinical models, in DMD patients. 
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2.5. 
Description of and Justification for the Route of Administration, 
Dosage, Dosage Regimen, and Treatment Periods 
Pamrevlumab is administered as an IV infusion at a dose of 35 mg/kg every two weeks (Main 
study Day 0 to a minimum of Week 104, and OLE Day 0 up to Week 208/EOT). The dose, 
frequency and route of administration correspond with dose regimens that were well tolerated 
and possibly associated with efficacy in clinical studies in adults with IPF and pancreatic cancer. 
In both of these indications pamrevlumab was administered at doses that included the targeted 
dose regimen for the current study (35 mg/kg bodyweight) and greater (45 mg/kg bodyweight). 
These doses were not associated with dose limiting toxicity. 
The overall objective of all of these studies, including the current study, is to provide a dose 
associated with clinically relevant CTGF blockade to impede progression of serious disease 
states. Body weight-related dosing and utilization of a dose no greater than the maximal dose 
used in adults are expected to ensure that systemic exposure in the targeted pediatric population 
will not exceed the systemic exposure achieved in adults. 
PK assessments will be done during the course of the study and facilitate ongoing monitoring of 
exposure to pamrevlumab during the course of the study. 
The planned treatment duration is no longer than total treatment periods achieved in previous 
studies with pamrevlumab. 
The duration of treatment of the current study is also similar to the duration of other studies in 
DMD and is expected to provide sufficient basis to evaluate potential benefit in the targeted 
pediatric population with DMD. 
2.6. 
Good Clinical Practice and Regulatory Requirements 
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. 
Detailed information regarding study conduct is found in Sections 10, 11, 12, and 13. 
2.7. 
Population to be Studied 
Non-ambulatory adolescents and adults with DMD will be enrolled in this trial. A detailed 
inclusion/exclusion list is provided in Section 5. 
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3. 
OBJECTIVES 
3.1. 
Primary Objective 
The primary objective of this trial is to estimate pamrevlumab’s efficacy in non- ambulatory 
subjects with DMD. 
3.2. 
Secondary Objectives 
The following are the secondary objectives of this trial: 
1. To evaluate safety and tolerability of pamrevlumab administered intravenously every 
2 weeks 
2. To assess pharmacokinetics of pamrevlumab in the targeted pediatric population 
3. To evaluate pharmacodynamic markers of pamrevlumab’s effects in DMD 
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4. 
STUDY DESIGN 
4.1. 
Endpoints and Assessments 
4.1.1. 
Primary Endpoint 
The primary endpoint is the annual change from baseline to Week 104 in percent predicted 
forced vital capacity (FVC) during treatment with pamrevlumab. 
4.1.2. 
Secondary Endpoints 
The following are the secondary endpoints: 
• Change from baseline to Week 104 in forced expiratory volume (FEV1), maximum 
inspiratory pressure (MIP), maximum expiratory pressure (MEP), peak expiratory 
flow (PEF), peak cough flow 
• Change in LVEF from baseline to Week 104 
• Change from baseline to Week 104 in Performance of Upper Limb (PUL) Score 
• Change from baseline to Week 104 in grip strength, pinch strength, and Brooke scale 
for upper extremity 
• Change from baseline to Week 104 in cardiac fibrosis score assessed by MRI 
• Change from baseline to Week 104 in upper arm (bicep) muscle fat and fibrosis 
assessed by MRI 
4.1.3. 
Exploratory, Pharmacokinetic and Pharmacodynamic Outcome Measures 
Exploratory outcome measures for this trial are: 
• Pharmacokinetic (PK) profile of pamrevlumab (including Cmin, Cmax, AUCtau, and 
t1/2) [In the first 12 subjects to have PK/PD samples though Day 14] 
− In the overall population 
− In subjects 12 to 16 years of age, inclusive 
− In subjects older than 16 years 
− Comparison of PK profiles across age groups 
• Plasma and urine CTGF 
• Creatine kinase (CK) 
• Circulating biomarkers 
• Exploratory analyses on primary and secondary efficacy endpoints at week 156 will 
be conducted at the end of the study. 
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4.1.4. 
Safety Assessments 
Adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests and 
discontinuation of treatment for treatment-related AEs serve as the safety assessments for this 
trial. 
4.2. 
Trial Overview 
This study will be an open-label, single arm study that will initially enroll approximately 
22 subjects and includes an open label extension (OLE). Each subject will receive pamrevlumab 
(35 mg/kg, every 2 weeks) for a minimum of 104 weeks and will transition onto the OLE within 
2-3 infusions from the approval of the amendment An interim analysis will be conducted after at 
least 10 to 12 subjects have completed 1 year of treatment. As a result, sample size may be 
readjusted to a total of approximately 32 subjects. 
All subjects will be closely monitored for safety (including trends of pulmonary function tests: 
FVC, mean inspiratory flow, and peak expiratory flow) on a continuous basis. 
Upon completion of treatment or premature discontinuation from the trial, subjects will be asked 
to return to the investigative site to complete final safety and efficacy assessments. 
4.3. 
Study Treatment 
4.3.1. 
Dose and Schedule 
Each subject will receive pamrevlumab (35 mg/kg) intravenously every 2 weeks (q2w). See 
Section 6 for detailed information on study drug formulation, storage, and administration. 
4.3.2. 
Rationale for Dose and Schedule 
The pamrevlumab dose is based on results of a study in adult subjects with pancreatic cancer. In 
that study (Section 2.3.4.1), minimum pamrevlumab blood levels (Cmin) 
≥150 mcg/mL were associated with increased median survival and 1 year survival compared to 
subjects with Cmin <150 mcg/mL. Given the apparent threshold effect for increased benefit 
when minimal pamrevlumab exposure is ≥150 mcg/mL and based on PK analysis using these 
data, the planned dose of 35 mg/kg administered every 2 weeks is projected to achieve this 
minimum exposure in the targeted DMD study population. 
4.4. 
Concomitant Medications, Procedures and Nondrug Therapies 
Subjects will receive full supportive care as required by their clinical condition. Management of 
corticosteroid dose is up to the discretion of the physician. All subjects should be monitored for 
osteoporosis in accordance with the respective institutional standard of care for DMD patients 
receiving glucocorticoid therapy. 
Investigational agents, and those that receive marketing authorization during this trial, or 
approved product for DMD (e.g. eteplirsen) are prohibited. Use of deflazacort if regarded by the 
principal investigator as standard of care is allowed. 
Concomitant medications (any prescription and/or over-the-counter [OTC] preparation) and 
procedures or nondrug therapies (e.g., physical therapy or acupuncture) used by a subject while 
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participating in this clinical trial must be recorded from the Screening Visit through the End-of-
Study Visit. 
Questions regarding potential impact of concomitant medications on evaluability of subjects 
should be addressed to the attention of the FibroGen Medical Monitor. 
4.4.1. 
Contraception 
Subjects with female partners of childbearing potential are required to use two forms of 
contraception during the conduct of the study and for 3 months after the last dose of study drug. 
Pregnancy, spontaneous or therapeutic abortion, or events related to pregnancy of a partner must 
be reported (Section 8.3.6). 
4.5. 
Safety Plan 
An ongoing safety review is facilitated by the unblinded nature of the study. FibroGen will 
review safety data and will communicate the results of these reviews to investigators by email or 
teleconference on a regular basis. In addition, FibroGen will review safety experience with 
investigators during teleconferences that will be held at least quarterly and include the 
conclusions of the Data Monitoring Committee’s (DMC) latest data review. 
FibroGen will notify investigators immediately if a new safety risk is identified. 
4.6. 
Data Monitoring Committee 
A DMC will be utilized and will be composed of external experts. Composition and 
responsibilities of the DMC are defined in a separate DMC charter. 
DMC responsibilities include review of safety data, and may include available pharmacokinetic 
data, and pulmonary function tests. 
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5. 
STUDY ENROLLMENT AND WITHDRAWAL 
5.1. 
Inclusion Criteria 
Subjects must meet all of the following criteria in order to be eligible for the study: 
1. At least 12 years of age 
2. Written consent/assent by patient and/or legal guardian as per regional and/or IRB 
requirements 
3. Non-ambulatory 
4. Brooke Score for Arms and Shoulders ≤5 
5. Diagnosis of DMD by medical history and confirmed Duchenne mutation in available 
genetic testing using a validated genetic test 
6. Able to perform spirometry 
7. Able to undergo cardiac and extremity (upper arm) MRI 
8. Percent predicted FVC between 40 and 90, inclusive 
9. At least one historical FVC % predicted value within 18 months of baseline 
10. Left ventricular ejection fraction ≥45% as determined by cardiac MRI at screening or 
within 3 months prior to Day 0 
11. Subjects currently receiving heart failure cardiac medications (e.g. angiotensin converting 
enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a 
stable regimen for at least 3 months prior to screening 
12. On a stable dose of corticosteroids for a minimum of 6 months prior to screening with no 
substantial change in dosage for a minimum of 3 months (except for adjustments for 
changes in body weight) prior to screening and no foreseen change in corticosteroid use 
during the course of study participation 
13. Received pneumococcal vaccine and is receiving annual influenza vaccinations 
14. Adequate renal function: cystatin C ≤1.4 mg/L 
15. Adequate hematological function: 
a. Platelets >100,000/mcL 
b. Hemoglobin >12 g/dL 
c. Absolute neutrophil count >1500 /μL 
16. Adequate hepatic function: 
a. No history or evidence of liver disease 
b. gamma glutamyl transferase (GGT) ≤3 x upper limit of normal (ULN) 
c. Total bilirubin ≤1.5xULN 
17. If sexually active, will use medically accepted contraceptives during participation in the 
study and for 3 months after the last dose of study drug 
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5.2. 
Exclusion Criteria 
Subjects must not meet any of the following criteria in order to be eligible: 
1. Requires ≥16 hours continuous ventilation 
2. Prior or ongoing medical condition that in the investigator's opinion, could adversely 
affect the safety of the subject, makes it unlikely that the course of 156 weeks of 
treatment and follow-up would be completed, or could impair the assessment of study 
results 
3. Anticipated spine surgery within 156 weeks 
4. Severe uncontrolled heart disease including any of the following: 
a. Need for intravenous diuretics or inotropic support within 3 months prior to screening 
b. Hospitalization for a heart failure exacerbation or arrhythmia in last 3 months 
5. Arrhythmia requiring anti-arrhythmic therapy 
6. Hospitalization due to respiratory failure in the last 6 weeks 
7. Poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia 
8. Known or suspected active hepatitis B or C or history of HIV 
9. BMI ≥40 kg/m2 or weight >117 kg 
10. Exposure to another investigational drug or another approved product for DMD (e.g. 
eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of the product 
whichever is longer) prior to first screening visit with the exception of deflazacort. Use of 
deflazacort if regarded by the principal investigator as standard of care is allowed. 
5.3. 
Subject Withdrawal 
Subjects may withdraw from the study at any time. 
The investigator may remove a subject from study treatment for the following reasons: 
• Adverse events, which in the opinion of the Principal Investigator and/or FibroGen 
preclude further study drug dosing 
• Nonadherence to protocol-defined procedures, in particular missing of 3 or more 
sequential study drug infusions 
• Not available for safety assessments 
Subjects who discontinue the study early should be strongly encouraged to complete the 
evaluations described in Section 7.1.3. 
5.4. 
Replacement of Subjects 
Subjects may be replaced in this study if a subject’s participation is not terminated due to safety 
or tolerability issues and is replaced prior to completion of targeted recruitment into the study. 
Replacement decisions will be made between the sponsor and investigator on a case-by-case 
basis. 
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5.5. 
Study Termination 
This trial can be terminated by the sponsor at any time for any reason. 
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6. 
STUDY DRUG/TREATMENT SUPPLY 
6.1. 
FibroGen Investigational Product 
Pamrevlumab is a fully human IgG1 kappa monoclonal antibody that binds to CTGF. 
6.1.1. 
Formulation 
Pamrevlumab is supplied in single-use glass vials containing 10 mL or 50 mL of a 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.  If different vial sizes or 
new formulations are introduced during the course of the study, updates to formulation, storage, 
etc. will be provided through an amendment to the Pharmacy Manual and investigative site staff 
training.  
6.1.2. 
Study Drug Packaging and Labeling 
Labels will be prepared and will comply with Good Manufacturing Practice and USA regulatory 
guidelines. 
6.1.3. 
Storage 
Vials of pamrevlumab 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. 
6.1.4. 
Preparation of Dose for Administration 
The dose of pamrevlumab (35 mg/kg) for the first infusion should be based on body weight 
obtained during screening. Dose will be adjusted based on body weight taken every 3 months 
thereafter. Pamrevlumab may be administered undiluted or, for convenience of infusion, may be 
diluted with 0.9% Sodium Chloride Injection according to the Dose Preparation Instructions in 
the Study Reference Investigational Product (IP) Manual. 
Pamrevlumab will be administered as soon as possible after release from the site’s pharmacy and 
within 48 hours of preparation and within 6 hours if left at room temperature after preparation. 
Pamrevlumab 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). 
 
 
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6.1.5. 
Administration 
 
Study Drug 
Dose 
Route 
Infusion Rate 
Schedule 
Pamrevlumab 
35 mg/kg 
IV 
Not to exceed 150 cc/hour 
Every 
2 weeks 
DO NOT ADMINISTER PAMREVLUMAB AS AN IV PUSH OR BOLUS INJECTION, 
OR CONCURRENTLY IN THE IV LINE WITH OTHER AGENTS. 
Subjects who weigh more than 117 kg will receive the maximum allowed dose of 4.1 g. For this 
study, the overall rate of infusion for the prepared study drug should not exceed 150 cc/hour. 
Adjustments may be made to further slow the rate of infusion (infusing less than 150 cc/hour) in 
accordance with the investigator’s clinical judgement. Subjects should be carefully monitored for 
reaction during the first infusion with a physician available as needed. Subjects will remain at the 
study site for 1 hour after the end of the infusion for clinical observation. The IV access should 
remain in place and be maintained per site procedures until the end of this post treatment 
observation period. If a subject has an infusion reaction, the infusion rate may be slowed or 
temporarily stopped, depending on the severity of symptoms. If a subject experiences an infusion 
reaction and continues pamrevlumab dosing, a physician must be immediately available during 
subsequent infusions and observation periods until the subject does not have any infusion 
reaction for three sequential infusions. 
Premedication, such as antihistamines, corticosteroids or nonsteroidal anti-inflammatory drugs 
(NSAIDs) are not normally administered before infusions of pamrevlumab. 
Premedication may be used for subjects who experience infusion reactions at the discretion of 
the investigator after discussion with the Medical Monitor. 
Pamrevlumab will be administered in a hospital or ambulatory setting with adequate facilities for 
managing medical emergencies for at least three infusions to confirm the subject does not have 
an infusion reaction. The study site must have trained staff and medications for the treatment of 
acute reactions, including anaphylaxis, immediately available. There is no specific treatment for 
a pamrevlumab overdose or infusion reaction. Signs and symptoms should be managed with 
appropriate standard of care treatment. 
FibroGen may consider the use of properly trained home health care staff to administer the 
pamrevlumab infusions in the future and corresponding study assessments during the conduct of 
the study, consistent with institutional regulations and policies. 
 
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7. 
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS 
7.1. 
Study Procedures by Visit 
All study procedures and assessments for the main study will be performed in accordance with 
the Schedule of Assessments presented in Section 16 and in Appendix 6 for the OLE. 
For all potential subjects, screening procedures required to determine subject eligibility will be 
performed within 28 days prior to Day 0 (first infusion of pamrevlumab). 
Potential subjects may be re-screened if initial screening procedures lie outside the 28-day 
screening period prior to planned study entry. 
Subject’s eligibility for this study will be reviewed and approved by Sponsor’s medical monitor 
prior to subject enrollment. 
The following assessments are relevant to the assessment of efficacy: pulmonary function tests 
(FVC, mean inspiratory flow (MIF), peak expiratory flow), Brooke Upper Extremity Rating 
Scale, Performance of the Upper Limb, pinch strength, grip strength, cardiac MRI, and muscle 
MRI. Refer to the Study Reference Manual for details. 
Approved windows for performing study assessments are defined in the following sections. 
7.1.1. 
Screening Period (no earlier than Day -28) 
Assessments to be conducted during the screening period are presented in Appendix 1. 
Screening assessments may be completed over several visits during the screening period. It is 
recommended that the less invasive screening assessments be performed first upon completion of 
the signed Informed Consent and/or Assent Form [ICF] (demographics, medical history, blood 
draws, electrocardiogram [ECG], vital signs (includes body weight and height), physical exam, 
pulmonary function tests (PFTs), and then followed by the more rigorous screening assessments 
(i.e., muscle function tests, cardiac MRI). 
A cardiac MRI performed within 3 months prior to Day 0 (start of dosing) is acceptable to 
confirm eligibility based on the LVEF study entry criterion and as baseline cardiac MRI. If an 
historic MRI is not available, a cardiac MRI must be performed during the Screening Period. 
An upper arm muscle MRI is not required to determine subject eligibility at screening, but may 
be conducted within the screening period (4 weeks prior to Day 0) or anytime up to Week 4 
dosing visit (4 weeks after Day 0). The results of this assessment are acceptable as baseline 
assessment. 
Muscle and pulmonary function tests (PFTs) will be performed during the screening period. 
Muscle function and PFTs will be repeated on Day 0 (start of dosing) or at any time up to and 
including the Week 2 visit. The results from both time points will be used to establish baseline 
values. 
If the subject cannot perform adequately due to illness (e.g. sinusitis, etc.) then the PFTs should 
be delayed until the subject can reliably perform the assessment within the 28-day screening 
window. 
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In addition, an exploratory blood sample will be drawn for analysis of circulating biomarkers of 
fibrosis and specific muscle miRNAs (dystromirs) prior to first pamrevlumab infusion. 
7.1.2. 
Dosing Period 
The dosing period begins on the first day of dosing with study treatment (Day 0) and continues 
for a minimum of 104 weeks. Subjects will transition onto the OLE within 2-3 infusions from the 
approval of the amendment. Subjects will receive study drug every 2 weeks. 
The visit window for all dosing visits is ±2 days. Visits should be scheduled based on the 
previous visit, not the baseline visit. 
Assessments and procedures to be performed during the dosing period are presented in 
Section 16. 
Muscle or pulmonary function tests 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. 
MRIs may be performed within ±2 weeks of the specified visit. 
Blood samples will be drawn for pharmacokinetic analysis according to the schedule in 
Appendix 5. Blood draws to be collected on non-dosing days may be collected within ±1 day as 
outlined in Appendix 5. 
7.1.3. 
End of Treatment  
Assessments and procedures to be conducted after the last dose of study drug on the main study 
are presented in Appendix 4 .  
All subjects who complete 104 weeks of treatment will be offered continued participation via the 
OLE.  If the subject consents to ongoing treatment, the EOT MRIs must be performed within 
7 days of EOT. 
7.1.4. 
Early Withdrawal from Treatment and Safety Follow-up Period 
Subjects who prematurely discontinue the main study should be strongly encouraged to complete 
the final efficacy evaluations scheduled for Week 208/EOT as applicable, and the safety follow-
up evaluations scheduled for the Week 210/EOS visit (4 weeks following the last dose). 
Subjects who withdraw prior to week 104 will not be eligible to participate in the OLE. 
7.1.5. 
Safety Follow-Up Period 
For all subjects, the final safety assessments should be completed 4 weeks (±7 days) after the last 
dose of pamrevlumab, and subjects will receive a final safety follow-up phone call 60 days (+ 3 
days) after the last dose. 
7.1.6. 
Missed Visits 
Every attempt must be made to complete all study visits as outlined in the Schedules of 
Assessments. Missed infusions will not be replaced. If a subject misses a scheduled efficacy 
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assessment, the assessment should be performed as soon after the missed visit as feasible and 
within the windows specified above. 
7.1.7. 
Unscheduled Visits 
Unscheduled Visit assessments may be required at the discretion of the investigator. 
7.2. 
Assessments (Main Study) 
Please refer to the Schedules of Assessments for the main study for the scope and timing of 
assessments. Please refer to the Laboratory Manual for details regarding laboratory sample 
collection and processing; and the Study Reference Manual for details regarding the conduct of 
functional tests and MRIs. 
7.2.1. 
Pulmonary Function Tests 
The following pulmonary function tests (PFTs) will be performed to assess changes in lung 
function: forced vital capacity (FVC), maximal inspiratory pressure (MIP), maximum expiratory 
pressure (MEP) and peak expiratory flow rate (PEF; PEFR), forced expiratory volume in 
1 second (FEV1), and peak cough flow (Mayer, 2015, Miller, 2005). 
7.2.2. 
Muscle Strength and Functional Measurements 
The following assessments will be performed to assess changes in upper extremity strength and 
function: Brooke Upper Extremity Rating Scale (Brooke Scale), Performance of the Upper Limb 
(PUL), Grip Test, and Pinch Strength Test. 
7.2.3. 
Cardiac MRI 
Cardiac MRIs will be performed as per Section 16 to assess changes in left ventricular ejection 
fraction (LVEF) and presence of late gadolinium enhancement (LGE), a marker for myocardial 
fibrosis. 
7.2.4. 
Muscle MRI 
An upper arm muscle MRI at screening, will be conducted within the screening period (4 weeks 
prior to Day 0) or anytime up to Week 4 dosing visit (4 weeks after Day 0). The results of this 
assessment are acceptable as baseline assessment. 
Upper arm (bicep) muscle MRIs will be performed as per Section 16.  
7.2.5. 
Quality of Life Questionnaire 
Pediatrics Outcomes Data Collection Instrument (PODCI) Quality Outcome Questionnaire will 
be performed to assess if treatment with pamrevlumab improves quality of life. 
7.2.6. 
Vital Signs and Physical Examinations 
A physical examination will be performed at screening and baseline (Day 0), approximately 
every 12 weeks and at Week 208/EOT. Complete physical exams will be performed at screening, 
Week 48, Week 104, Week 156, and Week 208/ EOT. Other examinations may be disease-
specific or problem-oriented examinations. 
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Vital signs (pulse, respiration, sitting blood pressure, and temperature) will be collected at 
screening and at all visits. During infusion visits, vital signs will be collected prior to start of 
each infusion, within 15 minutes of the end of each infusion, and within 15 minutes of the 
completion of the post-infusion observation period. 
7.2.7. 
Laboratory Assessments 
All laboratory tests of blood and/or urine specimens will be performed at a central laboratory or 
FibroGen, as appropriate. A Central Laboratory Manual with instructions on specimen 
collection, processing, storing, and shipping to the central laboratory will be provided to all 
participating sites. 
Local clinical laboratories will be used to assess and facilitate the management of adverse events 
and to provide usual standard of care (including blood draws required prior to MRIs). Local 
clinical laboratory data will not be collected in the study database except for hematocrit values 
provided with imaging data. 
7.2.7.1. 
Safety Assessments 
Blood samples will be drawn for the following analyses: complete blood count, gamma glutamyl 
transferase (GGT), total bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), 
alanine transaminase (ALT), and albumin, creatine kinase (CK), and cystatin C. 
Safety labs will be drawn at the site’s local lab prior to MRIs to ensure there is no 
contraindication to MRI. Hematocrit should be included in the local lab draw as these results are 
required to assess fibrosis and will be provided to the central imaging vendor along with the MRI 
scans. Details are included in the Imaging Manual. 
7.2.7.2. 
Pharmacokinetics 
Plasma concentrations of pamrevlumab will be determined on Day 0 pre-dose and within 1 hour 
post infusion, then on Days 2, 4, 7, 10, and 14. The Day 14 sample should be on the same day of, 
but prior to the start of the next infusion of study drug. 
Day 2, 4, 7, and 10 PK assessments represent target days following the first dose; however, 
actual sample collection time of up to ±1 day of the target time is acceptable as long as the actual 
time of dosing and actual time of each sample collection are recorded accurately. 
At Weeks 26 and 52, trough pamrevlumab levels (Cmin) will be determined prior to study drug 
infusion. 
PK samples will also be drawn within 60 minutes of infusion completion at Week 52. 
7.2.7.3. 
Plasma and Urine CTGF 
Plasma and urine samples will be analyzed for CTGF concentrations from samples taken as 
described in Appendix 5. 
7.2.7.4. 
HAHA 
Blood samples will be drawn for analysis of human anti-human antibody (HAHA) according to 
the schedule in Appendix 5. 
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7.2.7.5. 
Biomarkers 
Blood samples will be drawn for analysis of biomarkers according to the schedule in 
Appendix 5. The exact biomarkers will be based on current scientific knowledge regarding 
CTGF, pamrevlumab and DMD at the time the tests are performed. No genetic testing will be 
performed. 
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8. 
ASSESSMENT OF SAFETY 
8.1. 
Background 
Adverse event reports from investigators are the critical building blocks to the development of 
the safety profile of the Study Drug. Subjects will be asked non-leading questions in general 
terms to determine the occurrence of AEs, according to the schedule outlined in Section 16. In 
addition, all AEs reported spontaneously during the course of the study will be recorded. The 
investigator must immediately (within 24 hours of awareness) report to the sponsor or designated 
safety management vendor all SAEs, regardless of whether the investigator believes they are 
related to the Study Drug. 
8.2. 
Definitions 
8.2.1. 
Definition of an Adverse Event (AE) 
For the purpose of this study, an AE is any untoward medical occurrence that occurred in the 
protocol-specified AE reporting period, and which does not necessarily have a causal 
relationship with the study drug. An AE includes medical conditions, signs, and symptoms not 
previously observed in the subject that emerge during the 
protocol-specified AE reporting period, including signs or symptoms associated with an 
underlying condition that were not present prior to the AE reporting period (Section 8.3.1). 
8.2.2. 
Definition of a Serious Adverse Event (SAE) 
A serious adverse event is any adverse event or suspected adverse reaction that results in any of 
the following outcomes: 
• Death, 
• A life-threatening AEs (i.e., if in the view of the investigator or sponsor, the subject 
was at immediate risk of death at the time of the event). Life-threatening does not 
refer to an event which hypothetically might have caused death if it were more 
severe, 
• Inpatient hospitalization or prolongation of existing hospitalization, 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, 
• A congenital anomaly or birth defect, or 
• Is considered a medically important event not meeting the above criteria, but which 
may jeopardize a subject or may require medical or surgical intervention to prevent 
one of the other criteria listed in this definition. Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or 
at home, and blood dyscrasias or convulsions that do not result in inpatient 
hospitalization. 
Please note that death is an outcome, not an event; the cause of death would be the adverse event. 
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Surgical procedures, per se, are not SAEs. The condition requiring the surgical procedure, 
however, may be an SAE. 
Scheduled hospitalization or prolongation of a hospitalization due to standard of care 
assessments and procedures do not warrant reporting as adverse events unless resulting 
observations are deemed by the Investigator to meet the definition of an adverse event. 
8.2.3. 
Definition of an Infusion Reaction 
Infusion reactions are immunologic reactions to an infused protein, and are different from events 
resulting from the process of infusing the protein (e.g., infusion site bruise) and are different 
from adverse events due to the infused protein’s intended or unintended pharmacologic effects. 
8.2.4. 
Acute Infusion Reaction 
An acute infusion reaction is one that meets both of the following criteria: 
1. Occurs during or within 1 hour after infusion; and 
2. Clinical manifestations consistent with: 
a. IgE-mediated and non-IgE mediated hypersensitivity reactions, including but not 
limited to urticaria, skin rashes, angioedema, laryngeal edema, bronchospasm, 
gastrointestinal symptoms and hypotension; or 
b. Cytokine release syndrome, including but not limited to fever, respiratory symptoms 
without the presence of wheezing, tremors, chills, flushing, pruritus, changes in blood 
pressure, dyspnea, chest discomfort, back pain, nausea, vomiting, diarrhea, and skin 
rashes. 
8.2.4.1. 
Delayed Infusion Reaction 
A delayed infusion reaction is one that meets both of the following criteria: 
1. Occurs ≥1 hour after the infusion 
2. Clinical manifestations as described above. 
8.2.4.2. 
Reporting Possible and Confirmed Infusion Reactions 
Both acute and delayed infusion reactions will be captured as AEs and also be reported to the 
medical monitor within 24 hours. See Study Reference Manual for additional details. 
8.2.5. 
Special Situations 
Certain safety events, called ‘Special Situations’ that occur in association with the study drug(s) 
include, but are not limited to: 
• Overdose of the medicinal product 
• Suspected abuse/misuse of the medicinal product 
• Inadvertent or accidental exposure to the medicinal product 
• Medication error involving the medicinal product (with or without subject/patient 
exposure to the Sponsor medicinal product, e.g., name confusion) 
• Drug-drug interaction 
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Special Situations will be reported to the sponsor or designated vendor within 24 hours on a 
Medication Error report form. See Study Reference Manual for details. 
8.3. 
Procedures for Eliciting, Recording, and Reporting Adverse Events 
8.3.1. 
Adverse Event Reporting Period 
The study period during which all AEs and SAEs must be reported begins after informed consent 
is obtained and ends 4 weeks after the last dose of study drug, except for pregnancy reporting 
(Section 8.3.6). In addition, all AEs reported spontaneously by the subject to site personnel, 
outside the study period, may be recorded. The investigator should notify FibroGen of any death 
or other SAEs occurring after a subject has discontinued or terminated study participation that 
may reasonably be related to this study (Section 8.3.5). 
Adverse events will be followed until resolved, stable, or until the subject’s last study visit and 
final safety follow-up phone call 60 days (+ 3 days) after the last dose. 
or subject is lost to follow-up. 
8.3.2. 
Adverse Event Eliciting/Reporting 
During the AE reporting period, study site personnel will query each subject at each visit to 
actively solicit any AE occurring since the previous visit. All AEs will be collected in response 
to a general question about the subject’s well-being and any possible changes from the BL or 
previous visit, but shall not be specifically solicited. There will be no directed questioning for 
any specific AE. This does not preclude the site from collecting and recording any AEs reported 
by the subject to site personnel at any other time. 
Whenever is possible, diagnoses should be recorded when signs and symptoms are due to a 
common etiology, as determined by qualified medical study staff. 
New indications for medications started during the AE reporting period (i.e., after informed 
consent is obtained until 4 weeks after the last dose of study drug) will be recorded as AEs; 
recurrence or worsening of medical history problems requiring new or changes in concomitant 
medication, will also be recorded as AEs. Clinically significant laboratory results, physical 
examination findings, and ECGs will be recorded as AEs if they are deemed by the Investigator 
to meet the specified criteria. 
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 
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• Determination of “seriousness” 
8.3.3. 
Assessing Adverse Event Severity 
AEs, including abnormal clinical laboratory values, should be graded using the National Cancer 
Institute (NCI) Common Terminology Criteria for AE (CTCAE) v 4.0 guidelines. For terms not 
specified as part of NCI CTCAE, the following guidelines should be used to determine grade: 
All AEs will be assessed for severity using the following criteria: 
• Grade 1, Mild: Asymptomatic or mild symptoms which the subject finds easily 
tolerated. The event is of little concern to the subject and/or of little-or-no clinical 
significance; intervention not indicated. 
• Grade 2, Moderate: The subject has enough discomfort to cause interference with or 
change in some of their age-appropriate instrumental activities of daily living (e.g., 
preparing meals, shopping for groceries or clothes, using the telephone, managing 
money); local or noninvasive intervention indicated. 
• Grade 3, Severe: The subject is incapacitated and unable to work or participate in 
many or all usual activities. The event is of definite concern to the subject and/or 
poses substantial risk to the subject’s health or well-being; ; likely to require medical 
intervention and/or close follow-up, including but not limited to hospitalization or 
prolongation of hospitalization. 
• Grade 4, Life-threatening:  The subject was at immediate risk of death from the 
event as it occurred. 
• Grade 5, Death: Fatal AE. 
8.3.4. 
Assessing the Adverse Event’s Relationship to Study Drug 
Most of the information about the safety of a drug prior to marketing comes from clinical trials; 
therefore, AE reports from investigators are critically important. The assessment of whether an 
AE is causally related to the study drug(s) using an evidence-based approach is critical in order 
to appropriately describe the safety profile study drug(s). Default reporting of individual events 
as possibly related is uninformative and does not meaningfully contribute to the development of 
the study drug’s safety profile. 
The investigator must provide an evidence-based assessment of the relationship of the AE to 
study drug in accordance with the guidance below. Absence of an alternative cause would not 
normally be considered sufficient evidence to assess an event as related to study drug. 
• Related: 
− Any event for which there is sufficient evidence to suggest that the study drug 
may have caused the event. For example, an unanticipated medical condition 
occurs which resolves with study drug interruption and re- occurs with re-
administration of study drug; another example is a typical drug-related medical 
condition such as a rash that occurred shortly after first dose of study drug. 
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• Not Related: 
− The event represents a pre-existing underlying disease that has not worsened on 
study 
− The event has the same characteristics of a known side-effect associated with a 
co-medication 
− The event is an anticipated medical condition of anticipated severity for the study 
population 
− The most plausible explanation for the event is a factor that is independent of 
exposure to study drug 
8.3.5. 
Reporting Serious Adverse Events on the SAE Report Form 
An SAE must be reported to the Sponsor and/or its designated safety management vendor within 
24 hours of becoming aware of the SAE. 
To report an SAE, the investigator must complete an SAE Report Form and fax or email the 
completed form to the Sponsor or its designated safety management vendor. 
Full details of the SAE should also be recorded on the medical records and in the CRF. The 
following minimum information is required: 
• Subject number, sex and age 
• The date of report 
• A description of the SAE (event, seriousness of the event) 
• Causal relationship to the study drug 
Follow-up information for the event should be sent promptly. 
For each SAE observed, the investigator should obtain all of the information available about the 
event, including (but not limited to): hospital discharge diagnoses, hospital discharge note, death 
certificate, appropriate laboratory findings (including autopsies and biopsy results), and clinical 
examinations (including radiological examinations and clinical consultations). 
The contact information for SAE reporting is as follows: 
U.S. Toll-Free Fax Number: 1-215-616-3096-Email: FibroGen_SAEs@iconplc.com 
8.3.5.1. 
Reporting Serious Adverse Events to the Institutional Review Board / 
Independent Ethics Committee 
The investigator is responsible for notifying his/her Institutional Review Board (IRB) or Ethics 
Committee (EC) of SAEs in accordance with local regulations. 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. 
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8.3.5.2. 
Deaths 
The investigator will report the fatal or life-threatening event immediately to the Sponsor’s 
medical monitor. The investigator must provide a causal assessment of the relationship of the 
event to the study drug according to the guidance in Section 8.3.5. 
If the death occurred within the AE collection and reporting period (signed ICF to 
4 weeks after last dose) and meets the reporting criteria, the investigator must submit the SAE 
Report Form in the same manner as described above in Section 8.3.5. Additionally, the site must 
complete the appropriate CRF page. 
8.3.6. 
Pregnancies: Reporting and Follow-up of Subjects 
The outcome of all pregnancies should be followed up and documented as described. Consent 
must be obtained from male subject’s partner to collect information related to the pregnancy and 
outcome (and will be handled on a case-by-case basis with IRB/IEC approval). A Pregnancy 
Report Form must be completed and submitted to Sponsor or designated safety management 
vendor within 24 hours of the investigator becoming aware of the pregnancy. The investigator 
must follow-up to completion of the pregnancy to ascertain its outcome (e.g., spontaneous 
miscarriage, elective termination, ectopic pregnancy, normal birth or congenital abnormality) 
and whether any AEs occur during the pregnancy or birth. The outcome of the pregnancy must 
be reported by the investigator on a Pregnancy Outcome Report Form, which should be sent to 
the Sponsor and/or its designated safety vendor within 24 hours of the investigator becoming 
aware of the outcome. 
8.3.7. 
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 laboratory results throughout the study in a 
timely manner, and determine whether any abnormal laboratory values, if any, are clinically 
significant (CS) or not clinically significant (NCS), and whether there are associated signs and 
symptoms. Clinically significant laboratory abnormalities will be reported as AEs. 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.). 
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. 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Sample Size Determination 
This study tests the hypothesis of whether pamrevlumab can attenuate the annual decline from 
baseline to Week 104 in FVC in non-ambulatory DMD patients. A total of 22 subjects is planned 
to achieve 80% power to test the null hypothesis of change in percent predicted FVC of -5% 
against the alternative hypothesis, assuming a mean change of -2% and standard deviation of 5% 
based on 2-sided one sample t-test at 0.05 significance level.  The hypotheses are: 
H0: change in percent predicted FVC less than or equal to -5% 
Ha: change in percent predicted FVC greater than -5%. 
The primary efficacy endpoint will be met if the annual change in percent predicted FVC is 
greater than -5% at the end of the study (lower bound of 2-sided 95% confidence interval is 
greater than -5%). 
9.2. 
Analysis Populations 
9.2.1. 
Safety Population 
The Safety Population will consist of all subjects who have received any dose of pamrevlumab. 
This population is also defined as the intent-to-treat (ITT) population. 
9.2.2. 
Full Analysis Set Population 
The Full Analysis Set Population (FAS) will consist of all subjects in the Safety Population who 
have at least one evaluable post-baseline FVC assessment. 
9.3. 
Statistical Analysis 
9.3.1. 
General Considerations 
Descriptive summaries will be provided for all study parameters including baseline 
characteristics, safety, efficacy, pharmacokinetic and pharmacodynamic parameters. Continuous 
variables will be reported using number of subjects, mean, standard deviation or standard error, 
median, minimum, and maximum. In general, standard deviation is provided to describe the 
distribution of a parameter, such as baseline, safety, and PK/PD parameters; standard error is 
provided for statistical analyses of efficacy endpoints. Geometric mean will be included for 
PK/PD variables. Categorical variables will be reported by the frequency and percentage of 
subjects within each outcome category. Two-sided 95% confidence intervals will be presented 
for key efficacy parameters and two-sided 90% confidence intervals for PK/PD parameters. All 
statistical tests will be performed at α=0.05 level of significance, using two-sided tests, unless 
otherwise stated. Assessments as well as derived parameters will be presented in data listings for 
all subjects in the ITT/Safety Population. 
Statistical consideration for the OLE are included in Section 16, Appendix 6. Detailed 
description of the analyses and summaries of efficacy and safety will be presented in the SAP. 
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9.3.2. 
Subject Enrollment and Disposition 
The number of subjects in each study population as well as subject completion status and reasons 
for early discontinuation will be summarized. 
9.3.3. 
Demographics and Baseline Characteristics 
Subject demographics, baseline characteristics, baseline disease characteristics, and baseline 
efficacy measures will be summarized. Baseline disease characteristics include general medical 
history, disease specific characteristics, and prior treatments. Baseline efficacy measures include 
PFT parameters, hand and arm functions, cardiac and muscle MRI parameters, and quality of life 
parameters. 
9.4. 
Efficacy Analyses 
Efficacy analyses will be based on the FAS population. Rules of handling missing data will be 
described in the Statistical Analysis Plan (SAP). Analyses based on observed data will be 
performed for sensitivity evaluation. 
9.4.1. 
Primary Endpoint 
The primary endpoint is the annual change from baseline to Week 104 in percent predicted FVC 
during treatment with pamrevlumab. The mean annual change in percent predicted FVC and the 
corresponding 2-sided 95% confidence interval will be presented. The primary efficacy endpoint 
will be met if the lower bound of 2-sided 95% confidence interval is greater than -5%. 
9.4.2. 
Analyses of Other PFT Parameters 
Changes from baseline to Week 104 in other PFT parameters will be estimated similarly; details 
of missing data handling will be described in the statistical analysis plan (SAP). 
9.4.3. 
Analysis of PUL Parameters, Pinch and Grip Strength, Brooke Scale 
Change from baseline to Week 104 in hand/arm function and strength will be analyzed.  In order 
to evaluate overall effect, composite scores may be explored.   Two-sided 95% confidence 
intervals will be presented. 
9.4.4. 
Analysis of LVEF, Cardiac Fibrosis, and Muscle Fat and Fibrosis 
Changes from baseline in LVEF, cardiac fibrosis, and muscle fat and fibrosis will be summarized 
descriptively based on available data at Week 104. 
9.4.5. 
Analysis of PODCI Quality Outcome Data 
Changes from baseline in modified PODCI scores of subjects will be summarized descriptively 
based on available data at each assessment time point. 
9.4.6. 
Pharmacokinetic Analyses 
Pamrevlumab concentrations and derived PK parameters (including Cmin, Cmax, AUCtau, and 
t1/2) will be summarized using descriptive statistics. Pharmacokinetic analysis will be performed 
using commercial software such as WinNonlin. 
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Descriptive statistics (number of subjects, mean, geometric mean, standard deviation, minimum, 
maximum, and coefficient of variation) will be presented for the PK parameters (1) in the overall 
population, (2) in subjects 12 to 16 years of age, and (3) in subjects older than 16 years. 
Comparison of PK parameters between the age groups will be performed. Trough values, 
measured at several time points during the course of the study, will be compared to determine 
steady state and accumulation. 
9.4.7. 
Safety Analyses 
Safety analyses will include summary of adverse events, prior and concomitant medication use, 
measurements of laboratory tests, vital signs, and electrocardiograms (ECGs). In general, safety 
data will only be summarized descriptively and no inferential statistical procedures will be 
applied. 
For data summarization, adverse events will be classified into standard terminology using a 
coding thesaurus (MedDRA), and reported by system organ class and preferred term. 
Treatment-emergent adverse events will be tabulated to examine their frequency, severity, organ 
systems affected and relationship to study treatment. Deaths, SAEs, and AEs leading to study or 
treatment discontinuation, and infusion reactions will be listed or tabulated separately. 
Clinically significant changes from baseline in vital signs, laboratory tests, and ECG will be 
identified. Shift tables will summarize changes in selected laboratory measures. 
All safety analyses will be performed based on the Safety Population.  
9.5. 
Administrative Analyses 
In this open-label exploratory study, safety will be monitored on an ongoing basis.   
The DMC will review all safety data, which may include available pharmacokinetic data, and 
pulmonary function tests. 
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10. 
DIRECT ACCESS TO SOURCE DOCUMENTS 
Following site prequalification and/or initiation of the study site, periodic monitoring visits and 
site closeout visits will be made by FibroGen or its designee. The investigator must provide 
direct access to, and allocate sufficient space and time for, the monitor to inspect subject source 
records, CRFs, queries, collection of local laboratory normal ranges (if applicable), 
investigational product accountability records, and regulatory documents in accordance with 
GCP and the International Conference on Harmonisation (ICH) E6 guideline. 
The purpose of trial monitoring is to verify the following: 
• The rights and well-being of human subjects are protected. 
• The reported data are accurate, complete, and verifiable from source documents 
• All data are collected, tracked, and submitted by the site to FibroGen or designee, 
including unscheduled and missed assessments 
• The reported data are reconciled across all data sources (e.g., laboratory, safety, IVRS 
[or IWRS], 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). 
The investigator must also permit the U.S. FDA or other applicable regulatory authorities to 
inspect facilities and records pertaining to this study if so requested. If the investigator is notified 
of an inspection pertaining to this study by the U.S. FDA or other applicable regulatory 
authorities, the investigator must notify FibroGen immediately. 
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11. 
QUALITY CONTROL AND QUALITY ASSURANCE 
11.1. 
Data Quality Assurance 
The following steps will be taken to ensure that the study is conducted by the study site in 
compliance with the study protocol, GCP, and other applicable regulatory requirements: 
• Investigator meeting and/or investigator site initiation 
• Routine study site monitoring 
• Documented study and system training 
• CRF and query review against source documents 
11.2. 
Audit and Inspection 
Authorized representatives of the sponsor, a regulatory authority, an independent ethics 
committee (IEC) or an institutional review board (IRB) may visit the investigator site to perform 
audits or inspections, including source data verification. The Investigator will allow the sponsor 
auditor, regulatory authority or ethics committee representative to inspect the drug storage area, 
study drug stocks, drug accountability records, subject charts 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, GCP guidelines of 
the International Conference on Harmonization, and any applicable regulatory requirements. 
The investigator should contact the sponsor immediately if contacted by a regulatory agency 
about an inspection. 
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12. 
ETHICS 
12.1. 
Ethical Considerations 
The study will be conducted in accordance with U.S. Food and Drug Administration (FDA) 
regulations, 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. 
12.2. 
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 more 
frequently in accordance with the regulatory requirements and policies and procedures 
established by the IRB/IEC. Copies of the investigator’s annual report and other required report 
to the IRB/IEC and copies of the IRB/IEC continuance of approval must be furnished to 
FibroGen. A copy of the signed form FDA 1572 must also accompany the above approval letter 
provided to FibroGen. 
Investigators are also responsible for promptly informing the IRB/IEC of any protocol changes 
or amendments, changes to the Investigator’s Brochure, and other safety-related communications 
from FibroGen. Written documentation of IRB approval must be received before the amendment 
is implemented. 
Investigators must also enter the names of the staff that are involved in the study on the 
Delegation of the Authority form and sign the form (including their responsibilities). This form 
must be updated when responsibilities of the staff change. 
12.3. 
Informed Consent Form 
No study procedure may be implemented prior to obtaining a signed, written Informed Consent 
(ICF) and/or Assent Form from the subject or written Informed Consent Form signed by the 
subject’s legally authorized representative, as applicable. IRB review and approval are required 
for the ICF. The final IRB/IEC approved ICF must be provided to FibroGen for regulatory 
purposes. 
If there are any changes to the Sample 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. 
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 
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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. 
12.4. 
Subject Confidentiality 
Release of research results should preserve the privacy of medical information and must be 
carried out in accordance with Department of Health and Human Services Standards for Privacy 
of Individually Identifiable Health information, 45 CFR Parts 160 and 164, and HIPAA. 
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. 
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13. 
DATA HANDLING AND RECORD KEEPING 
13.1. 
Source Documents 
Source documents are original documents, data, and records that are relevant to the clinical 
study. The investigator 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 CRFs/eCRFs and resolved queries. 
13.2. 
Data Collection, Handling, and Verification 
All required data will either be entered onto CRFs/eCRFs by authorized site personnel or will be 
provided as a data transfer from authorized service providers (such as laboratory results from a 
central laboratory). Data will be entered or uploaded into a validated, clinical database compliant 
with 21 CFR Part 11 regulations. The database will be a secured, password-protected system 
with a full audit trail. 
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 prior to study completion, ensuring that all data is verifiable with source 
documents. 
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14. 
PUBLICATION POLICY 
A detailed explanation of FibroGen’s publication policy is described in the Clinical Trial 
Agreement. 
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15. 
REFERENCES 
Au CG, Butler TL, Sherwood MC, Egan JR, North KN, Winlaw DS (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 
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 
Desguerre I, Mayer M, Leturcq F, Barbet JP, Gherardi RK, Christov C (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 
Kharraz Y, Guerra J, Pessina P, Serrano AL, Munoz-Canoves P (2014) Understanding the 
process of fibrosis in Duchenne muscular dystrophy. Biomed Res Int 2014:965631 
Mayer OH, Finkel RS, Rummey C, et al. (2015) Characterization of pulmonary function in 
Duchenne Muscular Dystrophy. Pediatr Pulmonol 50: (5):487-494 
McKim DA, Katz SL, Barrowman N, Ni A, LeBlanc C (2012) Lung volume recruitment slows 
pulmonary function decline in Duchenne muscular dystrophy. Archives of Physical Medicine 
and Rehabilitation 93: (7):1117-1122 
Miller MR, Hankinson J, Brusasco V, et al. (2005) Standardisation of spirometry. Eur Respir J 
26: (2):319-338 
Morales MG, Cabello-Verrugio C, Santander C, Cabrera D, Goldschmeding R, Brandan E 
(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 
Pessina P, Cabrera D, Morales MG, et al. (2014) Novel and optimized strategies for inducing 
fibrosis in vivo: Focus on Duchenne Muscular Dystrophy. Skelet Muscle 4:7 
Phillips MF, Quinlivan RC, Edwards RH, Calverley PM (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 
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 
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 
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 
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Tangsrud SE, Carlsen KC, Lund-Petersen I, Carlsen KH (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 
Vial C, Zuniga LM, Cabello-Verrugio C, Canon P, Fadic R, Brandan E (2008) Skeletal muscle 
cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which 
induces their dedifferentiation. Journal of Cellular Physiology 215: (2):410-421 
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16. 
APPENDICES 
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APPENDIX 1. SCHEDULE OF ASSESSMENTS: SCREENING PERIOD THROUGH WEEK 26 
Assessmenta 
Screening 
Period 
(4 Weeks) 
Treatment Period (Weeks) 
Day 
 0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
Informed Consent & Assent 
X 
Inclusion/ Exclusion 
X 
Demographics 
X 
Medical History 
X 
Clinical laboratory assessmentsb,i 
X 
X 
X 
X 
X 
Vital Signsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight/Heightd 
X 
X 
X 
Electrocardiogram 
X 
Physical Examinatione 
X 
X 
X 
X 
Muscle function testsf 
X 
X 
X 
X 
Pulmonary function testsg 
X 
X 
X 
X 
Cardiac MRIi 
Xi 
Muscle MRIi 
Xi 
Specialty labsh 
X 
X 
X 
Pamrevlumab infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events & Concomitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PODCI Quality Outcome Questionnaire 
X 
X 
Abbreviations: MRI, magnetic resonance imaging; PODCI, Pediatrics Outcomes Data Collection Instrument 
a. See Section 7 for details on approved windows, assessments and dosing. 
b. Safety labs: See Section 7.2.7.1. Central labs are required at visits noted in this table.   
c. Vital signs (pulse, respiration, sitting BP, temperature) to be collected at every visit, and pre-infusion, within 15 minutes of completion, and within 15 minutes of completing observation 
period. 
d. Weight and height (estimated from ulna length) to be measured at screening and every 3 months thereafter. 
e. Physical exam to include assessment of subject’s ventilation use. A complete exam is required at screening. Other exams may be disease specific or problem oriented. 
f. Muscle function tests (MFT): Brooke Scale, Performance of Upper Limb, Pinch Test, and Grip Test. MFTs will be performed during the screening period. MFTs will be repeated on Day 
0 
(start of dosing) or at any time up to and including the Week 2 visit. The results from both time points will be used to establish baseline values. 
g. Pulmonary function tests (PFTs): forced vital capacity, forced expiratory volume in 1 second, maximal inspiratory pressure, maximum expiratory pressure, peak expiratory flow rate, 
peak 
cough flow. PFTs will be performed during the screening period. PFTs will be repeated on Day 0 (start of dosing) or at any time up to and including the Week 2 visit. The results 
from 
both time points will be used to establish baseline values. 
h. See Appendix 5 for pharmacokinetic/human antihuman antibody/connective tissue growth factor and Exploratory Sample collection details. 
i. Baseline muscle MRI may be conducted during the screening period or up to Week 4 dosing visit. Local safety labs are required prior to the MRIs, and must include hematocrit.
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APPENDIX 2. SCHEDULE OF ASSESSMENTS: WEEK 28 THROUGH WEEK 58 
Assessmenta 
Treatment Period (Weeks) 
28 
30 
32 
34 
36 
38 
40 
42 
44 
46 
48 
50 
52 
54,56,
58  
Clinical laboratory assessmentsb,i 
X 
X 
 
Vital Signsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight/Heightd 
X 
X 
 
Electrocardiogram 
X 
Physical Examinatione 
X 
X 
 
Muscle function testsf 
X 
X 
 
Pulmonary function testsg 
X 
X 
 
Cardiac MRIi 
X 
 
Muscle MRIi 
X 
 
Specialty labsh 
X 
Pamrevlumab infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events & Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PODCI Quality Outcome 
Questionnaire 
X 
Abbreviations: MRI, magnetic resonance imaging; PODCI, Pediatrics Outcomes Data Collection Instrument 
a. See Section 7 for details on approved windows, assessments and dosing. 
b. Safety labs: See Section 7.2.7.1. Central labs are required at visits noted in this table.   
c. Vital signs (pulse, respiration, sitting blood pressure, and temperature) to be collected at every visit, and pre-infusion, within 15 minutes of infusion completion and within 15 minutes of 
completing the observation period. 
d. Weight and height (estimated from ulna length) to be measured at screening and approximately every 3 months thereafter. 
e. Physical exam to include assessment of subject’s ventilation use. A complete exam is required at Week 48. Other exams may be disease specific or problem oriented. 
f. Muscle function tests: Brooke Scale, Performance of Upper Limb, Pinch Strength Test, and Grip Test. 
g. Pulmonary Function Tests (PFTs): forced vital capacity, forced expiratory volume in 1 second, maximal inspiratory pressure, maximum expiratory pressure, peak expiratory flow 
rate, 
peak cough flow. 
h. See Appendix 5 for pharmacokinetic/human antihuman antibody/connective tissue growth factor and Exploratory Sample collection details. 
i. Local safety labs are required prior to the MRIs and must include hematocrit.
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APPENDIX 3. SCHEDULE OF ASSESSMENTS: WEEK 60 THROUGH WEEK 104 
Assessmenta 
Treatment Period (Weeks) 
60 
62,64, 
66,68,70 
72 
74,76, 
78,80,82 
84 
86,88,90
,92,94 
96 
98,100,102 
104 
Clinical laboratory assessmentsb,i 
X 
 
X 
 
X 
 
X 
 
 
Vital Signsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight/Heightd 
X 
 
X 
 
X 
 
X 
 
 
Electrocardiogram 
 
 
 
 
 
 
 
 
X 
Physical Examinatione 
X 
 
X 
 
X 
 
 
 
X 
Muscle function testsf 
X 
 
X 
 
X 
 
 
 
X 
Pulmonary function testsg 
X 
 
X 
 
X 
 
 
 
X 
Cardiac MRIi 
 
 
 
 
 
 
 
 
X 
Muscle MRIi 
 
 
 
 
 
 
 
 
X 
Specialty labsh 
 
 
 
 
 
 
 
 
X 
Pamrevlumab infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events & Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PODCI Quality 
Outcome Questionnaire 
 
 
 
 
 
 
 
 
X 
Abbreviations: MRI, magnetic resonance imaging; PODCI, Pediatrics Outcomes Data Collection Instrument 
a. 
See Section 7 for details on approved windows, assessments and dosing. 
b. 
Safety labs: See Section 7.2.7.1. Central labs are required at visits noted in this table. 
c. 
Vital signs (pulse, respiration, sitting blood pressure, and temperature) to be collected at every visit, and pre-infusion, within 15 minutes of infusion completion and within 15 minutes of 
completing the observation period. 
d. 
Weight and height (estimated from ulna length) to be measured in screening and approximately every 3 months thereafter. 
e. 
Physical exam to include assessment of subject’s ventilation use. A complete exam is required at Week 104. Other exams may be disease specific or problem oriented. 
f. 
Muscle function tests: Brooke Scale, Performance of Upper Limb, Pinch Strength Test, and Grip Test. 
g. 
Pulmonary Function Tests (PFTs): forced vital capacity, forced expiratory volume in 1 second, maximal inspiratory pressure, maximum expiratory pressure, peak expiratory flow 
rate, 
peak cough flow. 
h. 
See Appendix 5 for pharmacokinetic/human antihuman antibody/connective tissue growth factor and Exploratory Sample collection details. 
i. 
Local safety labs required prior to the MRIs and must include hematocrit.
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APPENDIX 4. SCHEDULE OF ASSESSMENTS: WEEK 106 THROUGH WEEK 210/EOS 
Assessmenta 
Treatment Period (Weeks) 
 
Safety 
Follow-up 
106, 
108, 
110, 
112, 114 
116 
118, 120, 
122, 124, 
126 
128 
130, 132, 
134, 136, 
138 
140 
142, 144, 
146, 148, 
150 
152 
154 
156 
210/ EOS 
158, 
160, 
162, 
164, 166 
168 
170, 172, 
174, 176, 
178 
180 
182, 184, 
186, 188, 
190 
192 
194, 196, 
198, 200, 
202 
204 
206 
208/EOT 
Clinical laboratory 
assessmentsb,i 
  
X 
  
X 
  
X 
  
X 
  
  
X 
Vital Signsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight/Heightd 
  
X 
  
X 
  
X 
  
X 
  
  
  
Electrocardiogram 
  
  
  
  
  
  
  
  
  
X 
  
Physical Examinatione 
  
X 
  
X 
  
X 
  
  
  
X 
  
Muscle function testsf 
  
X 
  
X 
  
X 
  
  
  
X 
  
Pulmonary function 
testsg 
  
X 
  
X 
  
X 
  
  
  
X 
  
Cardiac MRIi 
  
  
  
  
  
  
  
  
  
X 
  
Muscle MRIi 
  
  
  
  
  
  
  
  
  
X 
  
Specialty labsh 
  
  
  
  
  
  
  
  
  
X 
X 
Pamrevlumab infusion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 Xj 
  
Adverse Events & 
Concomitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PODCI Quality Outcome 
Questionnaire 
  
  
  
  
  
  
  
  
  
X 
  
Abbreviations: MRI, magnetic resonance imaging; PODCI, Pediatrics Outcomes Data Collection Instrument 
a. See Section 7 for details on approved windows, assessments and dosing. 
b. Safety labs: See Section 7.2.7.1. Central labs are required at visits noted in this table. 
c. Vital signs (pulse, respiration, sitting blood pressure, and temperature) to be collected at every visit, and pre-infusion, within 15 minutes of infusion completion and within 15 minutes of 
completing the observation period. 
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d. Weight and height (estimated from ulna length) to be measured in screening and approximately every 3 months thereafter. 
e. Physical exam to include assessment of subject’s ventilation use. A complete exam is required at Week 208/EOT. Other exams may be disease specific or problem oriented. 
f. Muscle function tests: Brooke Scale, Performance of Upper Limb, Pinch Strength Test, and Grip Test. 
g. Pulmonary Function Tests (PFTs): forced vital capacity, forced expiratory volume in 1 second, maximal inspiratory pressure, maximum expiratory pressure, peak expiratory flow 
rate, 
peak cough flow. 
h. See Section 5  for pharmacokinetic/human antihuman antibody/connective tissue growth factor and Exploratory Sample collection details. 
i. Local safety labs required prior to the MRIs and must include hematocrit. 
j. Pamrevlumab infusion is administered at Week 156, but is NOT to be administered at week 208/EOT.   
 
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APPENDIX 5. SPECIALTY LAB SCHEDULE 
  
  
Treatment Period 
Safety 
Follow-up 
Sample 
Timepoint 
Day  
0 
Day 
2 ±1 
day 
Day 
4 ±1 
day 
Day 
7 ±1 
day 
Day 
10±1 
day 
Week 
2 
Week 
26 
Week 
52 
Week 
104, 156, 
208 
/EOT 
Week 
210/EOS 
(4 wks 
post last 
dose) 
Pamrevlumab Pka 
Before infusion 
X 
  
  
  
  
X 
X 
X 
  
  
Within 1 hour after infusion 
X 
  
  
  
  
  
  
X 
  
  
Time point sample (no 
infusion) 
  
X 
X 
X 
X 
  
  
  
  
  
HAHAb 
Predose (when applicable) 
X 
  
  
  
  
  
  
  
  
X 
CTGFc 
Predose (when applicable) 
X 
  
  
  
  
  
  
  
X 
  
Exploratoryd 
Predose (when applicable) 
X 
  
  
  
  
  
  
X 
X 
  
Abbreviations: CTGF = connective tissue growth factor; ET = early termination; HAHA = human anti-human antibody; PK = pharmacokinetic 
a. Approximately 1-2 mL of blood will be collected for each measurement of pamrevlumab PK. 
b. Approximately 1 mL of blood will be collected for each measurement of HAHA. 
c. Blood and urine samples will be collected. Approximately 1 mL of blood and 0.5 mL of urine will be collected for each measurement of CTGF. 
d. Approximately 5 mL of blood will be collected for each exploratory sample. 
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APPENDIX 6. OPEN LABEL EXTENSION (OLE) 
This is an open-label, single arm extension to evaluate long-term efficacy and safety of 
pamrevlumab in DMD subjects who have been previously treated with pamrevlumab.  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 final safety and efficacy assessments with an End of 
Study 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. 
1. Endpoint 
Pulmonary assessment: 
• Annual mean change in percent predicted forced vital capacity (ppFVC%) assessed 
by spirometry. 
Performance assessments: 
• Annual mean change in the total score of Performance of Upper Limb (PUL). 
• Annual mean change the Grip strength of the hands extremities assessed by Hand 
Held Myometry (HHM). 
Cardiac assessments: 
• Annual mean change in cardiac fibrosis score assessed by Late Gadolinium 
Enhancement (LGE). 
• Annual mean change in Left Ventricular Ejection Fraction percentage (LVEF %) 
assessed by MRI. 
• Annual mean change in Myocardial Circumferential Strain [Mean Peak 
Circumferential strain (MPCS) and Global Circumferential Strain (GCS) percentage] 
assessed by cardiac MRI.  
Safety Assessments: 
• Adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests and 
discontinuation of treatment for treatment-related AEs serve as the safety assessments 
for this OLE. 
 
2. Study Enrollment  
All subjects participating in the Open Label Extension must have completed treatment through 
the primary endpoint and completed the EOT visit on the parent pamrevlumab DMD study.  The 
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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) 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. 
3. Study Visits  
All study visits will be performed in accordance with the Schedule of Assessments presented in 
Section 6. 
The dosing period begins on the first day of dosing with study treatment (Day 0), which is to be 
conducted simultaneously with, or within 7 days after the parent study EOT visit.  The dosing 
period continues 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.  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, not the Day 0 
(baseline) visit. 
Muscle or pulmonary function tests 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. 
Cardiac MRI may be performed within ±2 weeks of the specified visit. 
Subjects who complete the dosing period must have their end of treatment assessments 
performed at the Week 208/EOT visit.  The end of treatment Cardiac MRI may be performed 
any time from Week 208/EOT to Week 210/EOS/ET (End of Study / Early Termination) visit. 
Subjects who prematurely discontinue the study will be strongly encouraged to complete the 
final efficacy evaluations scheduled for Week 208/EOT as applicable, and the safety follow-up 
evaluations scheduled for the Week 210/EOS/ET visit (4 weeks following the last dose) and a 
final safety follow-up phone call 60 days (+3 days) after the last dose of pamrevlumab as per the 
schedule of assessments.. 
For all subjects, the final safety assessments should be completed at the Week 210/EOS/ET visit, 
4 weeks (±7 days) after the last dose of pamrevlumab 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. 
3.1  
Home Health Care 
FibroGen may consider the use of properly trained home health care staff to administer the 
pamrevlumab infusions in the future and corresponding study assessments during the conduct of 
the study, consistent with institutional regulations and policies. Home Health Care (HHC) is 
optional and the decision to utilize is driven by the site. Subjects who experience a significant 
infusion reaction will not be allowed to participate in HHC. Medications for the treatment of 
acute reactions, including anaphylaxis, will accompany the HHC nurse.  HHC support will only 
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be on weeks where no PFT, MFT, safety lab collection, or MRI are being conducted, but only a 
study drug infusion is occurring.   
4. Study Assessments 
All study assessments will be performed in accordance with the Schedule of Assessments 
presented in Section 6. Refer to the Laboratory Manual for details regarding laboratory sample 
collection and processing; and the Study Reference Manual for details regarding the conduct of 
functional tests and MRIs. 
Pulmonary function tests (PFTs) will be performed 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). 
Performance of the Upper Limb (PUL), and Grip Tests will be performed to assess changes in 
upper extremity strength and function. 
Imaging assessments will be performed to assess changes in Cardiac muscle fibrosis. 
A full physical examination will be performed approximately every 24 weeks.  
Vital signs (pulse, respiratory rate, sitting blood pressure, and temperature) will be collected at 
all visits. During infusion visits, vital signs will be collected prior to start of each infusion, within 
15 minutes of the end of each infusion, and within 15 minutes of the completion of the post-
infusion observation period. 
All laboratory tests will be performed at a central laboratory according to the Schedule of 
Assessments in Section 6. A Central Laboratory Manual with instructions on specimen 
collection, processing, storing, and shipping to the central laboratory will be provided to all 
participating sites. 
Local clinical laboratories will be used to assess and facilitate the management of adverse events 
and to provide usual standard of care (including blood draws required prior to MRIs). Local 
clinical laboratory data will not be collected in the study database except for hematocrit values 
provided with imaging data. 
Safety labs will be drawn at the site’s local lab prior to MRIs to ensure there is no 
contraindication to MRI. Hematocrit should be included in the local lab draw as these results are 
required to assess fibrosis and will be provided to the central imaging vendor along with the MRI 
scans. Details are included in the Imaging Manual. 
5. Statistical Considerations 
Data collected during the extension period will be summarized descriptively along with the main 
study. 
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6. OLE Schedule of Assessments: EX – Day 0 through Ex – week 210/EOS/ET
Treatment Period a 
Follow Up Period 
Day 
0 b 
Q2 WEEKS: ALL 
VISITS through Week 
206 
Q12 weeks 
through Week 
204 
(Wk 12, 24, 
36, etc.) 
Q24 Weeks 
(Wk 24, 48, 
72, etc.) 
Q52 weeks 
through Week 156 
(Wk 52, 104, 156, 
208r/EOT) 
Wk 210/ 
EOS/ET p
Final Safety 
phone call  
60 Days (+3 
days) after last 
treatment  
Informed Consent & Assent 
x 
Eligibility Assessment 
x 
Vital Signs c 
x 
x 
x 
x 
x 
x 
Chemistry & Hematology 
x 
x 
PFT / Height (ulna length) 
f,h,i 
x 
xq
Muscle Function Tests f,g
x 
x 
xq 
Physical Examination k 
x 
x 
Weight j
x 
x 
x 
Weight Based Dose 
Adjustment j 
x 
x 
x 
Cardiac  MRI d,e,f
x 
xq 
Specialty Labs o 
x 
x 
Pamrevlumab Infusion l
x 
x 
x 
x 
x 
AEs / SAEs m
x 
x 
x 
x 
x 
x 
x 
Concomitant Medications n 
x 
x 
x 
x 
x 
x 
x 
Abbreviations: AE = adverse event; ECG = electrocardiogram; ET= Early Termination; ICF = Informed Consent Form; PFTs = Pulmonary Function Test; 
a.) Visit window of ± 3 days starting at Week 2.  
b.) Day 0 to be conducted simultaneously with, or within 7 days after the parent study EOT visit. 
c.) Vital signs (pulse, respiration, sitting BP, temperature) to be collected at every visit: pre-infusion, and within 15 minutes of completion, and within 15 minutes 
of completing the observation period. 
d.) Local safety labs are required prior to MRIs and must include hematocrit. 
e.) Cardiac MRI may be performed within ±2 weeks of the specified visit 
f.) PFTs, MFTs, and MRI do not require repetition if performed within 4 weeks.    
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g.) For Non-ambulatory subjects only:  Muscle Function Tests (MFTs): Performance of Upper Limb, and Grip Test. 
h. ) Pulmonary Function Tests (PFTs): forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow rate.
i.) Height will be measured at each PFT interval using ulna length to approximate standing height until subject reaches adult height.  Adult height will be carried
forward.
j.) 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 up to
two weeks in advance.
k.) Full physical exam including chest auscultation
l.) Pamrevlumab infusion is NOT to be administered at week 208 (EOT)
m.) AEs and SAEs are collected from date of consent through EOS.
n.) Concomitant medications and nondrug therapies must be reported beginning after informed consent is obtained and ends 30 days after the last treatment.
o.) Specialty labs for HAHA (human anti-human antibody) / Neutralizing Antibody
p.) Subjects who terminate prior to Week 208/EOT should complete the Early Termination (ET) visit.
q.) Assessment required only if subject terminated study prior to Week 208
r.) 208 weeks is an estimation of maximum duration for OLE.  Actual duration of the OLE will be determined at the Sponsor’s program level.
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SAP_003.pdf: 
FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
STATISTICAL ANALYSIS PLAN 
STUDY TITLE: 
Trial of Pamrevlumab (FG-3019), a Monoclonal 
Antibody to Connective Tissue Growth Factor, in 
Non-Ambulatory Subjects with Duchenne Muscular Dystrophy 
(Open-Label Extension) 
PROTOCOL NUMBER: 
FGCL-3019-079 OLE 
Amendment 8: 18 November 2020 
SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
Version 
2.0 
Release Date: 
12 October 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. 
Confidential
Page 1 of 34
NCT #:  NCT02606136


FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
 
 
SIGNATURES AND APPROVALS 
Approvals 
I have reviewed and accepted the information in this document to be a true and accurate 
representation of the Statistical Analysis Plan. 
 
Initiator: 
 
, FibroGen, Inc. 
Reviewed By: 
 
, FibroGen, Inc. 
 
, FibroGen, Inc. 
 
, FibroGen, Inc 
  
, FibroGen, Inc. 
, FibroGen, Inc. 
 
 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
 
 
 
Signature Significance 
The following significance is lent to the signatures on the Approvals page of this document. 
 
Signatory 
Significance 
Initiator 
By signing, the author is attesting that the content of the 
document is complete and accurate. 
Reviewer 
By signing, the reviewer is attesting that the document’s approach and 
contents are compliant with the study protocol, all appropriate, 
regulatory requirements, and other significant guidelines. This 
individual(s) has 
reviewed the document for accuracy and completeness. 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
CHANGE HISTORY 
 
 
Version 
Date 
Description 
1.0 
5/2/2021 
Original Final Version 
1.1 
5/7/2021 
Minor edits 
1.2 
1/25/2023 
 Added section 11 for immunogenicity analysis 
1.3 
7/24/2023 
Major changes: 
1. Changed RCM to MMRM for all efficacy endpoints except 
for ppFVC 
2. Removed ITT and added IGS analysis population 
3. Changed Day 0 to Day 1 
4. Updated analysis windows per protocol 
 
2.0 
10/12/2023 
Final version v2.0 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.1 
 
 
TABLE OF CONTENTS 
 
 
Contents 
CHANGE HISTORY ........................................................................................................................................................ 4 
1. 
INTRODUCTION ................................................................................................................................................... 9 
1.1. 
Preface ............................................................................................................................................................... 9 
1.2. 
Purpose of the Analyses ...................................................................................................................................... 9 
2. 
STUDY DESIGN ................................................................................................................................................... 10 
3. 
STUDY OBJECTIVES ............................................................................................................................................ 11 
3.1. 
Primary Objective ............................................................................................................................................. 11 
4. 
STUDY ENDPOINTS ............................................................................................................................................ 12 
4.1. 
Efficacy Endpoints ............................................................................................................................................ 12 
4.2. 
Safety Assessments .......................................................................................................................................... 12 
5. 
GENERAL STATISTICAL CONSIDERATIONS .......................................................................................................... 13 
5.1. 
Statistical Methodology .................................................................................................................................... 13 
5.2. 
Analysis Populations ......................................................................................................................................... 13 
5.2.1. 
Safety Population (SAF-OLE) .................................................................................................................... 13 
5.2.2. 
Immunogenicity Analysis Set (IGS) .......................................................................................................... 13 
5.3. 
Handling of Dropouts or Missing Data ............................................................................................................. 13 
5.4. 
Additional Data Handling Rules and Presentation Specifications ...................................................................... 14 
5.4.1. 
Handling Missing/Incomplete AE Onset Date ......................................................................................... 14 
5.4.2. 
Handling Missing/Incomplete Concomitant Medication Start/Stop Dates ............................................ 14 
5.4.3. 
Definition of Baseline ............................................................................................................................... 14 
5.5. 
Analysis Visit Windows ..................................................................................................................................... 15 
5.6. 
Protocol Deviations .......................................................................................................................................... 15 
6. 
SUBJECT ACCOUNTABILITY AND DISPOSITION ................................................................................................... 16 
7. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS ........................................................................................... 17 
7.1. 
Demographics and Baseline Characteristics ...................................................................................................... 17 
7.2. 
Medical History ................................................................................................................................................. 17 
8. 
TREATMENTS AND MEDICATIONS ..................................................................................................................... 18 
8.1. 
Study Drug Exposure ......................................................................................................................................... 18 
8.2. 
Concomitant Medications ................................................................................................................................ 18 
9. 
EFFICACY ANALYSIS ........................................................................................................................................... 19 
9.1. 
Efficacy Endpoints ............................................................................................................................................ 19 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.1 
 
 
9.2. 
Analysis Methods for Efficacy Endpoints ........................................................................................................... 19 
9.2.1. 
Descriptive Summary ............................................................................................................................... 20 
9.2.2. 
Annual Change from Baseline to Week 208 in Efficacy Endpoints with RCM ............................................... 20 
9.2.3. 
Change from Baseline in Efficacy Endpoints with MMRM ........................................................................... 21 
9.2.4. 
Exploratory Analysis - Comparison with the CINRG natural history data................................................ 22 
10. 
SAFETY ANALYSIS .......................................................................................................................................... 23 
10.1. 
Adverse Events .................................................................................................................................................. 23 
10.2. 
Clinical Laboratory Assessments ....................................................................................................................... 24 
10.3. 
Vital Signs ......................................................................................................................................................... 24 
10.4. 
Physical Examination ........................................................................................................................................ 24 
10.5. 
Electrocardiogram ............................................................................................................................................ 24 
10.6. 
Special Safety Events ........................................................................................................................................ 24 
11. 
INTERIM ANALYSIS ........................................................................................................................................ 25 
12. 
IMMUNOGENICITY ANALYSIS ........................................................................................................................ 26 
12.1. 
Terms and Definitions ...................................................................................................................................... 26 
12.1.1. 
Sample ADA Status: ................................................................................................................................. 26 
12.1.2. 
Subject ADA Status: ................................................................................................................................. 26 
12.2. 
Statistical Analysis for Characterization of ADA Immune Response ................................................................ 27 
12.2.1. 
Incidence of ADA ..................................................................................................................................... 27 
12.2.2. 
ADA Titer Kinetics .................................................................................................................................... 27 
13. 
CHANGES FROM PROTOCOL.......................................................................................................................... 28 
14. 
REFERENCES .................................................................................................................................................. 29 
15. 
APPENDICES .................................................................................................................................................. 30 
APPENDIX 1. Analysis Visit Windows ......................................................................................................................... 31 
APPENDIX 2. Sample SAS Code for RCM analysis ....................................................................................................... 34 
 
 
 
 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.1 
 
 
List of Abbreviations 
 
 
 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BIW 
Twice weekly 
BP 
Blood Pressure 
CBC 
Complete blood count 
CKD 
Chronic kidney disease 
CRF 
Case report form 
COVID-19 
Coronavirus disease 2019 
CRP 
C-Reactive Protein 
DBP 
Diastolic Blood Pressure 
ECG 
Electrocardiogram 
EE 
Efficacy Evaluable 
eGFR 
Estimated glomerular filtration rate 
ELISA 
Enzyme-Linked Immunosorbent Assay 
EOT 
End of Treatment 
EOS 
End of Study 
EPO 
Erythropoietin 
HIV 
Human immunodeficiency virus 
HMP 
Hepatic Monitoring Plan 
HR 
Heart Rate 
IV 
Intravenous 
LLN 
Lower Limit of Normal for a lab parameter 
MAP 
Mean Arterial Pressure 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEP 
Maximal expiratory pressure 
MIF50 
Maximal inspiratory flow at 50% 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.1 
 
 
 
MIP 
Maximal inspiratory pressure 
mg 
Milligram 
MMRM 
Mixed Model Repeated Measures 
MRI 
Magnetic resonance imaging 
NCI 
National Cancer Institute 
NCS 
Not clinically significant 
NYHA 
New York Heart Association 
OLE 
Open label extension 
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 
ROM 
Range of motion 
RPM 
Respirations per minute 
RCM 
Random coefficient model 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SE 
Standard error 
SOC 
System organ class 
SDTM 
Study Data Tabulation Model 
TEAE 
Treatment emergent adverse event 
TLFs 
Tables, listings and figures 
ULN 
Upper limit of normal 
WHODrug 
World Health Organization Drug Dictionary 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
1. 
INTRODUCTION 
1.1. 
Preface 
This study is a single-arm, open-label extension (OLE) of Study FGCL-3019-079. The OLE period 
was designed to evaluate the long-term efficacy and safety of pamrevlumab in non-ambulatory 
DMD subjects who participated in the main phase of the study. Each subject in the OLE will receive 
pamrevlumab (35 mg/kg) intravenously (IV), every 2 weeks (Q2W) for up to 208 weeks. This dose 
was a continuation of the dose regimen evaluated during the main study period of FGCL-3019-079. 
At completion of the OLE subjects will be asked to return to the investigative site to complete final 
assessments with an End of Study (EoS) visit. 
The parent study protocol FGCL-3019-079 provides detailed information on study drug formulation, 
storage, and administration. 
This statistical analysis plan (SAP) summarizes statistical analyses of study data for the subjects 
who participated in the OLE period of Study FGCL-3019-079.  
1.2. 
Purpose of the Analyses 
The analyses will evaluate the long-term efficacy and safety of pamrevlumab in non-ambulatory 
DMD subjects who participated in the OLE period following completion of pamrevlumab treatment 
in the main period of FGCL-3019-079. 
The OLE data will be summarized as part of the Study FGCL-3019-079 clinical study report. 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
2. 
STUDY DESIGN 
This study is designed as the open-label extension (OLE) of the main study FGCL-3019-079. All 
subjects participating in the OLE must have completed treatment through the primary endpoint and 
completed the End of Treatment (EOT) visit of the main study FGCL-3019-079. 
Each subject in the OLE receives pamrevlumab (35 mg/kg, every 2 weeks) for up to 208 weeks. The 
dosing period began on the first day of dosing with study treatment (Day 1) in the OLE, which is to 
be conducted simultaneously with, or within 7 days after the parent study EOT visit. The dosing 
period continued until Week 208/EOT. 
 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
3. 
STUDY OBJECTIVES 
3.1. 
Primary Objective 
The primary objective of this trial is to evaluate long-term efficacy and safety of pamrevlumab 
in non-ambulatory DMD subjects who have been previously treated with pamrevlumab for a 
minimum of 104 weeks. 
 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
4. 
STUDY ENDPOINTS 
4.1. 
Efficacy Endpoints 
The efficacy endpoints are: 
Pulmonary assessment: 
• Annual mean change in percent predicted forced vital capacity (ppFVC%) assessed by 
spirometry. 
 
Performance assessments: 
• Annual mean change from baseline in the total score of Performance of Upper Limb 
(PUL). 
• Annual mean change from baseline in the grip strength of the hands extremities assessed 
by Hand Held Myometry (HHM) 
 
Cardiac assessments: 
• Annual mean change from baseline in cardiac fibrosis score assessed by Late Gadolinium 
Enhancement (LGE) 
• Annual mean change from baseline in Left Ventricular Ejection Fraction percentage 
(LVEF %) assessed by MRI 
• Annual mean change from baseline in Myocardial Circumferential Strain [Mean Peak 
Circumferential strain (MPCS) and Global Circumferential Strain (GCS) percentage] 
assessed by cardiac MRI 
4.2. 
Safety Assessments 
Treatment emergent adverse events (TEAEs), serious adverse events (SAEs), clinical laboratory 
tests and discontinuation of treatment for treatment-related TEAEs serve as the safety assessments for 
this OLE. 
 
 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
5. 
GENERAL STATISTICAL CONSIDERATIONS 
5.1. 
Statistical Methodology 
Continuous variables will be presented by descriptive statistics: n, mean, standard deviation, 
median, Q1-Q3, minimum, and maximum. Categorical variables will be tabulated by frequency 
count and percentage. 
Lab results obtained from the central laboratory, rather than local laboratories, will be used for all 
efficacy and safety analyses. Some lab data are collected using local labs (in lieu of the ICON 
central lab) due to central lab kit shortages caused by the COVID-19 pandemic. In these cases, local 
lab values and reference ranges collected from CRFs will be integrated with central lab data when 
appropriate and feasible. Local lab values will be flagged in data sets and data listings to be 
differentiated from central lab values. Sensitivity analyses may be performed for key analyses of lab 
parameters without local lab values (e.g., set to missing). 
Unless otherwise stated, all statistical tests will be two-sided hypothesis tests performed at the 5% 
level of significance for main effects and all confidence intervals will be two-sided 95% confidence 
intervals. 
Unless otherwise specified, there will be no adjustments for multiple comparisons. 
All data collected will be presented by data listings for review and substantiation of summary tables. 
Safety and efficacy data will be summarized and presented by treatment group (pamrevlumab or 
source of external data, as applicable), and analysis visit in summary tables as appropriate. 
All analyses will be performed using SAS® Version 9.4 or higher. 
5.2. 
Analysis Populations 
5.2.1. 
Safety Population (SAF-OLE) 
The Safety population of OLE period (SAF-OLE) consists of all subjects who received at least one 
dose of study drug in the OLE period. The SAF population will be used in the analyses of all safety 
parameters. 
All analyses for OLE period will be based on SAF-OLE if not specified otherwise. 
5.2.2. 
Immunogenicity Analysis Set (IGS) 
The Immunogenicity Analysis Set (IGS) contains all the Anti-Drug Antibody and/or Neutralizing 
Antibody (ADA/NAb) evaluable patients, who are in the SAF analysis set with at least one 
ADA/NAb sample (with reportable results) taken pre-treatment (i.e., a baseline sample) and at least 
one ADA/NAb sample (with reportable result) taken post-treatment in the OLE period. 
5.3. 
Handling of Dropouts or Missing Data 
All analyses will be based on observed data; missing data will not be imputed. 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
5.4. 
Additional Data Handling Rules and Presentation Specifications 
5.4.1. 
Handling Missing/Incomplete AE Onset Date 
If the AE onset date is incomplete or missing, the following rules will be applied to impute AE onset 
date. 
• If year and month are present, only day is missing, 
a. If AE onset Year/month = Day 1 Year/month, assign onset day = day part of Day 1 (Day 
1 is the first infusion day); 
b. If AE onset Year/month ≠ Day 1 Year/month, assign onset day = 1st of the month. 
• If year is present, month and day are missing, or when only month is missing (treating day 
as missing), 
a. If AE onset year = year of Day 1, assign onset date = month and day part of Day 1 date. 
b. If AE onset year ≠ year of Day 1, assign onset date= January 1st. 
• If onset date is completely missing, assign onset date = date of Day 1. 
If the stop date is complete and the imputed start date as above is after the stop date, the start date 
will be imputed by the stop date. 
5.4.2. 
Handling Missing/Incomplete Concomitant Medication Start/Stop Dates 
For concomitant medications, including rescue medications, incomplete (i.e., partially missing) start 
date is imputed the same way as for the AE described above. When the start date and the stop date 
are both incomplete for a patient, impute the start date first. 
Incomplete Stop Date 
The following rules are applied to impute the missing stop date, if needed. 
• If year is present, month and day are missing, or when only month is missing (treating 
day as missing) 
a. If CM stop year = year of last dose, assign stop date = month and day part of of last dose 
date; 
b. If CM stop year ≠ year of last dose, assign stop date= December 31st. 
• If year and month are present, only day is missing, 
a. If CM stop Year/month = Year/month of last dose date, assign stop day = day part of last 
dose date 
b. If CM stop Year/month ≠ year of last dose, assign onset day = last day of the month. 
• Impute CM end date even if ‘ONGOING’ is checked to report the CM treatment duration 
in the study if needed. 
5.4.3. 
Definition of Baseline 
• Baseline for the OLE period is the acceptable value from the last visit on or before the first 
dose date in OLE. 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
• Baseline for main study period is defined the same as in SAP for the main study period.  
5.5. 
Analysis Visit Windows 
Efficacy parameters will be summarized by analysis visit defined by the following assessment 
windows (Section 15). The date of the first dose will be considered as the date of Day 1 for all 
analysis. The analysis visit window for some safety assessments such as lab tests and vital signs are 
also defined in the same section. 
5.6. 
Protocol Deviations 
Protocol deviations of interest may include, but are not limited to, the following: 
• Subjects who did not meet inclusion/exclusion criteria 
• Subjects who received disallowed concomitant medications or non-drug therapy 
• Subjects who missed important assessments or did not attend a visit as planned 
• Subjects who did not receive adequate dosing. 
The number and percentage of important protocol deviations will be categorized and tabulated as 
appropriate. 
 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
6. 
SUBJECT ACCOUNTABILITY AND DISPOSITION 
The number and percentage of subjects who are dosed, completed the treatment or study, and 
prematurely discontinued will be summarized for the Safety Population. 
Reasons for premature discontinuation as recorded on the Study Disposition page of the CRF will be 
summarized by number and percentage. 
All subjects of the Safety Population, including subjects who discontinue prematurely from the 
study, will be listed with their treatment group, date and time of first and last dose, days in 
treatment, date of last visit, and reason for discontinuation. 
A separate listing for the subjects who discontinue prematurely, date and time of first and last dose, 
days in treatment, date of last visit, and reason for discontinuation will be presented. 
 
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FGCL-3019-079 OLE 
Statistical Analysis Plan, Version 1.3 
 
 
7. 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
7.1. 
Demographics and Baseline Characteristics 
Subject demographics, baseline characteristics, baseline disease characteristics, and baseline 
efficacy measures will be summarized. Baseline disease characteristics include general medical 
history, disease specific characteristics, and prior treatments. Baseline efficacy measures include PFT 
parameters, hand and arm functions, cardiac and muscle MRI parameters. 
Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) will be 
presented for continuous variables. In addition, 25%-75% values of Biomarker will be presented. 
Frequency distributions (number and percentage of subjects) will be presented for categorical 
variables. 
Descriptive statistics of baseline values for other parameters will be presented in their change from 
baseline tables. 
Demographics and baseline characteristics of the study will be summarized using descriptive 
statistics. 
Demographic variables will include age in years, sex (optional as all DMD subjects are male), race, 
and ethnicity. Age at baseline is defined as the age when signing inform consent: 
 
age = Year of Date of Informed Consent – Birth year. 
Other baseline characteristics include height, weight, side of dominant hand, BSA, and body mass 
index (BMI). 
Computation formulas: 
BSA = [Weight 0.425 (kg) * Height 0.725 (cm)] x 0.007184 
BMI = Weight (kg) / (Height (m))2 
7.2. 
Medical History 
Medical history, including allergies and surgeries, will be tabulated in system organ class (SOC) and 
preferred term (PT) using MedDRA version 26.0 or higher. 
 
 
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8. 
TREATMENTS AND MEDICATIONS 
8.1. 
Study Drug Exposure 
The number and percentage of subjects who receive study medication will be summarized. 
Duration in weeks from first infusion to last infusion, calculated as (last dose date – first dose 
date+1)/7, will be summarized by the categories as follows: 
<= 26 weeks 
>26 weeks to <=52 weeks 
>52 weeks to <=78 weeks 
>78 weeks to <=104 weeks 
>104 weeks to <=156 weeks 
>156 weeks to <=208 weeks 
>208 weeks 
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. 
The compliance will be presented as % of actual doses of infusion administered out of the expected 
total dose of infusions during study. Compliance = (actual doses received / expected doses during 
study) * 100%. Treatment compliance will be summarized as a continuous variable and as a categorical 
variable (<70%, 70% -<80%, 80% - 90%, and >90%). 
Duration of exposure, weekly exposure and total study drug exposure will be tabulated. 
8.2. 
Concomitant Medications 
The historical use of the medications is summarized using descriptive statistics for the Safety 
population. 
Medications recorded on the Concomitant Medication CRF are classified in the analysis dataset in 
the following categories: 
• Concomitant medications - medications that are used concomitantly with the study drug, 
which are defined as medications that were not stopped before the first infusion. 
• Use of corticosteroids 
Concomitant medications are summarized by ATC class and preferred term . Subjects reporting 
more than one use of the same medication will be counted only once in the summary tables. 
All medications captured in Concomitant Medication CRF, as well as Non-Drug Therapies CRF are 
presented in data listings. 
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9. 
EFFICACY ANALYSIS 
9.1. 
Efficacy Endpoints 
The Efficacy Endpoints are: 
Pulmonary assessment: 
• Annual mean change in percent predicted forced vital capacity (ppFVC%) assessed by 
spirometry. 
Performance assessments: 
• Annual mean change from baseline in the total score of Performance of Upper Limb 
(PUL). 
• Annual mean change from baseline the Grip strength of the hands extremities assessed by 
Hand Held Myometry (HHM). 
Cardiac assessments: 
• Annual mean change from baseline in cardiac fibrosis score assessed by Late Gadolinium 
Enhancement (LGE). 
• Annual mean change from baseline in Left Ventricular Ejection Fraction percentage 
(LVEF %) assessed by MRI. 
• Annual mean change from baseline in Myocardial Circumferential Strain [Mean Peak 
Circumferential strain (MPCS) and Global Circumferential Strain (GCS) percentage] 
assessed by cardiac MRI. 
 In addition to the analysis of annual mean changes of the above efficacy endpoints with random 
coefficient model (RCM), the change from baseline in the following efficacy endpoints of PUL, grip 
strength, LVEF%, and cardiac MRIs including cardiac fibrosis score assessed by Late Gadolinium 
Enhancement (LGE), and Myocardial Circumferential Strain [Global Circumferential Strain (GCS)], 
will be analyzed with Mixed Model for Repeated Measures (MMRM) at Week 48/52, Week 96/104, 
Week 144/156, and Week 192/208 per the schedule, without assuming linear trajectories by disease 
progression. 
9.2. 
Analysis Methods for Efficacy Endpoints 
Unless otherwise noted, long-term treatment effects of all efficacy endpoints at each timepoint will 
be summarized and analyzed from the baseline of the main study through the last visit in the 
extension phase. Change from baseline values in efficacy endpoints will be analyzed with MMRM 
Annual rate of change from baseline using Random Coefficient Model (RCM) analysis, and the 
estimated change from baseline values at year 1 through year 4 described in the following sub-
sections will be presented. 
The sponsor will conduct an exploratory comparison of disease progression of FGCL-3019-079 
clinical trial participants with natural history data of patients with non-ambulatory DMD.  If 
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warranted, analyses adjusting for matching on established baseline prognostic factors will be 
conducted under a separate SAP. 
9.2.1. 
Descriptive Summary 
Continuous variables will be presented by descriptive statistics: n, mean, standard deviation (SD), 
standard error (SE), median, 25th and 75th percentile, minimum, and maximum. The 2- sided 95% 
confidence interval for the mean and median will be presented as appropriate. 
Categorical variables will be tabulated by frequency count and percentage. The confidence interval 
for the proportions for each will be calculated using the Clopper-Pearson method as appropriate. 
9.2.2. 
Annual Change from Baseline to Week 208 in Efficacy Endpoints with RCM 
The following endpoints will be analyzed with the same RCM analysis method. 
1. Annual mean change from baseline in the Percent Predicted FVC (ppFVC) 
2. Annual mean change from baseline in the total score of Performance of Upper Limb (PUL) 
3. Annual mean change from baseline the Grip strength of the hands extremities assessed by 
Hand Held Myometry (HHM) 
4. Annual mean change from baseline in cardiac fibrosis score assessed by Late Gadolinium 
Enhancement (LGE) 
5. Annual mean change from baseline in Left Ventricular Ejection Fraction percentage (LVEF 
%) assessed by MRI 
6. Annual mean change from baseline in Myocardial Circumferential Strain [Mean Peak 
Circumferential strain (MPCS) and Global Circumferential Strain (GCS) percentage] 
assessed by cardiac MRI 
9.2.2.1. 
Analysis Method 
Annual mean change from baseline in the above efficacy endpoints each will be analyzed using 
Random Coefficient Model (RCM) analysis, and the estimated annual change from baseline values 
at year 1 through year 4 in the OLE period will be presented.  
The model will include continuous variable avisityr (calculated as the elapsed days of assessment 
date from baseline date in the unit of year) and baseline endpoint as fixed effects, while the intercept 
and avisityr are  included as random effects. 
The unstructured covariance structure for the within-patient errors in the model will be applied first. 
The by-treatment-group option is included to the covariance pattern to improve the model 
efficiency. 
If the algorithm for unstructured covariance pattern does not converge, the following covariance 
structures will be tested in sequence until the model converges: heterogeneous Toeplitz, 
homogeneous Toeplitz, first-order autoregressive, compound symmetry, and variance component. 
The sandwich estimator will be used if there is convergence issue. If the model does not converge 
for all covariance structures listed above, some least significant factors or interaction terms (p>0.05) 
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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.  
When the random effects model does not converge or do not have a positive definite Hessian, the 
fixed effects instead of random effects for the intercept and slope will be performed instead. 
The LSMean (SE) and 95% CI for annual change (slope) as well as estimated changes from baseline 
at year-1, year 2, year 3 and year 4 (regarding week 52, week 104, week 156 and week 208) will be 
presented. 
9.2.2.2. 
Handling of Intercurrent Events: 
Treatment discontinuation (such as: due to AEs, Lost to Follow-Up, Withdrawal by subject, 
Physician Decision, Protocol Deviations, etc.): treatment policy: the occurrence of the intercurrent 
event is irrelevant. All observed values will be used regardless of whether or not the inter-current 
event occurs.  
9.2.3. 
Change from Baseline in Efficacy Endpoints with MMRM 
The following efficacy endpoints will be analyzed with MMRM method. 
1. At Week 48, Week 96, Week 144, and Week 192 
a. Change from baseline in PUL total score, including middle and distal score  
b. Change from baseline in grip strength. The grip strength should be reported by dominant 
and non-dominant hand separately. 
2. At Week 52, Week 104, Week 156, and Week 208 
a. Change from baseline in LVEF% 
b. Change from baseline in cardiac MRIs including cardiac fibrosis score assessed by Late 
Gadolinium Enhancement (LGE) 
c. Change from baseline in Myocardial Circumferential Strain [Global Circumferential 
Strain (GCS)] 
9.2.3.1. 
Analysis Method 
The observed and change from baseline in the above efficacy endpoints each will be summarized by 
analysis visit and analyzed using MMRM with visit, baseline, and age with appropriate covariance 
matrix for the within subject covariance over time.  
If the algorithm for unstructured covariance pattern does not converge, the following covariance 
structures will be tested in sequence until the model converges: heterogeneous Toeplitz, 
homogeneous Toeplitz, first-order autoregressive, compound symmetry, and variance component. 
The sandwich estimator will be used if there is convergence issue. If the model does not converge 
for all covariance structures listed above, some least significant factors or interaction terms (p>0.05) 
can be excluded from the model to achieve convergence. The revised model with fewer factors or 
interaction terms will be tested using the same sequence as specified above. 
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9.2.3.2. 
Handling of Intercurrent Events: 
Treatment discontinuation (such as: due to AEs, Lost to Follow-Up, Withdrawal by subject, 
Physician Decision, Protocol Deviations, etc.): treatment policy: the occurrence of the intercurrent 
event is irrelevant. All observed values will be used regardless of whether the inter-current event 
occurs.  
9.2.4. 
Exploratory Analysis - Comparison with the CINRG natural history data 
Efficacy endpoints: % predicted FCV (ppFVC), LVEF, and grip strength in dominant hand will be 
compared with a subset of CINRG DMD Natural History study (DNHS) data with all 36 subjects 
using a random coefficient model (RCM). The other outcome measures including Performance of 
Upper Limb (PUL), cardiac fibrosis by LGE, and Myocardial Circumferential Strain [Mean Peak 
Circumferential strain (MPCS) and Global Circumferential Strain (GCS) percentage] assessed by 
cardiac MRI are not available in CINRG data and therefore will not be compared.. The RCM model 
will use efficacy data from both the main and OLE periods and include continuous variable avisityr 
(calculated as the elapsed days of assessment date from main study baseline date in the unit of year), 
treatment trt (079 subjects as treated with trt = 1, and subjects in CINRG data as control with trt =0), 
the interaction term of trt and avisityr, and baseline endpoint as fixed effects, while the intercept and 
avisityr are included as random effects. The strategy for covariance structure for the within-patient 
errors in the model is the same as what is described in Section 9.2.2.1. The LSMean (SE) for annual 
change (slope) as well as LSMean (SE) and 95% CI of treatment differences between pamrevlumab 
and control of estimated changes from baseline at year 1, year 2, year 3 and year 4 in the OLE 
period will be presented. The sample SAS code is provided in Appendix 2. 
Line plots of each subject’s efficacy trajectory compared with the mean plot of the CINRG will be 
provided. 
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10. 
SAFETY ANALYSIS 
10.1. 
Adverse Events 
All reported AEs will be presented in listings. For the OLE period of the  3019-079 study, the 
treatment emergent period of safety reporting for the Clinical Study Report (CSR) is defined as from 
the first infusion date to the last infusion date + min (60 days, EOS date -last infusion date+1) for 
those subjects in  the open label extension (OLE) period. 
Number (%) of subjects with a treatment emergent adverse events (TEAEs) in the treatment 
emergent period of safety reporting (OLE period) will be summarized by system organ class (SOC) 
and preferred term (PT). The summary tables will be sorted alphabetically by SOC and by 
decreasing order of frequency of PT within each SOC. A subject with multiple adverse events 
within a SOC is only counted once in this SOC. Similarly, a subject with multiple adverse events 
within a PT is only counted once in this PT. 
The exposure adjusted incidence rate, number of subjects with the event/total patient exposure years 
(PEY)*100, will be summarized, system organ class (SOC) and preferred term (PT). 
The patient exposure years (PEY), (last infusion date – first infusion date + 1)/365.25, for each 
subject will be summed to calculate the total patient exposure years. The summary tables will be 
sorted alphabetically by SOC and by decreasing order of frequency of PT within each SOC. A 
subject with multiple adverse events within a SOC is only counted once in this SOC. Similarly, a 
subject with multiple adverse events within a PT is only counted once in this PT. In addition to 
listing of all reported AEs and summary of all TEAEs, the following TEAE summaries will be 
provided: 
• TEAEs 
• TEAEs (grade 3 and higher per CTCAE) 
• TEAE leading to treatment discontinuation 
• TEAE and relationship to FG-3019 (pamrevlumab) 
• TEAE and severity 
• TESAE and relationship to FG-3019 (pamrevlumab) 
• Most frequent (non-serious) TEAEs (>=5%) 
• Listing of Deaths 
• Listing of Serious Adverse Events 
• Listing of TEAE leading to treatment discontinuation 
In addition, special safety events such as hypersensitivity, anaphylactic and infusion reactions will 
be included. 
 
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10.2. 
Clinical Laboratory Assessments 
Blood samples are drawn for the following analyses: complete blood count, gamma glutamyl 
transferase (GGT), total bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), 
alanine transaminase (ALT), and albumin, creatine kinase (CK), and cystatin C. 
Laboratory test results and change from baseline are summarized by analysis visit. 
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 categories are tabulated. 
Shift from baseline to most severe CTCAE category during the study is also summarized. 
The Baseline for the laboratory parameters will be taking from EOS Laboratory value of the Parent 
study 079. 
Laboratory values out of normal range, in particular, panic laboratory parameter / values will be 
listed. 
10.3. 
Vital Signs 
Pulse (beat/min), diastolic and systolic blood pressure (mmHg), respiration (breaths/min), and 
temperature (C) will be summarized for selected analysis visit. 
10.4. 
Physical Examination 
Physical examination results (complete and targeted) will be listed by subject, visit, and body 
system. 
10.5. 
Electrocardiogram 
Number (%) of subjects with ECG results (normal/abnormal/Clinically Significant) will be 
summarized by analysis visit. 
10.6. 
Special Safety Events  
Treatment-emergent special safety events including:  
1. Hypersensitivity (any time)  
2. Infusion reactions (on day of infusion or 1 day post any study drug infusion) 
3. Anaphylactic reactions (on day of infusion or 1 day post any study drug infusion) 
Items 1 and 2 include both hypersensitivity and angioedema events. Both items will be listed and 
summarized similarly to TEAEs.  
Items 3 uses a modified SMQ to retrieve events under anaphylactic reactions and will be listed and 
summarized by treatment and PT only.   
The preferred term list for these special safety events will be finalized prior to database lock. 
 
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11. 
INTERIM ANALYSIS 
Not applicable. 
 
 
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12. 
IMMUNOGENICITY ANALYSIS  
Analysis of immunogenicity data will be based on IGS.  Analysis dataset and data listing will 
include all available Human Anti-Human Antibody (HAHA, ADA) samples. The following terms 
and definitions are implemented. 
12.1. 
Terms and Definitions 
12.1.1. 
Sample ADA Status: 
• Baseline ADA-positive sample: ADA is detected in the last sample before initiation of 
treatment. 
• Baseline ADA-negative sample: ADA is not detected in the last sample before initiation 
of treatment. 
• Treatment-emergent ADA-Positive: Meets definition of treatment-induced or 
treatment-boosted ADA. After initiation of treatment,  
− Treatment-induced ADA-Positive: a post-treatment positive ADA is detected in a 
subject for whom pre-treatment ADA assessment is either negative or not assessable, 
or  
− Treatment-boosted ADA-Positive: pre-existing ADA were boosted to a higher level 
following study treatment, i.e. pre-treatment positive ADA titer was boosted by at 
least 2 dilution steps (4-fold) following study treatment. 
• ADA-negative sample: After initiation of treatment, ADA is not ADA-positive sample 
relative to baseline. 
Next, using the sample ADA status, subject ADA status is defined. 
12.1.2. 
Subject ADA Status: 
• Baseline ADA-positive subject: A subject with baseline ADA-positive sample.  
• ADA-positive subject:  An evaluable subject with at least one treatment-emergent ADA 
sample at any time during the study. 
• Neutralizing-positive: At least one treatment-emergent ADA-positive sample with 
neutralizing antibodies detected (if available). 
• ADA-negative subject: An evaluable patient without a treatment-emergent ADA- 
positive sample during the study. 
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12.2. 
Statistical Analysis for Characterization of ADA Immune Response 
12.2.1. 
Incidence of ADA 
• Percentage of treatment-emergent ADA patients for the defined study period, where the 
denominator is the number of ADA evaluable patients in the respective treatment arm 
and/or subgroup. 
• Number (%) of subjects will be reported for the following parameters based on evaluable 
subjects: 
• Baseline ADA-positive 
• ADA-positive (Treatment-induced, Treatment-boosted) 
• Neutralizing Positive (if available) 
• ADA-negative 
• ADA prevalence: Percentage of treatment-emergent ADA patients at any given 
timepoint, where the denominator is the number of ADA evaluable patients in the 
respective treatment arm and/or subgroup at that timepoint. 
• A listing of all ADA assessments will be provided.  
• Additionally, a separate listing of ADA assessments for all neutralizing antibody (NAb)-
positive subjects will be provided (if available). 
12.2.2. 
ADA Titer Kinetics  
All ADA-positive subjects will be included in the analysis. 
• Summary statistics of subject-level ADA titers using the maximum titer value within an 
ADA positive subject will be presented for baseline ADA-negative subjects and baseline 
ADA positive subjects. The median, interquartile range, and range of the maximum titers 
will be reported. For ADA-positive subjects with baseline ADA-positive sample, the 
median and interquartile range of the fold increase from baseline in titer (ratio of 
maximum post-baseline titer to baseline titer) will also be reported. Graphical 
presentation of the summary data may be provided using boxplots, as appropriate. 
• For sample-level ADA titers, boxplots of ADA titers at each assessment timepoint will 
be provided, as appropriate, to demonstrate whether the ADA levels tend to change over 
time during the treatment, along with ADA incidence at each assessment timepoint. 
• Spider plots may be considered to show the trend of ADA titer over time for subjects 
with >/= 5 ADA results by splitting subjects into multiple spider plots (eg, ≈ ≤10 per 
plot, approximately. 
 
 
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13. 
CHANGES FROM PROTOCOL 
• The date of the first dose in the OLE period will be considered as the date of Day 1 for 
all analyses during the OLE period, instead of Day 0. 
• Efficacy parameters, including change from baseline of the main study in ppFVC, PUL, 
grip strength, LVEF%, and cardiac MRIs including cardiac fibrosis score assessed by 
Late Gadolinium Enhancement (LGE), and Myocardial Circumferential Strain [Global 
Circumferential Strain (GCS)], will be analyzed at Week 48/52, Week 96/104, etc. in the 
OLE period using Mixed Model for Repeated Measures (MMRM) additionally. 
 
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14. 
REFERENCES 
1. Mayhew A, Mazzone ES, Eagle M, et al. Development of the Performance of the Upper 
Limb module for Duchenne muscular dystrophy. Dev Med Child Neurol 2013;55:1038–45. 
2. Pane M, Mazzone ES, Fanelli L, et al. Reliability of the Performance of Upper Limb 
assessment in Duchenne muscular dystrophy. Neuromusc Disord 2014;24:201-206. 
3. Hankinson JL, Odencrantz JR, Fedan KB, Spirometric reference values from a sample of the 
general U.S. population. Am J Respir Crit Care Med 1999; 159:179 – 187. 
4. Mayer OH, Finkel RS, Rummey C et al. Characterization of Pulmonary Function in 
Duchenne Muscular Dystrophy. Pediatr Pulmonol. 2015; 50:487–494 
 
 
 
 
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15. 
APPENDICES 
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APPENDIX 1. ANALYSIS VISIT WINDOWS 
 
Table 1: Assessment Windows for PFT 
 
 
Analysis Visit 
Window 
Baseline 
 Value at the visit on or prior to the first dose of 
study drug 
Target day=1, window = [L0, H0] = [--,1] 
Week X 
X = 24*K, k=1, 2, …, 7 
Target day = 7 * X + 1 
Window = [LK, HK] = [HK-1+1, Target Day+24*7/2-1] 
Week 192 
[L8  = H7 +1 = 1261, **] 
** There will be no upper bound; all assessments will be included. 
 
 
Table 2: Assessment Windows for Muscle Function Tests 
 
Analysis Visit 
Window 
Baseline 
Value at the visit on or prior to the first dose of study drug 
Target day=1, window = [L0, H0] = [--,1] 
Week X 
X = 12*K, k=1, 2, …, 16 
Target day = 7 * X + 1 
Window = [LK, HK] = [HK-1+1, Target Day+12*7/2-1] 
Week 204 
[L17  = H16  +1=1387, **] 
 
** There will be no upper bound; all assessments will be included. 
 
 
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Table 3: Assessment Windows for Cardiac MRI 
 
Analysis Visit 
Window 
Baseline 
Value at the visit on or prior to the first dose of study drug 
Target day=1, window = [L0, H0] = [--,1] 
Week X 
X = 52*K, k=1, 2, 3 
Target day = 7 * X + 1 
Window = [LK, HK] = [HK-1+1, Target Day+52*7/2-1] 
Week 208 
[L4  = H3 +1= 1275, **] 
* There will be no upper bound; all assessments will be included. 
 
Table 4: Assessment Windows for Vital Signs 
 
Analysis Visit 
Window 
Baseline 
 Baseline are defined as the average of last Screening and 
Week 0 pre-infusion measurements. 
 Target day=1, window = [L0, H0] = [--,1] 
Week X 
X = 2*K, k=1, 2, 3, …, 105 
Target day = 7 * X + 1 
Window = [LK, HK] = [HK-1+1, Target Day+6] 
*The last visit window will not have an upper bound; all assessment will be included. 
 
Table 5: Assessment Windows for Labs Tests 
Analysis Visit 
Window 
Baseline 
 Value at the visit on or prior to the first dose of 
study drug 
 Target day=1, window = [L0, H0] = [--,1] 
Week X 
X = 24*K, k=1, 2, …, 8 
Target day = 7 * X + 1 
Window = [LK, HK] = [HK-1+1, Target Day+24*7/2-1] 
Week 210 
[L9  = H8 +1= 1408, **] 
 
* There will be no upper bound; all assessments will be included. 
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All scheduled and unscheduled assessments are included in the by-visit summary. If more than two 
assessments are available in the same window, the last assessment will be used in the by- visit 
summary. 
If any visit is missed, assessments should be performed as soon after the missed visit as feasible. 
Missed infusions will not be replaced. 
Pamrevlumab infusion is NOT to be administered at week 208 (EOT). 
 
 
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APPENDIX 2. SAMPLE SAS CODE FOR RCM ANALYSIS 
 
SAS code for this model, using the primary endpoint ppFVC as example, is provided below. 
/*Random Coefficient Model (RCM) to estimate the change at year 1, 2, 3 and 
4*/ 
/*avisityr is the actual number of years from Day 1, avisityr=4 will be 
the change from baseline at year 4 */ 
/* fvc0= baseline ppFVC, should be used for change in FVC */ 
/* &meanfvc0= the mean of the baseline ppFvc 
*/ 
 
proc mixed data = fvc_obs; 
class subjid; 
model chgfvc = avisityr fvc0/solution cl covb outp=pred_fvc cl; 
random intercept avisityr /subject=subjid type=CS; 
ESTIMATE 'Change from Baseline at Year 1' intercept 1 avisityr 1 fvc0 
&meanfvc0 / CL; 
ESTIMATE 'Change from Baseline at Year 2' intercept 1 avisityr 2 fvc0 
&meanfvc0 / CL; 
ESTIMATE 'Change from Baseline at Year 3' intercept 1 avisityr 3 fvc0 
&meanfvc0 / CL; 
ESTIMATE 'Change from Baseline at Year 4' intercept 1 avisityr 4 fvc0 
&meanfvc0 / CL; 
ods output SolutionF=mxparms CovB=mxcovb Estimates=chgfrbl; 
      run; 
 
 
Sample SAS code for comparison 079 OLE data (trt = 1) with CINRG (trt = 0). 
PROC MIXED DATA = final; 
 
  CLASS trt SUBJID ;   
 
  MODEL chg = trt|avisityr base/ SOLUTION DDFM=KR;  
 
  RANDOM intercept avisityr / SUBJECT =SUBJID TYPE=UN GROUP= trt; 
 
 
  LSMEANS trt/ at avisityr = 1 PDIFF CL; 
 
  LSMEANS trt/ at avisityr = 2 PDIFF CL; 
 
  LSMEANS trt/ at avisityr = 3 PDIFF CL; 
 
  LSMEANS trt/ at avisityr = 4 PDIFF CL; 
 
 
  ods output LSMeans=LSMeans_chg diffs=diffs_chg; 
RUN;  
 
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Statistical Analysis Plan 
Addendum 
TITLE PAGE 
PROTOCOL TITLE: 
A Trial of FG-3019, a Monoclonal Antibody to Connective 
Tissue Growth Factor, in Non-Ambulatory Subjects with 
Duchenne Muscular Dystrophy (DMD) 
PROTOCOL NUMBER: 
Protocol FGCL-3019-079 
STUDY SPONSOR: 
FibroGen, Inc. 
409 Illinois Street 
San Francisco, California 94158 USA 
STUDY DRUG: 
Pamrevlumab 
INDICATION: 
Duchenne Muscular Dystrophy (DMD) 
SAP VERSION 
Addendum v1.1 
RELEASE DATE 
August 08, 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 #: NCT02606136


FGCL-3019-079 
 
Statistical Analysis Plan Addendum 
 
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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: 
Signature 
Date 
Reviewer: 
Signature 
Date 
Signature 
Date 
Signature 
Date 
 
 
 
Signature 
Date 
 
 
 
Signature 
Date 
 
 
 
Signature 
Date 
 
 


FGCL-3019-079 
 
Statistical Analysis Plan Addendum 
 
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Page 3 of 8 
 
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. 


FGCL-3019-079 
 
Statistical Analysis Plan Addendum 
 
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1. 
INTRODUCTION 
Study FGCL-3019-079 has reached DBL and an interim CSR has been completed. There was an 
error in p-value reporting in the original SAP which requires an amendment to all related tables 
and figures. The update is provided in this SAP addendum.  
Furthermore, as ADA samples were analyzed after the interim CSR, the analysis and reporting of 
ADA will be included in this SAP. 
 


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2. 
UPDATE TO THE ORIGINAL SAP 
 
Reason for change:  
The original approved SAP (version 1.0, dated June 25, 2020) specified 2-sided p-values to be 
reported for confidence intervals. However, the SAS function PROBT specified in SAP version 
1.0 Appendix 1 and errata to the SAP returned a 1-sided p-value. The following amendments are 
made to correct related p-values. 
 
In SAP Appendix I (on page 24, box on the left side below): the δ (or delta) should be (m1-m2) 
and t-test statistics should be (m1-m2)/se. 
 
 
 
In Errata to SAP (on Page 38, right side box above), which was not signed off with any 
signatories, δ (or delta) and t-test statistics were corrected, however, the p-value was still 1-sided.  
 
To correct this 1-sided p-value issue, the following highlighted in yellow is the only update to 
the Errata to SAP, where the p-value is multiplied by 2 and clarified as “2-sided”. 
 (SAS function: p= 2*probt(t, df) to get the 2-sided p-value for the t-test. 
Please note that if delta <= 0, p-value=p; if delta>0, p-value=1-p). 
 
In addition, in section 4.6.6.2 of the original SAP, the sentence “the results for the PUL total 
score will be compared with the results from Ricotti, 2019” shall be removed, since different 
versions of PUL were used. 
Since all secondary endpoints are “Change from Baseline to Week 104”, the estimate of annual 
change for some secondary endpoints will not be reported due to data and/or analysis model 
limitations. 
 
 


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3. 
IMMUNOGENICITY ANALYSIS 
3.1. 
Immunogenicity Analysis Set (IGS) 
The Immunogenicity Analysis Set (IGS) contains all the ADA/NAb evaluable patients, who are 
in the SAF analysis set with at least one ADA/NAb sample (with reportable results) taken pre-
treatment (i.e., a baseline sample) and at least one ADA/NAb sample (with reportable result) 
taken post-treatment. 
Analysis of immunogenicity data will be based on IGS.  Analysis dataset and data listing will 
include all available Human Anti-Human Antibody (HAHA, ADA) samples. The following 
terms and definitions are implemented. 
3.2. 
Terms and Definitions 
3.2.1. 
Sample ADA Status: 
• Baseline ADA-positive sample: ADA is detected in the last sample before initiation 
of treatment. 
• Baseline ADA-negative sample: ADA is not detected in the last sample before 
initiation of treatment. 
• Treatment-emergent ADA-Positive: Meets the definition of treatment-induced or 
treatment-boosted ADA. After initiation of treatment,  
− Treatment-induced ADA-Positive: a post-treatment positive ADA is detected in 
a subject for whom pre-treatment ADA assessment is either negative or not 
assessable, or  
− Treatment-boosted ADA-Positive: pre-existing ADA was boosted to a higher-
level following study treatment, i.e. pre-treatment positive ADA titer was boosted 
by at least 2 dilution steps (4-fold) following study treatment. 
• ADA-negative sample: After initiation of treatment, ADA is not treatment-emergent 
ADA-positive. 
Next, using the sample ADA status, subject ADA status is defined. 
3.2.2. 
Subject ADA Status: 
• Baseline ADA-positive subject: A subject with baseline ADA-positive sample.  
• ADA-positive subject:  An evaluable subject with at least one treatment-emergent 
ADA sample at any time during the study. 
• Neutralizing-positive: At least one treatment-emergent ADA-positive sample with 
neutralizing antibodies detected (if available). 
• ADA-negative subject: An evaluable patient without a treatment-emergent ADA 
sample during the study. 
 


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3.3. 
Statistical Analysis for Characterization of ADA Immune Response 
3.3.1. 
Incidence of ADA 
• Percentage of treatment-emergent ADA patients for the defined study period, where 
the denominator is the number of ADA evaluable patients in the respective treatment 
arm and/or subgroup. 
• Number (%) of subjects will be reported for the following parameters based on 
evaluable subjects: 
− Baseline ADA-positive 
− ADA-positive (Treatment-induced, Treatment-boosted) 
− Neutralizing Positive (if available) 
− ADA-negative 
• ADA prevalence: Percentage of treatment-emergent ADA patients at any given 
timepoint, where the denominator is the number of ADA evaluable patients in the 
respective treatment arm and/or subgroup at that timepoint. 
• A listing of all ADA assessments will be provided.  
• Additionally, a separate listing of ADA assessments for all neutralizing antibody 
(NAb)-positive subjects will be provided (if available). 
3.3.2. 
ADA Titer Kinetics  
All ADA-positive subjects will be included in the analysis. 
• Summary statistics of subject-level ADA titers using the maximum titer value within 
an ADA positive subject will be presented for baseline ADA-negative subjects and 
baseline ADA positive subjects. The median, interquartile range, and range of the 
maximum titers will be reported. For ADA-positive subjects with baseline ADA-
positive samples, the median and interquartile range of the fold increase from 
baseline in titer (ratio of maximum post-baseline titer to baseline titer) will also be 
reported. Graphical presentation of the summary data may be provided using 
boxplots, as appropriate. 
• For sample-level ADA titers, boxplots of ADA titers at each assessment timepoint 
will be provided, as appropriate, to demonstrate whether the ADA levels tend to 
change over time during the treatment, along with ADA incidence at each assessment 
timepoint. 
• Spider plots may be considered to show the trend of ADA titer over time for subjects 
with >/= 5 ADA results by splitting subjects into multiple spider plots (e.g., ≈ ≤10 
per plot, approximately. 
 


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3.4. 
Clinical Implication of ADA Immune Response 
3.4.1. 
Safety 
• Effect of ADA response on safety will be explored by examining the frequency and 
type of AEs of interest, including (1) Total TEAEs, (2) Drug Hypersensitivity, and (3) 
Infusion Reactions. For each category of AEs, summary tables for incidence will be 
provided for each of the preferred terms and overall within a category by ADA status, 
if the number of ADA-positive subjects is of sufficient size (e.g., at least ≈10 
subjects). Otherwise, individual subject’s safety profile will be examined and 
described based on a listing. 
• Listings of AEs will be provided. These listings will also indicate the study day and 
study period of the positive responses. 
3.4.2. 
Efficacy 
• The primary efficacy endpoint will be presented by ADA status.   
• Efficacy listings for all positive subjects (relative to baseline) will be provided. These 
listings will also indicate the study day and study period of the positive responses.