A NATURAL HISTORY STUDY IN CHINESE MALE PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY
Phase: NA
Conditions: Duchenne Muscular Dystrophy
Sponsor: Pfizer

C3391004 
Final Protocol Amendment 2, 16 Jun 2022 
PFIZER CONFIDENTIAL 
Page 1 
 
 
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otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
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unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer must be promptly 
notified. 
 
 
 
 
 
 
A NATURAL HISTORY STUDY IN CHINESE MALE PATIENTS WITH 
DUCHENNE MUSCULAR DYSTROPHY 
 
 
 
 
 
 
Therapeutic Area (TA): 
Rare Diseases 
Protocol Number: 
C3391004 
 
 
 
 

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Final Protocol Amendment 2, 16 Jun 2022 
PFIZER CONFIDENTIAL 
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Document History 
 
Document 
Version Date 
Amendment 2 
16 Jun 2022 
Amendment 1 
14-Sep-2020 
Original protocol 
15 May 2018 
 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs and any global protocol administrative 
change letter(s). 
Protocol Amendment Summary of Changes Table 
Amendment 2 (16 Jun 2022) 
Overall Rationale for the Amendment: Modify the study endpoints/objective without 
any change to the data that have been collected: The assessment of some endpoints in 
previous version of protocol are not quite appropriate, some of them may not reflect the 
disease progress and disease characteristic in an accurate manner. Amendment 2 is to make 
the endpoints reflect the disease progression and disease characteristic. 
 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
Section 2. Study 
Changed the primary 
To appropriately include 
Substantial 
objective and 
endpoints for time to 
participants in the 
endpoints 
run/walk 10 meters and analysis who are not able 
time to rise from floor 
to perform the activity 
to 10-meter run/walk 
and can be assigned a 
velocity and rise from 
value of zero velocity 
floor velocity (supine 
to stand), respectively, 
and moved them down 
to the third primary 
endpoint. 
Modified the wording 
of the assessment 
timepoints. 
Changed the primary 
Using %pFEV1 rather 
Substantial 
endpoint Forced 
than absolute FEV1 
Expiratory Volume in 
allows for continuous 
one Second (FEV1) to 
assessment across a 
percent predicted 
broad range of ages in 
Forced Expiratory 
which growth impacts 
the absolute FEV1 and 

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Section # and 
Name 
Description of 
Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
Volume in one Second 
(%pFEV1) 
will aid contextualizing 
the findings with other 
studies. 
Changed the secondary 
objective of quality of 
life from study the 
relationship between 
disease characteristics 
and quality of life to 
characterize the quality 
of life in Chinese 
DMD patients. 
Characterize the quality 
of life is usually the 
primary objective of 
QoL assessment. 
Substantial 
Removed the 
secondary objective of 
identify disease 
characteristics that 
could predict disease 
progression and the 
endpoints under this 
objective. 
To measure disease 
progression with 
descriptive summary of 
YES/No is less 
meaningful to be an 
endpoint; the objective 
could be considered in 
PMAP modeling which 
is also one part of the 
study. 
Substantial 
Modified the 
secondary endpoint of 
mutation types from 
large deletion, large 
duplication, small 
insertion/deletion, and 
point mutation to exon 
deletion, exon 
duplication, point 
mutation, small 
deletion, small 
insertion, and others. 
This is to make it align 
with the data collected in 
CRF. 
Substantial 
Changed the secondary 
endpoint of proportion 
of subjects with 
mutations involving 
key high frequency 
mutation sites to the 
proportion of each 
• 
To summarize the 
proportion of each 
affected exons by 
mutation types is to 
characterize Chinese 
population’s 
mutation, it is the 
Substantial 

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Section # and 
Name 
Description of 
Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
affected exons by 
mutation types, and the 
proportion of subjects 
with any mutation 
affecting any exon 
between exon 9 and 
exon 13, inclusive, or a 
deletion that affects 
both exon 29 and exon 
30. 
process ahead of 
identifying the high 
frequency mutation 
sites. 
• 
Population with any 
mutation affecting 
any exon between 
exon 9 and exon 13, 
inclusive, or a 
deletion that affects 
both exon 29 and 
exon 30, were at 
high risk of 
receiving gene 
therapy. 
Section 9.2 
Efficacy analysis 
Updated endpoints 
assessment according 
to the changes on 
objective and 
endpoints. 
To reflect the 
changes on 
endpoints. 
Substantial 
Section 2. Study 
objective and 
endpoints 
Clarified the primary 
endpoint assessments 
on time to life-altering 
clinical milestones are: 
age at failure to walk, 
age at failure to stand 
and age at failure to 
self-feed. 
Age at failure to 
walk/stand/self-feed 
reflects the disease 
course accurately. 
Nonsubstantial 
Clarified the primary 
endpoint of NSAA 
assessment is NSAA 
total score for 
ambulatory children 
aged ≥ 3 years and the 
PUL assessment is for 
total score and moved 
them up to the second 
primary endpoint. 
Modified the wording 
of the assessment 
timepoints. 
To make the assessment 
clear and accurate. 
Nonsubstantial 

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Section # and 
Name 
Description of 
Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
Clarified the primary 
endpoint assessment 
for strength of muscle 
is for the subjects aged 
≥ 5 years and modified 
the wording of 
assessment timepoints. 
To make the assessment 
clear and accurate. 
Nonsubstantial 
Modified the wording 
of primary endpoint 
assessment timepoints 
for ROM. 
To make the assessment 
clear and accurate. 
Nonsubstantial 
Clarified the secondary 
objective of assess the 
health care utilization 
to characterize the 
health care utilization. 
To make the description 
accurate. 
Nonsubstantial 
Moved the EQ-5D-Y 
and EQ-5D-3L up to 
the right criteria of 
quality-of-life 
endpoints from health 
care utilization 
endpoints. 
To make the description 
accurate. 
Nonsubstantial 
Clarified the secondary 
endpoints assessments 
for EQ-5D-Y, EQ-5D- 
3L, HRU and 
WPAI:CG. 
To make the assessments 
clear and accurate. 
Nonsubstantial 
Section 4.1 
Inclusion Criteria 
Clarified the definition 
of “stable GC 
(glucocorticoid) 
regimen” and the 
overall requirement on 
GC background 
treatment. 
To make the statement 
more detailed and 
accurate, aligned with 
global studies and all 
previous eligible 
activities in this study to 
comply with this 
definition. This is not a 
change to this criteria, it 
is a clarification. 
Nonsubstantial 
Section 6. Study 
procedures 
Modified the 
description on 
assessment for 
ambulatory and non- 
ambulatory in Section 
To avoid 
misunderstanding for the 
required assessments 
Nonsubstantial 

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Section # and 
Name 
Description of 
Change 
Brief Rationale 
Substantial or 
Nonsubstantial 
6 (including section 
6.1, 6.2 and 6.3). 
Section 7.4 
12-Lead 
Electrocardiograms 
Removed the ECG 
variables list and stated 
the investigator should 
review ECG and assess 
the clinical 
significance of ECG 
abnormalities . 
• 
ECG is for safety 
monitoring follows 
local clinical 
practice and the 
ECG variables will 
not be analyzed. 
• 
There is no impact 
on investigators’ 
judgement on 
patients’ safety. 
Nonsubstantial 
Section 7.5 
Removed total 
neutrophils (Abs) and 
allowed to collect 
either absolute or 
percentage for 
neutrophils, 
Eosinophils, 
Monocytes, Basophils, 
Lymphocytes. 
To avoid duplicate data 
collection. In lab library, 
total neutrophils (Abs) is 
same as Absolute 
neutrophils. 
Nonsubstantial 
Appendix1 to 5. 
Removed 
questionnaires from 
appendix 1 to 5 and to 
provide in independent 
documents without any 
change to the version 
and contents. 
The questionnaires are 
copyrighted and were 
removed from protocol 
to avoid any issues when 
the protocol is publicly 
disclosed. 
Nonsubstantial 
Document history 
Moved amendment 1 
information to 
Appendix 1 Protocol 
amendment history 
To meet the requirement 
in new protocol 
template. 
Nonsubstantial 
Throughout the 
protocol 
Corrected 
typographical errors 
where necessary. 
NA 
Nonsubstantial 

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TABLE OF CONTENTS 
APPENDICES ............................................................................................................................ 9 
SCHEDULE OF ACTIVITIES ................................................................................................ 10 
1. INTRODUCTION AND RATIONALE .............................................................................. 13 
2. STUDY OBJECTIVES AND ENDPOINTS ....................................................................... 14 
3. STUDY DESIGN ................................................................................................................. 15 
4. SUBJECT ELIGIBILITY CRITERIA ................................................................................. 16 
4.1. Inclusion Criteria ..................................................................................................... 16 
4.2. Exclusion Criteria .................................................................................................... 17 
4.3. Caregiver(s) ............................................................................................................. 17 
4.4. Sponsor’s Qualified Medical Personnel ................................................................... 18 
5. STUDY TREATMENTS ..................................................................................................... 18 
6. STUDY PROCEDURES ...................................................................................................... 19 
6.1. Visit 1/Baseline ........................................................................................................ 19 
6.2. Visits 2 and 4 (Months 6 and 18) ............................................................................. 21 
6.3. Visits 3, 5, and 6 (Months 12, 24, and 30) ............................................................... 22 
6.4. Participant Discontinuation/Withdrawal From the Study ....................................... 23 
6.4.1. Withdrawal of Consent: .............................................................................. 24 
6.5. Lost to Follow-up .................................................................................................... 24 
7. ASSESSMENTS .................................................................................................................. 24 
7.1. Physical Examinations ............................................................................................. 25 
7.2. Vital Signs ............................................................................................................... 25 
7.3. Anthropometrics ...................................................................................................... 25 
7.4. 12-Lead Electrocardiograms .................................................................................... 25 
7.5. Clinical Laboratory .................................................................................................. 25 
7.6. Functional Assessments ........................................................................................... 26 
7.6.1. Pulmonary Function Assessments ............................................................... 27 
7.6.2. Motor Functional Assessments ................................................................... 27 
7.6.2.1. Northstar Ambulatory Assessment ............................................ 27 
7.6.2.2. Range of Motion ........................................................................ 27 
7.6.2.3. Strength Assessment .................................................................. 28 
7.6.2.4. Performance of Upper Limb 2.0 ................................................ 28 
7.6.3. Echocardiogram .......................................................................................... 28 

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7.6.4. Cognitive Function Assessment .................................................................. 28 
7.7. Patient Reported Outcomes (PROs) ........................................................................ 29 
7.7.1. EuroQoL 5 Dimension (EQ-5D-3L/EQ-5D-Y) .......................................... 29 
7.7.2. Healthcare Resource Utilization Questionnaire .......................................... 29 
7.7.3. Work Productivity and Activity Impairment Questionnaire adapted 
for Caregiving .................................................................................................. 29 
7.7.4. Pediatric Outcomes Data Collection Instrument ......................................... 30 
7.8. Rater Qualifications ................................................................................................. 30 
8. SAFETY ............................................................................................................................... 31 
8.1. Adverse Events ........................................................................................................ 31 
8.2. Research Related Injury .......................................................................................... 31 
9. DATA ANALYSIS/STATISTICAL METHODS ............................................................... 32 
9.1. Sample Size Determination ..................................................................................... 32 
9.2. Efficacy Analysis ..................................................................................................... 32 
9.2.1. Analysis of the Primary Endpoint ............................................................... 32 
9.2.2. Analysis of Secondary Endpoints ............................................................... 33 
9.3. Safety Analysis ........................................................................................................ 33 
9.4. Interim Analysis ...................................................................................................... 33 
10. QUALITY CONTROL AND QUALITY ASSURANCE ................................................. 33 
11. DATA HANDLING AND RECORD KEEPING .............................................................. 34 
11.1. Case Report Forms/Data Collection Tools/Electronic Data Record ..................... 34 
11.2. Record Retention ................................................................................................... 35 
12. ETHICS .............................................................................................................................. 35 
12.1. Institutional Review Board/Ethics Committee ...................................................... 35 
12.2. Ethical Conduct of the Study ................................................................................. 35 
12.3. Subject Information and Consent .......................................................................... 36 
13. PUBLICATIONS BY INVESTIGATORS ........................................................................ 37 
14. REFERENCES ................................................................................................................... 39 
APPENDICES 
Appendix 1. Protocol Amendment History .............................................................................. 42 
Appendix 2. Abbreviations ....................................................................................................... 46 

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SCHEDULE OF ACTIVITIES 
The Schedule of Activities table provides an overview of the protocol visits and procedures. Refer to STUDY PROCEDURES and 
ASSESSMENTS sections of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the Schedule of Activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject. 
 
Visit Identifier 
Visit 1/ 
Baselinea 
Visit 2/ 
Month 6 
(Phone contact 
allowed for non- 
ambulatory boys) 
Visit 3/ 
Month 12 
Visit 4/ 
Month 18 
(Phone contact 
allowed for non- 
ambulatory boys) 
Visit 5/ 
Month 24b 
Visit 6/ 
Month 30/ End of Studyb 
(Phone contact allowed for 
non-ambulatory boys) 
Visit Window 
±4 weeks 
±4 weeks 
±4 weeks 
±4 weeks 
±4 weeks 
Informed consent/Assentc 
X 
Inclusion/exclusion criteria 
X 
General/DMD medical history & 
family history 
X 
Mutation type of DMD 
X 
Prior medication used 
X 
Demographics 
X 
Age of life-altering events 
X 
X 
X 
X 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
Anthropometrics 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
X 
X 
X 
X 
Pulmonary Function Assessmente 
FVC and FEV1 
X 
X 
X 
X 
MIP/MEP 
X 
X 
X 
X 
Peak cough flow 
X 
X 
X 
X 
Motor Function Assessmentf 
NSAA 
X 
X 
X 
X 
X 
X 
Passive range of motiong 
X 
X 
X 
X 
X 
X 
Myometryh 
X 
X 
X 
X 
X 
X 
PUL 2.0i 
X 
X 
X 
X 
X 
X 
Echocardiogram 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
WISCj 
X 
X 

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Visit Identifier 
Visit 1/ 
Baselinea 
Visit 2/ 
Month 6 
(Phone contact 
allowed for non- 
ambulatory boys) 
Visit 3/ 
Month 12 
Visit 4/ 
Month 18 
(Phone contact 
allowed for non- 
ambulatory boys) 
Visit 5/ 
Month 24b 
Visit 6/ 
Month 30/ End of Studyb 
(Phone contact allowed for 
non-ambulatory boys) 
Visit Window 
±4 weeks 
±4 weeks 
±4 weeks 
±4 weeks 
±4 weeks 
Subject and Caregiver Outcome Measures 
EQ-5D-3L/EQ-5D-Yk 
X 
X 
X 
X 
HRU questionnaire 
X 
X 
X 
X 
WPAI:CG 
X 
X 
X 
X 
PODCI 
X 
X 
X 
X 
X 
X 
Laboratory 
Hematology 
X 
X 
X 
X 
X 
X 
Blood chemistry 
X 
X 
X 
X 
X 
X 
Concomitant Treatment(s) 
X 
→ 
→ 
→ 
X 
AE and research related injury 
monitoring 
X 
→ 
→ 
→ 
→ 
X 
Abbreviations: →= ongoing/continuous event; CK = Creatine Kinase; DMD = Duchenne Muscular Dystrophy; ECG = Electrocardiogram; 
EQ-5D-3L = EuroQoL 5 Dimensions 3 Levels; EQ-5D-Y = EuroQoL 5 Dimensions - Youth; FEV1 = Forced Expiratory Volume in One Second; 
FVC = Forced Vital Capacity; HRU = Healthcare Resource Utilization questionnaire; NSAA = North-Star Ambulatory Assessment; MEP = Maximum 
Expiratory Pressure; MIP = Maximum Inspiratory Pressure; PODCI = Pediatric Outcomes Data Collection Instrument; PUL 2.0 = Performance of Upper Limb 
2.0; WISC = Wechsler Intelligence Scale for Children; WPAI:CG = Work Productivity and Activity Impairment Questionnaire adapted for Caregiving. 
a. 
The day on which Baseline is conducted will be considered as Day 1. 
b. The study will complete 24 months after the last subject is enrolled such that all subjects have data through at least 24 months. All subjects will remain 
enrolled until the study completion date, such that some will have data collected after Month 24. Subjects who complete Visit 5/Month 24 at least 6 months 
prior to study completion, will be asked to complete an additional visit at Month 30. For any individual subject, the last study visit prior to study 
completion will be considered as the end of study (EoS) visit. 
c. 
Informed consent must be provided by the subject’s caregiver (parent or legal guardian) for subjects aged <18 years. Subjects age ≥6 years and <18 years 
are required to provide signed assent. For those who are learning to read or who are illiterate, the assent form must be read to them and verbal assent 
obtained and documented on the assent form. 
d. The medication history includes prior use of glucocorticosteroids (GC) since the initiation of GC treatment and all other medication used in one year prior 
to signing consent form. 
e. 
The pulmonary function assessments will be performed in subjects age ≥6 years. 
f. 
Should subjects become non-ambulatory during the study, the NSAA will not be collected after that time. In addition, young subjects may not be able to 
perform the NSAA or myometry. But once a subject is deemed capable of performing a measure, it will be performed at all subsequent visits. Please find 
in Section 7 for details about the age above which the assessment is required to start. 

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Visit Identifier 
Visit 1/ 
Baselinea 
Visit 2/ 
Month 6 
(Phone contact 
allowed for non- 
ambulatory boys) 
Visit 3/ 
Month 12 
Visit 4/ 
Month 18 
(Phone contact 
allowed for non- 
ambulatory boys) 
Visit 5/ 
Month 24b 
Visit 6/ 
Month 30/ End of Studyb 
(Phone contact allowed for 
non-ambulatory boys) 
Visit Window 
±4 weeks 
±4 weeks 
±4 weeks 
±4 weeks 
±4 weeks 
g. Range of motion will be evaluated by using goniometry to record any occurrences of elbow and ankle contractures. 
h. Myometry will be used to evaluate the muscle strength of the following muscle groups: knee extension, elbow flexion, elbow extension and shoulder 
abduction. 
i. 
PUL 2.0 will be assessed in subjects ≥10 years. 
j. 
The WISC scale will be performed in subjects age ≥6 years to ≤16 years old who are still ambulatory at time measurement. 
k. EQ-5D-3L will be completed by subjects who are aged ≥16 years, EQ-5D-Y will be completed by subjects who are aged <16 years and able to read and 
complete the questionnaire. 

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1. INTRODUCTION AND RATIONALE 
Duchenne Muscular Dystrophy (DMD), the most common type of muscular dystrophy, is an 
X-linked recessive genetic disorder caused by mutations in the gene for dystrophin that result 
in progressive loss of muscle fibers.1 The disabling and life-threatening disease is 
characterized by weakness, with stereotypic functional consequences affecting mobility, 
progressive musculoskeletal deformities, upper limb impairment, impaired airway clearance 
and ventilation, cardiomyopathy, and premature death.2 While the epidemiology data from 
large scale studies is limited in the Chinese population, the incidence of DMD has been 
estimated at 1 in 3,500 – 5,000 or 2 - 2.9 per 10,000 male births in western countries and the 
existing literature supports the conclusion that incidence does not vary significantly by racial, 
ethnic, or geographical origins.3,4 
There are several reasons to obtain natural history from a current cohort of patients. The 
overall natural history of DMD has changed significantly in over the past 20-30 years. With 
the introduction glucocorticoid (GC) therapy systematic implementation of the standards of 
care, loss of ambulation is occurring several years later.5-7 It is now recognized that the 
course of DMD can be influenced by the age at which GC therapy is started and by the GC 
regimen.8,9 Aggressive respiratory care and the use of mechanical ventilation has caused a 
significant increase in life expectancy.10,11 In addition, mutation-specific therapeutic 
approaches have generated the need for understanding the natural progression of the targeted 
genotype subgroups, especially if it differs from the overall DMD population. It is 
recognized, for example, that some patients with mutations skippable by exon 44 or 45 may 
present a phenotype intermediate between DMD and Becker Muscular Dystrophy (BMD), 
due to an elevated number of revertant fibres and residual dystrophin expression.12,13 
In addition, although several recent studies provide insight into the natural history of DMD, 
they are primarily focused on the progression of lower extremity motor function, and 
particularly on ambulation.5,18 Fewer have been published characterizing the progression of 
upper extremity weakness or pulmonary disease.19,20 Although there are cross-sectional 
evaluations of the disease state in younger boys (eg, <6 years old), there are no published 
accounts of longitudinal studies in this population. There are ongoing efforts by multiple 
groups to identify predictors of disease progression, but very few of these have been 
published.21 These gaps in our understanding of the natural history are impediments to 
adequately planning interventional clinical trials for the entire DMD population. 
The natural history of DMD remains unclear in the current Chinese patient population as 
limited data is available. In China, although GC therapy has been recommended by the 
guideline for DMD patients, the proportion of patients who receive it remained as low as 
26.29%.14 In the same study, it was also observed that <50% and <20% of the patients 
received cardiac and pulmonary function monitoring, respectively. A few studies have 
observed that the genotypes of DMD in Chinese patients are similar to those observed in 
western countries.14-16 
This natural history study will not only offer a description of the progression of the condition 
according to current standards of care in Chinese population, it can also meaningfully inform 

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the design of clinical trials in terms of endpoints and patient populations that meet the 
specific needs of Pfizer programs: 
• The study design and proposed analyses can align with the mechanism of action of 
specific compounds in development and with anticipated studies included in the 
Clinical Development Plans; 
• Multiple analyses can be performed by altering specific variables so as to explore 
future trial designs and to conduct the relevant power analyses; 
• Analyses can be conducted on the same populations and endpoints as utilized in 
interventional studies with results included in regulatory documents to provide 
context for the findings of the interventional trial. 
2. STUDY OBJECTIVES AND ENDPOINTS 
 
Primary Objective: 
Primary Endpoints: 
To characterize the natural history of Chinese DMD 
patients. 
• 
Time to life-altering clinical milestones due to DMD 
disease progression, including: 
• 
Age at Failure to walk; 
• 
Age at Failure to stand; 
• 
Age at Failure to self-feed. 
• 
Change from Baseline at each post-baseline visit in 
clinical evaluator (CE) determined scales: 
• 
Northstar Ambulatory Assessment (NSAA) 
total score (ambulatory children aged ≥3 years); 
• 
Performance of Upper limb 2.0 (PUL 2.0) total 
score (subjects aged ≥10 years). 
• 
Change from Baseline at each post-baseline visit in 
timed motor functions (Ambulatory subjects) , 
including: 
• 
Rise from floor velocity (supine to stand);* 
• 
10 meter walk/run velocity;* 
• 
Change from Baseline at each post-baseline visit in 
strength of muscle groups (subjects aged ≥ 5 years): 
• 
Knee extension; 
• 
Elbow flexion; 
• 
Elbow extension; 
• 
Shoulder abduction. 
• 
Change from Baseline at each post-baseline visit in 
range of motion (ROM) at bilateral ankles and 
elbows. 
• 
Change from Baseline in pulmonary function tests 
(subjects aged ≥ 6 years) at Months 12, 24, and 30, 
including: 
• 
Percent predicted Forced Vital Capacity 
(%pFVC); 
• 
Percent predicted Forced Expiratory Volume in 
one Second (%pFEV1); 
• 
Maximum Inspiratory Pressure (MIP); 
• 
Maximum Expiratory Pressure (MEP); 
• 
Peak cough flow. 

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• 
Change from Baseline in cardiac functions at 
Months 12, 24, and 30, including: 
• 
Left ventricular ejection fraction (LVEF). 
• 
Change from Baseline in Wechsler Intelligence 
Scale for Children (WISC) score at Month 24 
(ambulatory subjects aged ≥6 years to ≤16 years). 
Secondary Objectives: 
Secondary Endpoints: 
To characterize the prevalence of mutation types in 
Chinese DMD patients. 
• 
DMD Mutation Type Endpoints: 
• 
Proportion of subjects with mutation of exon 
deletion, exon duplication, point mutation, 
small insertion, small deletion, and others. 
• 
The proportion of each affected exon by 
mutation types. 
• 
The proportion of subjects with any mutation 
affecting any exon between exon 9 and exon 
13, inclusive, or a deletion that affects both 
exon 29 and exon 30. 
To characterize the quality of life in Chinese DMD 
patients. 
• 
Quality of life endpoints: 
• 
Change from Baseline in Pediatric Outcomes 
Data Collection Instrument (PODCI) Global 
Functioning Scale and each subscale scores at 
each post-baseline visit. 
• 
Response to each of the 5 dimensions of 
EuroQoL 5 Dimension 3 Level (EQ-5D-3L)/ 
EuroQoL 5 Dimension Youth (EQ-5D-Y) and 
change from baseline in EQ-5D-3L/EQ-5D-Y 
（including VAS scores and index scores）at 
Months 12, 24, and 30. 
To characterize the health care utilization in Chinese 
DMD patients. 
• 
Health care utilization endpoints: 
• 
Change from Baseline in Healthcare Resource 
Utilization (HRU) survey responses (including 
the number of office visits, out-of-pocket 
expenses, visits to the emergency room, and 
number of nights stayed in the hospital) at 
Months 12, 24, and 30. 
• 
Change from Baseline in Work Productivity 
and Activity Impairment Questionnaire adapted 
for Caregiving (WPAI:CG) questionnaire 
scores (including absenteeism, presenteeism, 
work productivity loss, and activity 
impairment) at Months 12, 24, and 30. 
Note: 
*The assessments rise from floor and walk/run 10 meters will be performed as part of NSAA assessment. 
 
 
3. STUDY DESIGN 
This is a multicenter, prospective, single cohort study designed to describe the natural history 
of DMD in Chinese male patients. The study is planned to be conducted in 6-8 sites in 

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China. A total of approximately 330 subjects will be enrolled with the target number of 
subjects in each group as below: 
• Group 1, Ambulatory subjects aged <6 years, approximately 100 subjects; 
• Group 2, Ambulatory subjects aged ≥6 years, approximately 180 subjects; 
• Group 3, Non-ambulatory subjects, approximately 50 subjects. 
Subjects will be enrolled in parallel for all age groups. Subjects who are too young to 
develop the ambulant ability will be considered ambulatory. Each subject will be observed 
for at least 24 months, ie, the study will be ended 24 months after the last subject is enrolled 
such that all subjects have data through at least 24 months. All subjects will remain enrolled 
until the study completion date, such that some will have data collected after Month 24. Data 
collected during the first visit will be considered the Baseline assessments. The subjects will 
subsequently be assessed at Months 6, 12, 18, and 24. Subjects, who complete 
Visit 5/Month 24 at least 6 months prior to study completion, will be asked to complete an 
additional visit at Month 30. The end of study (EoS) Visit will be the last completed visit at 
Month 24 or 30. For any individual subject, the last study visit prior to study completion will 
be considered the end of study visit. During visit at Months 24, it will be determined 
whether the subjects will be able to attend the visit at Month 30, based on the projected study 
completion date. 
No investigational drug is being studied or provided to subjects in this study. Subjects will 
be allowed to take medications prescribed by their physicians, which will constitute the 
standard of care (SOC). Subjects who are ≥ 4 years of age must be receiving GC for 
6 months with at least 3 months on stable dose prior to study entry. Subjects who are aged 
<4 years will be exempt from this requirement; those not taking GC will be eligible if the 
initiation of GC treatment in these subjects is considered inappropriate in the opinion of 
Investigators. There is no restriction regarding other therapies for DMD or for concomitant 
conditions. 
4. SUBJECT ELIGIBILITY CRITERIA 
This study can fulfill its objectives only if appropriate subjects are enrolled. The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol. 
4.1. Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the 
study: 
1. Chinese males of any age, diagnosed with DMD. Diagnosis must be confirmed in 
subject’s medical history and by genetic testing obtained during routine clinical care 
for diagnostic purposes as reported from an appropriate regulated laboratory using a 
clinically validated genetic test. Results must confirm the presence of a mutation in 
the dystrophin gene which is consistent with the diagnosis of DMD. 

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2. Evidence of a personally signed and dated informed consent and assent (where 
appropriate) document indicating that the subject and parent(s) have been informed of 
all pertinent aspects of the study. Subjects will be required to provide assent in 
compliance with local regulations and Institutional Review Board (IRB) 
requirements. 
3. For subjects ≥ 4 years old, they must be receiving GC for a minimum of 6 months 
including a stable regimen of GC for at least 3 months prior to signing informed 
consent. To be considered a stable regimen, there should be no significant change 
(change >0.2 mg/kg in daily dose) in dosage or dose regimen other than that related to 
body weight change for at least 3 months immediately prior to signing the informed 
consent. Subjects who are aged <4 years will be exempt from this requirement; those 
not taking GC will be eligible if the initiation of GC treatment in these subjects is 
considered inappropriate in the opinion of Investigators. 
4. Subjects who are willing and able to comply with scheduled visits, laboratory tests, 
and other study procedures. 
4.2. Exclusion Criteria 
Subjects with any of the following characteristics/conditions will not be included in the 
study: 
1. Any injury which may impact functional testing. Previous injuries must be fully 
healed prior to consenting. Prior lower limb fractures must be fully healed and at 
least 3 months from injury date. 
2. Presence or history of other musculoskeletal or neurologic disease or somatic 
disorders not related to DMD including pulmonary, cardiac, and cognitive diseases. 
3. Subjects ≥4 years old who have not completed the varicella vaccination. 
4. Subjects who are investigator site staff members directly involved in the conduct of 
the study and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are Pfizer employees, including their family members, 
directly involved in the conduct of the study. 
5. Participation in other studies involving investigational drug(s) within 90 days prior to 
study entry and/or during study participation. 
4.3. Caregiver(s) 
The parent(s) or legal guardian(s) of the subject aged <18 years will actively participate as 
caregiver in this study. Caregivers of adult subjects are those who take care of the subjects 
while not paid for their caregiving. The caregiver(s) will not only provide informed consent, 
but will also actively participate in the study, including attendance at study visits, wellness 
follow-up calls and completion of patient-reported questionnaires on behalf of the subject as 
well as themselves. The caregiver(s) will also communicate observed safety information to 
the investigator or designee as appropriate. 

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A subject’s caregiver(s) must meet all of the following criteria for the subject to be eligible 
for enrollment in the study: 
1. Aged ≥18 years of age and has demonstrated responsibility as a legal caregiver(s) 
through monitoring the subject and reporting any observed adverse events (AEs); 
2. Willingness and ability to provide written informed consent on behalf of the subject; 
3. Ability to accompany the subject to the clinic visits; 
4. Ability to follow instructions. 
4.4. Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor’s appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study documentation. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum: 1) protocol identifiers, 2) subject study numbers, 3) contact information for 
the investigator site, and 4) contact details in the event that the investigator site staff cannot 
be reached to provide advice on a medical question or problem originating from another 
healthcare professional not involved in the subject’s participation in the study. The contact 
number can also be used by investigator staff if they are seeking advice on medical questions 
or problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available. It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study. The contact number is not intended for use by the subject directly, 
and if a subject calls that number, he or she will be directed back to the investigator site. 
5. STUDY TREATMENTS 
No investigational medicine will be given to subjects in this study. 
Subjects who are being treated with GC are encouraged to continue the treatment during the 
study. The GC should be given according to the SOC, either daily or intermittently 
(eg, prednisolone 10 days on and then 10 days off or alternate days). Dose reduction will be 
allowed if the subject experiences intolerable adverse side-effects or becomes 
non-ambulatory during the study. 
For those subjects who are GC-naïve at study entry, the timing of initiation of GC therapy 
should be decided individually based on functional state, age, and pre-existing risk factors for 
adverse side-effects. In all cases, the varicella vaccination should be completed before GC 
treatment is started. The completion of the varicella immunity must be documented on the 
corresponding case report form (CRF). 

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Other concomitant medicines that are prescribed for treatment of DMD, physical therapy, 
and rehabilitation and/or psychosocial interventions will be prescribed by the treating 
physician as needed. 
There is no limitation to therapies for concomitant conditions such as pulmonary infection 
and cardiac failure. Such concomitant therapies, including the hospitalizations, surgeries, 
and new or changed devices will be reported on the CRF. 
6. STUDY PROCEDURES 
Every attempt should be made to schedule the visits on the day specified in the Schedule of 
Activities. In order to provide optimal testing conditions and consistency in endpoint 
measurements, when the functional assessments and clinical laboratory assessments are 
scheduled to be completed at the same visit, these may be completed on two consecutive 
days within the visit window. Every effort will be made to have the functional assessments 
performed at approximately the same time of day for all visits. 
The first visit will be considered the Baseline visit. During this visit, screening will be 
conducted first, and if a subject is enrolled, the Baseline assessments will then be performed 
on that same visit. The visit window for all follow-up visits is ±4 weeks. Functional 
assessments should be routinely collected when the subject is rested and well-fed. 
Should subjects become non-ambulatory during the study, the NSAA will not continue to be 
collected. In addition, young subjects may not be able to perform the NSAA or myometry. 
But once a subject is deemed capable of performing a measure, it will be performed at all 
subsequent visits. Please find in Section 7 for details about the age above which the 
assessment is required to start. The motor and pulmonary functional assessments will not be 
performed if the subjects are too young to reliably perform the assessments, at the discretion 
of Investigators. For these subjects, the functional assessments will start to be performed 
when they develop the required capacity in the judgement of Investigators. 
6.1. Visit 1/Baseline 
During the Baseline visit, subjects will be assessed for study eligibility through review of 
genetic testing results, medical history, and medication history. The day on which Baseline 
is conducted will be considered as Day 1. 
• The report of genetic testing for the diagnosis of DMD as obtained from an 
appropriate regulated laboratory using a clinically validated genetic test will be 
reviewed. Results must confirm the presence of a mutation in the dystrophin gene 
which is consistent with the diagnosis of DMD. The mutation type will be recorded 
in the CRF as exon deletion, exon duplication, point mutation, small insertion, small 
deletion, and others. 
• A comprehensive medical history and medication history review will be performed 
for each subject for eligibility confirmation. This will include review of any 
significant past medical history and concurrent illnesses that are specified in the 
exclusion criteria. Complete medication history will include all prescription and 

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nonprescription drugs, and dietary and herbal supplements taken within 1 year prior 
to signing informed consent. The history of GC treatment will include dosage and 
dose regimens from the initiation of the treatment, if available. 
• Written informed consent will be obtained from subjects who are ≥18 years old prior 
to initiation of any screening activities. For subjects who are younger than 18 years 
of age, the caregiver(s) (parent or legal guardian) must sign the informed consent. 
Subjects aged ≥6 years and <18 years are required to provide signed assent, while for 
those who are learning to read or who are illiterate, the assent form will be read to 
them and then verbal assent will be obtained and documented on the assent form. 
Assent is not required for subjects who are aged <6 years. 
Once the subject is confirmed as eligible and consent/assent has been obtained, the 
following Baseline assessments will be performed. 
This initial visit might be conducted within 2 consecutive days at some investigator sites. 
The motor function assessments should be conducted on a single visit day whenever possible. 
• Family history. 
• Age of life-altering events including failure to walk, failure to stand, and/or failure to 
self-feed will be collected. 
The status of “Non-ambulatory” will be recorded in this study when it meets the 
following definition: 1) full-time wheelchair use or being unable to complete daily 
activities (such as going to bathroom) by walking independently, based on reported 
performance at home by subject or caregiver AND 2) verification by trained CE with 
the inability to perform the 10-meter run/walk assessment. 
• Demographic information including date of birth, ethnicity, province of residence, 
and urban or rural area of residence. 
• Physical examination including spine deformity evaluation. 
• Vital signs including supine blood pressure, pulse rate, and respiratory rate. 
• Anthropometric measures: height, ulnar length, and weight. 
• Motor and pulmonary functional assessments: in the following order (omitting any 
that are not applicable based on subject’s age and the status of ambulant or not): 
• FVC, FEV1, MIP/MEP, peak cough flow; 
• NSAA; 
• ROM; 
• Muscle strength assessment by myometry; 

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• PUL. 
• Cardiac function assessments: 
• Echocardiogram. 
• 12-lead electrocardiograms (ECGs). 
• Wechsler Intelligence Scale for Children. 
• Subject and caregiver outcome measures: 
• PODCI; 
• EQ-5D-3L/EQ-5D-Y; 
• HRU questionnaire; 
• WPAI:CG questionnaire. 
• Blood samples for hematology and chemistry. 
• AE and research related injury monitoring. 
6.2. Visits 2 and 4 (Months 6 and 18) 
The visits should be completed within 2 consecutive days, all assessments should be 
conducted at approximately the same time of day. Phone contact is allowed for the subjects 
who are assessed as non-ambulatory at last visit or earlier. Those subjects who are 
ambulatory at last visit must visit the study site for assessments. 
• Physical examination including spine deformity evaluation. 
• Vital signs including supine blood pressure, pulse rate, and respiratory rate. 
• Anthropometric measures: height, ulnar length, and weight. 
• Motor and pulmonary functional assessments: in the following order (omitting any 
that are not required based on subject’s age and the status of ambulant or not): 
• NSAA; 
• ROM; 
• Strength assessment by myometry; 
• PUL. 

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• PODCI. 
• Blood samples for hematology and chemistry. 
• Interval occurrence of life-altering events including failure to walk, failure to stand, 
and/or failure to self-feed. 
• Concomitant treatment monitoring. 
• AE and research related injury monitoring. 
6.3. Visits 3, 5, and 6 (Months 12, 24, and 30) 
These visits may be conducted within 2 consecutive days, as determined by the site. All 
assessments should be conducted at approximately the same time of day. 
The date of EoS will have been determined before Visit 5/Month 24 for all subjects; 
therefore, the Investigator should make the determination at Visits 5 for each subject whether 
the study will be ended before the next visit. 
For Visit 6/Month 30, phone contact is allowed for the subjects who are assessed as 
non-ambulatory at Visit 5/Month 24 or earlier. Those subjects who are ambulatory at 
Visit 5/Month 24 must visit the study site for assessments. 
• Physical examination including spine deformity evaluation. 
• Vital signs including supine blood pressure, pulse rate, and respiratory rate. 
• Anthropometric measures: height, ulnar length, and weight. 
• Motor and pulmonary functional assessments: in the following order (omitting any 
that are not required based on subject’s age and the status of ambulant or not): 
• FVC, FEV1, MIP/MEP, peak cough flow; 
• NSAA; 
• ROM; 
• Strength assessment by myometry; 
• PUL. 
• Cardiac function assessments: 
• Echocardiogram. 
• 12-lead ECG. 

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• Wechsler Intelligence Scale for Children, only at Visit 5/Month 24. 
• Subject and caregiver outcome measures: 
• PODCI; 
• EQ-5D-3L/EQ-5D-Y; 
• HRU questionnaire; 
• WPAI:CG questionnaire. 
• Blood samples for hematology and chemistry. 
• Disease progression in life-altering events including failure to walk, failure to stand, 
and/or failure to self-feed. 
• Concomitant treatment monitoring. 
• AE and research related injury monitoring. 
6.4. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following: 
• Refused further follow-up; 
• Lost to follow-up; 
• Death; 
• Study terminated by sponsor. 
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. 
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent. 

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Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved. 
6.4.1. Withdrawal of Consent: 
Subjects who discontinue GC treatment will remain in the study and will continue to adhere 
to protocol-specified procedures. The only exception to this is when a subject specifically 
withdraws consent for any further contact with him or persons previously authorized by the 
subject to provide this information. Subjects or his legal guardian(s) should notify the 
investigator in writing of the decision to withdraw consent from future follow-up, whenever 
possible. The withdrawal of consent should be explained in detail in the medical records by 
the investigator, as to whether the withdrawal is from study procedures and/or study 
follow-up, and entered on the appropriate CRF page. In the event that vital status (whether 
the subject is alive or dead) is being assessed publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law. 
6.5. Lost to Follow-up 
All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject as noted above. If a 
subject does not return for a scheduled visit, every effort should be made to contact the 
subject. All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record. In any circumstance, every effort 
should be made to document subject outcome, if possible. The investigator should inquire 
about the reason for withdrawal, and request that the subject return for a final visit, if 
applicable. Lost to follow-up is defined by the inability to reach the subject after a minimum 
of 2 documented phone calls, faxes, or e-mails as well as lack of response by the subject to 
1 registered mail letter. All attempts should be documented in the subject’s medical records. 
If it is determined that the subject has died, the site will use locally permissible methods to 
obtain the date and cause of death. If the investigator’s use of a third-party representative to 
assist in the follow-up portion of the study has been included in the subject’s informed 
consent, then the investigator may use a sponsor-retained third-party representative to assist 
site staff with obtaining the subject’s contact information or other public vital status data 
necessary to complete the follow-up portion of the study. The site staff and representative 
will consult publicly available sources, such as public health registries and databases, in 
order to obtain updated contact information. If, after all attempts, the subject remains lost to 
follow-up, then the last-known-alive date as determined by the investigator should be 
reported and documented in the subject’s medical records. 
7. ASSESSMENTS 
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study. 

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7.1. Physical Examinations 
Physical examinations will be conducted by a physician. The physical examination will 
include head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, 
gastrointestinal, musculoskeletal, and neurological systems. 
7.2. Vital Signs 
Vital signs (supine blood pressure, pulse rate, and respiratory rate) will be measured at times 
specified in Schedule of Activities section of this protocol. 
Supine blood pressure will be measured with the subject’s arm supported at the level of the 
heart, and recorded to the nearest mm Hg after at least 5 minutes of rest. Whenever possible, 
the same arm (preferably the dominant arm) should be used throughout the study. 
Wherever possible, the same size blood pressure cuff, which has been properly sized and 
calibrated, will be used to measure blood pressure each time. The use of automated devices 
for measuring BP and pulse rate are acceptable, although, when done manually, pulse rate 
will be measured in the brachial/radial artery for at least 30 seconds. 
7.3. Anthropometrics 
Height and weight will be measured at times defined in the Schedule of Activities section of 
this protocol. 
If the subject is unable to stand independently for an appropriate standing height measure, the 
calculated height as derived from the ulnar measure will be used. The method developed by 
LM Gauld 200422 will be used for this estimation. The subject must be seated comfortably 
with the right arm positioned at his side and the elbow positioned at 90 degrees of flexion. 
The measured or calculated standing height will be recorded to the one-tenth of a centimeter 
on the worksheet. 
Body weight will also be measured by weight scale which is used in clinical practice in the 
study site. Calibration of the weight scale must be performed before the first measurement at 
each site. 
7.4. 12-Lead Electrocardiograms 
12-lead ECGs will be performed as described in Schedule of Activities. 
A 12–lead ECG should be recorded after subjects have been resting at least 5 minutes in the 
supine position in a quiet environment. ECG will be recorded and reviewed by the clinical 
site, and the clinical significance of ECG abnormalities will be assessed by the Investigator. 
7.5. Clinical Laboratory 
The following laboratory tests will be performed at times defined in the Schedule of 
Activities section of this protocol. Unscheduled clinical labs or repeating testing may be 
obtained at any time as deemed necessary per Investigators during the study. The blood tests 
for chemistry and hematology will be performed at the local laboratory at study site. 

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Chemistry 
Hematology 
Sodium 
Hemoglobin 
Potassium 
Hematocrit 
Calcium 
RBC count 
Chloride 
Platelet count 
Bicarbonate (Actional bicarbonate (HCO3-)) 
WBC count (and morphology as applicable) 
Glucose (non fasting) 
Neutrophils (Absolute or %) 
Blood Urea Nitrogen (BUN) or Urea (If BUN is not 
Eosinophils (Abs or %) 
available) 
Monocytes (Abs or %) 
Creatinine 
Basophils (Abs or %) 
Total and direct bilirubin 
Lymphocytes (Abs or %) 
Alkaline Phosphatase 
Total protein 
Albumin 
Serum phosphorus 
Uric acid 
Cystatin C 
25-OH-VD3 
Aspartate transaminase (AST) 
Alanine transaminase (ALT) 
Lactate dehydrogenase (LDH) 
High density lipoprotein (HDL) 
Low density lipoprotein (LDL) 
Creatine kinase (CK) 
Cardiac Troponin I or Cardiac Troponin T (If Cardiac 
Troponin I is not available) 
7.6. Functional Assessments 
Functional assessments will be obtained according to the Schedule of Activities. In order to 
provide optimal testing conditions and consistency in endpoint measurements, the functional 
assessments should be completed at approximately the same time of day, when the subject is 
rested and well-fed. The order for completing all testing will be detailed in a functional 
assessment manual. 
Should subjects become non-ambulatory during the study, the NSAA will not continue to be 
collected. The motor and pulmonary functional assessments will not be performed if the 
subjects are too young to reliably perform the assessments, at the discretion of Investigators 
and CEs. However, for these subjects, the functional assessments will start to be performed 
when they develop the required capacity in the judgement of Investigators. The age above 
which each assessment is required to start is specified below. 
All functional assessments will be conducted by a trained physiotherapist (or exercise 
physiologist). Throughout the study they will be referred to as CEs. Training and 
confirmation that the functional assessments are performed reliably will be provided by a 
vendor (master physiotherapist [MP]). Following the completion of training and reliability 
testing, a certificate will be provided which must be in place at each site prior to conducting 
any functional assessments. 
In order to assure ongoing quality of the CE abilities to perform functional assessments, 
videotaping will be used at pre-specified visits. Videos will be reviewed by the MPs to 
provide feedback to the CEs on the conduct of the method used to perform the functional 
assessment. Videos will not be used to provide scoring on subject’s functional assessment. 

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The videos will be stored at the site and retained per the record retention requirements 
described in Section Record Retention. 
The requirements for training and ongoing quality control will be described in the Functional 
Assessment manual. 
7.6.1. Pulmonary Function Assessments 
Pulmonary function testing will be completed to evaluate the maximal lung function using 
spirometry. The maneuvers tested include FVC, FEV1, MIP, MEP, and peak cough flow. 
The best (largest) FVC and FEV1 values will be used to calculate %pFVC and %p FEV1 
according to age, height, race, and gender23, %pFVC was recommended as an endpoint in 
DMD studies by experts in the DMD field.24 Using %pFVC and %p FEV1 rather than 
absolute FVC and FEV1 allows for continuous assessment across a broad range of ages in 
which growth impacts the absolute FVC and FEV1, and will aid contextualizing the findings 
with other studies. The pulmonary function assessments will be performed in subjects 
≥6 years old. 
Calibration of the spirometer must be performed before each assessment according to the 
system instructions. A difference in actual versus recorded volume of 3% or less will be 
acceptable. If more than one assessment is conducted on the same day, it is only required to 
calibrate the device once each day. 
The test environment must be set up prior to subject arrival and must be free of any and all 
distractions. The subject may take a practice test to become familiarized with the equipment. 
The test should be repeated at least three times making sure that the subject has recovered 
between attempts. The best (largest) of 3 attempts will be documented on the CRF. 
More details regarding calibration of the spirometer can be found in the Function Assessment 
manual. 
7.6.2. Motor Functional Assessments 
7.6.2.1. Northstar Ambulatory Assessment 
The NSAA is a 17-item test that grades performance of various functional skills using the 
following scale: 0 (unable to perform), 1 (completes independently but with modifications), 
or 2 (complete without compensation).25 The NSAA also includes 2 timed function tests: 
rise from floor and run 10 meters. The NSAA has been found to correlate with other 
functional outcomes in boys with DMD.26 The NSAA will be performed in ambulatory 
children ≥3 years old. 
7.6.2.2. Range of Motion 
Range of motion will be evaluated by using goniometry to record any occurrences of elbow 
and ankle contractures. 

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7.6.2.3. Strength Assessment 
Muscle strength will be quantified by means of a handheld myometry. The following muscle 
groups will be evaluated: knee extension, elbow flexion, elbow extension and shoulder 
abduction. Muscle strength will be assessed by myometry in subjects ≥ 5 years old. Those 
who are younger than 5 years may also be assessed if they are able to provide reliable 
measurements, as determined at the discretion of the Investigators. 
7.6.2.4. Performance of Upper Limb 2.0 
The PUL 2.0 scale has been devised to assess motor performance of the upper limb for 
individuals with dystrophinopathies (Becker and Duchenne muscular dystrophy).27 The 
purpose of an upper limb scale for use in dystrophinopathy is to assess change that occurs in 
motor performance of the upper limb overtime from when a boy is still ambulant to the time 
he loses all arm function when non-ambulant. Motor performance will be impacted by 
muscle strength, contractures and maturational development (puberty) and the scale aims to 
incorporate performance of shoulder, elbow, wrist and hand function. The PUL will be 
administered in subjects ≥10 years old. 
7.6.3. Echocardiogram 
Echocardiograms should be collected at times specified in the Schedule of Activities section 
of this protocol. Echocardiogram should be performed using a 2-D imaging collection 
method. It will be performed in subjects ≥6 years old. 
Echocardiogram will be read locally at each site. A qualified individual at the investigator 
site will evaluate the echocardiogram for left atrial diameter, left ventricular mass index, left 
ventricular end diastolic diameter, left ventricular end systolic diameter, LVEF, shortening 
fraction, left ventricular posterior wall thickness, tricuspid valvular regurgitation presence 
and pericardial effusion. 
7.6.4. Cognitive Function Assessment 
The WISC will be used to assess the intelligence of subjects at times specified in the 
Schedule of Activities section of the protocol. 
The WISC scale will be performed in subjects age ≥6 years to ≤16 years old who are still 
ambulatory at time measurement. 
The WISC is individually administered intelligence test for children between ages of 6 and 
16. It generates a Full Scale Intelligence Quotient (IQ) (formerly known as an intelligence 
quotient or IQ score) that represents a child’s general intellectual ability. It also provides 
four primary index scores: Verbal Comprehension Index, Perceptual Reasoning Index, 
Working Memory Index, and Processing Speed Index. These indices represent a child’s 
abilities in discrete cognitive domains. It usually takes 45-65 minutes to administer. 

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7.7. Patient Reported Outcomes (PROs) 
7.7.1. EuroQoL 5 Dimension (EQ-5D-3L/EQ-5D-Y) 
The EQ-5D-3L is a questionnaire completed by the subject, designed to assess the subject’s 
current health and translate that score into an index value or utility score, providing a 
mechanism for conducting cost-effectiveness and cost-utility analyses.28 There are two 
components to the EQ-5D-3L: a Health State Profile and a visual analog scale (VAS) item. 
The Health State Profile is described in terms of 5 dimensions: mobility, self-care, usual 
activity, pain/discomfort, and anxiety/depression. The responses record three levels of 
severity (no problems/some or moderate problems/extreme problems) within a particular 
ED-5D dimension and are calculated to form a single index value. The EQ-5D-Y is a newly 
developed generic instrument measuring health-related quality of life in children and 
adolescents younger than 16 years old. It was adapted from the EQ-5D original 
questionnaire (http://www.euroqol.org/about-eq-5d.html). 
Both the EQ-5D-3L and EQ-5D-Y will be administered as paper questionnaires. EQ-5D-3L 
will be completed by subjects who are aged ≥16 years. EQ-5D-Y will be completed by 
subjects who are aged <16 years and able to read and complete the questionnaire. 
7.7.2. Healthcare Resource Utilization Questionnaire 
The HRU questionnaire is completed by the caregiver and asks questions about healthcare 
resources utilization related to their child’s use of healthcare professionals, emergency room 
visits, and hospitalizations during the course of the study. Caregivers are also asked to 
estimate out-of-pocket costs related to healthcare resource utilization (see Clinical Outcomes 
Assessment manual). The HRU will be administered as paper questionnaire. 
7.7.3. Work Productivity and Activity Impairment Questionnaire adapted for 
Caregiving 
The WPAI:CG is a self-reported measure of work productivity and impairment, to be 
completed by the caregiver, that yields four scores: Absenteeism (work time missed); 
Presenteeism (impairment at work/reduced on the job effectiveness); work productivity loss 
(overall work impairment/absenteeism plus presenteeism); and activity impairment. Each 
score is expressed as a percentage (0-100%) with higher numbers indicating greater 
impairment and less productivity (Reily et al, 1993; 
http://www.reillyassociates.net/Index.html; Clinical Outcomes Assessment manual). 
• Percent work time missed – a measure of absenteeism, calculated as work time 
missed due to health problem as a proportion of hours actually worked (Question 4). 
• Percent impairment while working – a measure of presenteeism, the degree to which 
health problem impacted work. 
• Percent overall work impairment – a measure of overall work productivity loss due to 
health problem, combining absenteeism plus presenteeism. 

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• Percent activity impairment – a measure of the degree to which health problem has 
affected ability to do regular activities other than work at a job. 
In this study, the WPAI:CG will measure the impact of a subject with DMD on a caregiver’s 
work productivity and regular activities. It will be administered as paper questionnaire. 
7.7.4. Pediatric Outcomes Data Collection Instrument 
In order to evaluate a subject’s functional health status, the PODCI questionnaire will be 
collected. The PODCI is a patient-reported assessment of musculoskeletal health intended 
for use in children and adolescents. The pediatric version is intended for completion by 
parents or caregivers of children ≤10 years old. The adolescent versions will be completed 
by subjects 11-18 years old and also by their parents or caregivers. The instrument is 
organized into multiple domains: upper extremity function, transfers and mobility, physical 
function and sports, comfort (pain free), happiness and satisfaction, and expectations for 
treatment. Each domain produces an independent score, and a total score is also computed. 
Scores may be reported as standardized, or they may be converted to normative scores based 
on the scores reported in a large, healthy population. 
The PODCI will be collected using a paper questionnaire when the subjects visit the study 
site. 
7.8. Rater Qualifications 
For specific assessments, only qualified raters will be allowed to evaluate and/or rate subjects 
in this study. The minimum qualifications a rater must meet for each study rating assessment 
will be outlined in the Functional Assessment manual provided to each participating site. 
The level of experience with the target population (or equivalent), specific scale experience 
(or equivalent), certification required (if applicable) will be listed and used to determine 
whether a rater is approved for a given assessment. Proposed raters who do not meet specific 
criteria but who may be qualified based on unique circumstances may be individually 
reviewed by the study clinical team to determine whether or not a waiver may be issued. The 
rater must become certified to perform selected study assessments before he or she can 
participate in the conduct of the study. For specifically defined assessments, rater training 
and standardization exercises may be conducted, and written and signed documentation will 
be provided by the site for each rater’s certification. In return, each site will be provided 
written and signed documentation outlining each rater’s certification for specific study 
assessments. Recertification may be required at periodic intervals during the study. The 
raters who administer specific study assessments will be documented in a centralized location 
and all site staff who administers ratings will be verified in the site study documentation 
during the conduct of the study. 

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8. SAFETY 
8.1. Adverse Events 
An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered related to 
the study intervention. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study intervention. 
Any AE that occurs from the time the participant consenting to the clinical research through 
and including 12 hours following the participant’s last visit must be recorded. The 
investigator is required to assess whether the AE may be related to the subject’s participation 
in the study. All AEs (ie, serious and non-serious, including those attributed to qualifying 
procedure identified as research-related injury) are collected in the clinical study database. 
The investigator must pursue and obtain information adequate to determine the outcome of 
the AE and to assess whether it meets the criteria for classification as a research related 
injury requiring immediate notification to Pfizer as described below. 
8.2. Research Related Injury 
Should a subject, in the investigator’s opinion, suffer a medically important research-related 
injury caused by their participation in the study, the designated Pfizer clinician or medical 
monitor must be notified immediately. 
A medically important research-related injury is any untoward medical occurrence that: 
• Results in death; 
• Is life-threatening (immediate risk of death); 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
• Results in congenital anomaly/birth defect. 
Medical and scientific judgment is exercised in determining whether an injury is an 
important medical event. An important medical event may not be immediately 
life-threatening and/or result in death or hospitalization. However, if it is determined that the 
event may jeopardize the subject or may require intervention to prevent one of the other 
outcomes listed in the definition above, the important medical event should be reported as a 
research-related injury. 

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An investigator may be requested by the designated Pfizer clinician or medical monitor to 
obtain specific additional follow-up information in an expedited fashion. In general, this will 
include a description of the injury in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality. Information on 
other possible causes of the event, such as concomitant treatments, vaccines, and/or illnesses 
must be provided. In the case of a subject death, a summary of available autopsy findings 
must be submitted as soon as possible to Pfizer or its designated representative. 
9. DATA ANALYSIS/STATISTICAL METHODS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor. The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment. 
9.1. Sample Size Determination 
No formal statistical sample size computation based on hypothesis testing and power is 
performed for this study. Total sample size of this study is 330, drop out is estimated to be 
10%, and this sample size is acceptable for analyses of DMD natural history. 
The target enrollment for each of the 3 groups and corresponding anticipated precision for 
estimates of key outcome measures based on literature are listed below: 
• Group 1, Ambulatory subjects aged <6 years: approximately 100 subjects. There will 
be ≥90 subjects following anticipated drop out. 
• Group 2, Ambulatory patients aged ≥6 years: approximately 180 subjects. There will 
be ≥162 subjects following anticipated drop out. 
• Group 3, Non-ambulatory subjects: approximately 50 subjects. There will be 
≥45 subjects following anticipated drop out. 
9.2. Efficacy Analysis 
9.2.1. Analysis of the Primary Endpoint 
To characterize the natural history of Chinese DMD subjects, all efficacy endpoints listed in 
Section 2 for this objective will be analyzed as follows: 
• For continuous endpoints: descriptive statistics using sample size, mean, standard 
deviation, median, minimum and maximum. 
• For categorical endpoints: descriptive statistics using count and percentage. 
• For time-to-event endpoints: estimates of median event-free time and survival 
probabilities by Kaplan-Meier method. 

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Additional disease progression modeling will be performed to quantify the time course of 
changes for the selected relevant endpoints, including their correlations with each other and 
their relationship with the time-to-event endpoints. Detailed methodology for the disease 
progression modelling will be documented in a Population Modelling and Analysis Plan 
(PMAP), which will be dated, filed and maintained by the sponsor. Results will be reported 
in a Population Modelling and Analysis Report (PMAR). 
9.2.2. Analysis of Secondary Endpoints 
To characterize the prevalence of mutation types in Chinese DMD subjects, descriptive 
statistics will be reported for the proportion of subjects with mutation of exon deletions, exon 
duplications, point mutation, small insertion, small deletion, andothers. The propportion of 
each affected exon by mutation types will also be reported, along with the proportion of 
subjects with any mutation affecting any exon between exon 9 and exon 13, inclusive, or a 
deletion that affects both exon 29 and exon 30. 
To characterize the quality of life in Chinese DMD patients, quality of life endpoints will be 
summarized by descriptive statistics.. 
To assess the health care utilization in Chinese DMD subjects, health care utility endpoints 
will be summarized by descriptive statistics. 
9.3. Safety Analysis 
All safety endpoints collected in this study will be reported using the Pfizer Data Standard. 
9.4. Interim Analysis 
No formal interim analysis will be conducted for this study. 
10. QUALITY CONTROL AND QUALITY ASSURANCE 
Pfizer or its agent will conduct periodic monitoring visits during the study conduct, to ensure 
that the protocol and Good Clinical Practices (GCPs) are being followed. The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate. The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification. This 
verification may also occur after study completion. 
During study conduct and/or after study completion, the investigator site may be subject to 
review by the RB/Ethics Committee (EC) and/or quality assurance audits performed by 
Pfizer, or companies working with or on behalf of Pfizer, and/or to inspection by appropriate 
regulatory authorities. 
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
and/or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection. The investigator site and 
investigator will promptly resolve any discrepancies that are identified. The investigator will 
promptly provide copies of the inspection findings to Pfizer or its agent. Before response 

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submission to the regulatory authorities, the investigator will provide Pfizer or its agents with 
an opportunity to review and comment on responses to any such findings. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 
11. DATA HANDLING AND RECORD KEEPING 
11.1. Case Report Forms/Data Collection Tools/Electronic Data Record 
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
A CRF is required and should be completed for each included subject. The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. The investigator shall ensure that the 
CRFs[/DCTs] are securely stored at the study site in [encrypted electronic and/or paper] form 
and will be [password protected or secured in a locked room] to prevent access by 
unauthorized third parties. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required. The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases the source documents are the hospital or the physician’s chart. In these cases, 
data collected on the CRFs must match those charts. 
In some cases, the CRF may also serve as the source document. In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document. 

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11.2. Record Retention 
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent/assent documents, copies of all CRFs, safety reporting forms, source 
documents, detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports). The records should 
be retained by the investigator according to the International Conference on Harmonisation 
(ICH) guidelines, according to local regulations, or as specified in the clinical study 
agreement (CSA), whichever is longer. The investigator must ensure that the records 
continue to be stored securely for so long as they are retained. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified. The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations. 
The investigator must obtain Pfizer’s written permission before disposing of any records, 
even if retention requirements have been met. 
12. ETHICS 
12.1. Institutional Review Board/Ethics Committee 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent/assent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC. All correspondence with the 
IRB/EC should be retained in the investigator file. Copies of IRB/EC approvals should be 
forwarded to Pfizer. 
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation. 
12.2. Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki. 

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12.3. Subject Information and Consent 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of subject personal data. Such 
measures will include omitting subject names or other directly identifiable data in any 
reports, publications, or other disclosures, except where required by applicable laws. 
The personal data will be stored at the study site in encrypted electronic and paper form and 
will be secured in a locked room to ensure that only authorized study staff have access. The 
study site will implement appropriate technical and organizational measures to ensure that 
the personal data can be recovered in the event of disaster. In the event of a potential 
personal data breach, the study site shall be responsible for determining whether a personal 
data breach has in fact occurred and, if so, providing breach notifications as required by law. 
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer and other authorized 
parties, subject names will be removed and will be replaced by a single, specific, numerical 
code, based on a numbering system define by Pfizer subject. All other identifiable data 
transferred to Pfizer or other authorized parties will be identified by this single, 
subject-specific code. The investigator site will maintain a confidential list of subjects who 
participated in the study, linking each subject’s numerical code to his or her actual identity. 
In case of data transfer, Pfizer will maintain high standards of confidentiality and protection 
of subject’s personal data, consistent with the Clinical Study Agreement and applicable 
privacy laws. 
The informed consent/assent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws. The informed consent/assent documents used during the informed 
consent process and any subject recruitment materials must be reviewed and approved by 
Pfizer, approved by the IRB/EC before use, and available for inspection. The investigator 
must ensure that each study subject, or his or her legally acceptable representative, or 
parent(s) or legal guardian if a minor, is fully informed about the nature and objectives of the 
study, the sharing of data relating to the study and possible risks associated with 
participation, , including the risks associated with the processing of the subject’s personal 
data. The investigator further must ensure that each study subject, or his legally acceptable 
representative, or parent(s) or legal guardian if a minor, is fully informed about his right to 
access and correct his personal data and to withdraw consent for the processing of his 
personal data. 
Whenever consent is obtained from a subject’s legally acceptable representative/parent(s) or 
legal guardian, the subject’s assent (affirmative agreement) must subsequently be obtained 
when the subject has the capacity to provide assent, as determined by the IRB/EC. If the 
investigator determines that a subject’s decisional capacity is so limited that he or she cannot 
reasonably be consulted, then, as permitted by the IRB/EC and consistent with local 
regulatory and legal requirements, the subject’s assent may be waived with source 
documentation of the reason assent was not obtained. If the study subject does not provide 
his or her own consent, the source documents must record why the subject did not provide 
consent (eg, minor, decisionally impaired adult), how the investigator determined that the 

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person signing the consent was the subject’s legally acceptable representative, the consent 
signer’s relationship to the study subject (eg, parent, spouse), and that the subject’s assent 
was obtained or waived. If assent is obtained verbally, it must be documented in the source 
documents. 
If the study includes minor subjects who reach the age of majority during the study, as 
recognized under local law, they must re-consent as adults to remain in the study. If the 
enrollment of emancipated minors is permitted by the study age criteria, the IRB/EC, and 
local law, they must provide documentation of legal status to give consent without the 
permission of a parent or legal guardian. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or the subject’s legally acceptable representative, parent(s), or 
legal guardian and the subject’s assent, when applicable, before any study-specific activity is 
performed, unless a waiver of informed consent has been granted by an IRB/EC. The 
investigator will retain the original of each subject’s signed consent/assent document. 
13. PUBLICATIONS BY INVESTIGATORS 
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product. However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed. 
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days. 
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results. 
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section. 
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II – “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors. 

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Publication of study results is also provided for in the CSA between Pfizer and the 
institution. In this section entitled PUBLICATIONS BY INVESTIGATORS, the defined 
terms shall have the meanings given to them in the CSA. 
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control. If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues. 

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14. REFERENCES 
1. 
Biggar WD. Duchenne muscular dystrophy. Pediatr Rev 2006;27(3):83-8. 
2. 
McDonald CM, Henricson EK, Abresch RT, et al. The 6-minute walk test and other 
endpoints in Duchenne muscular dystrophy: longitudinal natural history observations 
over 48 weeks from a multicenter study. Muscle Nerve 2013;48(3):343-56. 
3. 
Emery AEH. Population frequencies of inherited neuromuscular diseases-a world 
survey. Neuromuscul Disord 1991; 1(1):19-29. 
4. 
Centers for Disease Control and Prevention (CDC). Prevalence of Duchenne/Becker 
muscular dystrophy among males aged 5-24 years – four states, 2007. MMWR Morb 
Mortal Wkly Rep 2009; 58(40):1119-22. 
5. 
Mazzone ES, Pane M, Sormani MP, et al. 24month longitudinal data in ambulant boys 
with Duchenne muscular dystrophy. PloS One 2013;8:e52512. 
6. 
McDonald CM, Henricson EK, Abresch RT, et al. The cooperative international 
neuromuscular research group Duchenne natural history study–a longitudinal 
investigation in the era of glucocorticoid therapy: design of protocol and the methods 
used. Muscle Nerve 2013;48:32–54. 
7. 
Henricson EK, Abresch RT, Cnaan A, et al. The cooperative international 
neuromuscular research group Duchenne natural history study: glucocorticoid treatment 
preserves clinically meaningful functional milestones and reduces rate of disease 
progression as measured by manual muscle testing and other commonly used clinical 
trial outcome measures. Muscle Nerve 2013;48:55–67. 
8. 
Manzur AY, Kuntzer T, Pike M, et al. Glucocorticoid corticosteroids for Duchenne 
muscular dystrophy. Cochrane Database Syst Rev 2008;(1):CD003725. 
9. 
Ricotti V, Ridout DA, Scott E, et al. Long-term benefits and adverse effects of 
intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. 
J Neurol Neurosurg Psychiatry 2013;84:698–705. 
10. Kieny P, Chollet S, Delalande P, Le Fort M, Magot A, Pereon Y, et al. Evolution of life 
expectancy of patients with Duchenne muscular dystrophy at AFM Yolaine de Kepper 
centre between 1981 and 2011. Ann Phys Rehabil Med 2013;56:443e54. 
11. Jeppesen J, Green A, Steffensen BF, Rahbek J. The Duchenne muscular dystrophy 
population in Denmark, 1977–2001: prevalence, incidence and survival in relation to 
the introduction of ventilator use. Neuromuscul Disord 2003; 13: 804–12. 
12. Anthony K, Arechavala-Gomeza V, Ricotti V, et al. Biochemical characterization of 
patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 
skipping. JAMA Neurol 2014;71:32–40. 

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13. van den Bergen JC, Wokke BH, Janson AA, et al. Dystrophin levels and clinical 
severity in Becker muscular dystrophy patients. J Neurol Neurosurg Psychiatry 
2014;85:747–53. 
14. Li X, Zhao L, Hu C, et al. A comprehensive database of Duchenne and Becker muscular 
dystrophy patients in Children’s Hospital of Fudan University. Chin J Contemp Neurol 
Neeurosurg. 2015;15(5):360-8. 
15. Tuffery-Giraud S, Beroud C, Leturcq F, et al. Genotype - phenotype analysis in 
2,405 patients with a dystrophinopathy using the UMD - DMD database: a model of 
nationwide knowledge base. Hum Mutat, 2009, 30:934-945. 
16. Yang J, Li SY, Li YQ, et al. MLPA-based genotype-phenotype analysis in 
1053 Chinese patients with DMD/BMD. BMC Med Genet. 2013;14:29. 
17. Mazzone ES, Pane M, Sormani MP, et al. Correction: 24 month longitudinal data in 
ambulant boys with duchenne muscular dystrophy. PloS ONE 2013;8. 
18. Bello L, Morgenroth LP, Gordish-Dressman H, et al. DMD genotypes and loss of 
ambulation in the CINRG Duchenne Natural History Study. Neurology 
2016;87(4):401-9. 
19. Connolly AM, Florence JM, Zaidman CM, et al. Clinical trial readiness in 
nonambulatory boys and men with duchenne muscular dystrophy: MDA-DMD network 
follow-up. Muscle Nerve 2016; 54(4):681-9. 
20. Mayer OH, Finkel RS, Rummey C, et al. Characterization of pulmonary function in 
Duchenne Muscular Dystrophy. Pediatr Pulmonol 2015; 50(5):487-94. 
21. Mazzone ES, Coratti G, Sormani MP, et al. Timed rise from floor as a predictor of 
disease progression in Duchenne muscular dystrophy: an observational study. PloS One 
2016; 11(3):e0151445. 
22. Gauld LM, et al. Height prediction from ulna length. Dev Med Child Neurology 2004 
Jul 46(7): 475-80. 
23. Quanjer, PH, Stanojevic, S, Cole, TJ, et al. Multi-ethnic reference values for spirometry 
for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 
2012;40(6):1324-43. 
24. Birnkrant, DJ, Bushby, K, Bann, CM, et al. Diagnosis and management of Duchenne 
muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic 
management. Lancet Neurol. 2018;17(4):347-61. 
25. Mazzone ES, Messina S, Vasco G, et al. Reliability of the North Star Ambulatory 
Assessment in a multicentric setting. Neuromuscul Disord 2009; 19(7):458-61. 

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26. Mazzone E, Martinelli D, Berardinelli A, et al. North Star Ambulatory Assessment, 
6-minute walk test and timed items in ambulant boys with Duchenne muscular 
dystrophy. Neuromuscul Disord 2010; 20(11):712-6. 
27. Mayhew A, Mazzone ES, Eagle M, et al. Development of the Performance of the Upper 
Limb module for Duchenne muscular dystrophy. Developmental Medicine & Child 
Neurology 2013;55(11):1038-45. 
28. The development of new research methods for the valuation of EQ-5D-5L. European 
Journal of Health Economics. 2013;14(1). 

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Appendix 1. Protocol Amendment History 
The protocol amendment summary of changes table for the current amendment is located 
directly before the TOC. The protocol amendment summary of changes tables for past 
amendment(s) can be found below: 
 
Document 
Version Date 
Summary of Changes and Rationale 
Amendment 1 
14-Sep-2020 
1. Removed Expanded Hammersmith 
Functional Motor Scale and related 
endpoints. 
• HFMSE is not an appropriate motor 
functional assessment for DMD patients. 
2. Removed 4 Stair Climb (4SC) and related 
endpoints. 
• 4SC is unlikely to change significantly 
with approximately 1 to 2 years of 
observation based on results from a 
completed Pfizer Phase 2 DMD study. 
3. Removed Six Minute Walk Test (6MWT) 
and related endpoints. 
• The 10 meter walk/run test (part of the 
NSAA) is a more appropriate measure of 
ambulatory function than the 6MWT for 
patients with DMD. 
4. Changed the primary endpoint forced vital 
capacity (FVC) to percent predicted forced 
vital capacity (%pFVC) 
• %pFVC was recommended as an endpoint 
in DMD studies by experts in the DMD 
field. Using %pFVC rather than absolute 
FVC allows for continuous assessment 
across a broad range of ages in which 
growth impacts the absolute FVC and will 
aid contextualizing the findings with other 
studies. 
5. Modified subgroup enrollment criteria to 
keep enrollment plan consistent with data 
analysis plan of ambulatory or non- 

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Document 
Version Date 
Summary of Changes and Rationale 
ambulatory and inalignment with clinical 
practice. 
6. Removed rationale of sample size 
justification. 
7. Updated age requirement of Performance of 
Upper Limb 2.0 (PUL 2.0) to be in subjects 
≥10 years old. 
• PUL 2.0 is unlikely to change 
significantly in subjects younger than 
10 years old based on published natural 
history data. 
8. Removed ventricular systolic pressure as not 
used for clinical monitoring in DMD patients 
and cannot be obtained accurately via 
Echocardiogram. 
9. Allowed to collect Urea if Blood Urea 
Nitrogen (BUN) is not available. 
10. Clarified the age requirements on EQ-5D-Y 
and EQ-5D-3L. 
11. Included all changes in previous Protocol 
Administrative Changes Letters. 
• Corrected the mistake of involving 
Month 36 visit on Quality of Life 
variables and related endpoints, includes 
Pediatric Outcomes Data Collection 
Instrument (PODCI), EuroQoL 
5 Dimension 3 Level (EQ-5D- 
3L)/EuroQoL 5 Dimension Youth 
(EQ-5D-Y), Healthcare Resource 
Utilization (HRU), and Work Productivity 
and Activity Impairment Questionnaire 
adapted for Caregiving (WPAI:CG). 
• Updated and clarifiedthe definition and 
requirements of Caregiver and related text. 
• Updated the instruction text of Wechsler 
Intelligence Scale for Children (WISC) to 

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Document 
Version Date 
Summary of Changes and Rationale 
allow use of WISC version IV instead of 
version V, as there is no available 
version V in Chinese. 
• Provided correct Appendix 2 EQ-5D-Y. 
• Allow to collect Cardiac Troponin T if 
Cardiac Troponin I is not available. 
• Clarified the requirement in Section 6.2 to 
complete all assessments within 
2 consecutive days and at approximately 
the same time of day. Section 6, 6.1, 
6.3 were also updated accordingly to 
ensure consistency. 
• Revised the exclusion criteria and the 
related text by removing requirement of 
completing the recommended national 
immunization schedule to comply with 
local requirements. 
• Corrected and clarified that“Actional 
bicarbonate (HCO3-)” is the component to 
be collected for Bicarbonate assessment. 
• Updated the appendix of Healthcare 
Resource Utilization Questionnaire to use 
latest version. 
12. Updated Section 6.4 and Section 8.1 to 
incorporate latest requirement on participant 
discontinuation/withdrawal and safety, 
corresponding to Section 7.2 and Section 
8.3.1 in latest methodology study protocol 
template. 
13. Provided clarifying text where necessary. 
14. Updated SOA to reflect corrections, changes 
and updates to assessments. 
15. Updated Appendix 6. Abbreviations to 
reflect changes. 

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Document 
Version Date 
Summary of Changes and Rationale 
16. Original reference #23 was removed (due to 
removal of 6MWT) and added new 
references as #23 and #24 (due to the 
endpoint of FVC was changed to %pFVC), 
making original reference #24, #25, #26 and 
#27 now reference #25, #26, #27 and #28, 
and the original references #28, #29, #30 and 
#31 were removed (due to removal of sample 
size justification). 
17. Corrected typographical errors. 
Original protocol 
15 May 2018 
Not applicable (N/A) 

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Appendix 2. Abbreviations 
This following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
%pFVC 
Percent predicted forced vital capacity 
%p FEV1 
Percent predicted forced expiratory volume in one second 
AE 
adverse event 
BMD 
Becker muscular dystrophy 
CE 
clinical evaluator 
CI 
confidence interval 
CRF 
case report form 
CSA 
clinical study agreement 
DMD 
Duchenne muscular dystrophy 
EC 
ethics committee 
ECG 
electrocardiogram 
EQ-5D-3L 
EuroQoL 5 Dimensions 3 Levels 
EQ-5D-Y 
EuroQoL 5 Dimensions – Youth 
FEV1 
forced expiratory volume in one second 
EoS 
end of study 
FVC 
forced vital capacity 
GC 
glucocorticoid 
GCP 
Good Clinical Practice 
HR 
heart rate 
HRU 
Healthcare Resource Utilization 
ICH 
International Conference on Harmonisation 
IQ 
intelligence quotient 
IRB 
institutional review board 
LVEF 
left ventricular ejection fraction 
N/A 
not applicable 
NSAA 
North-Star Ambulatory Assessment 
MEP 
maximum expiratory pressure 
MIP 
maximum inspiratory pressure 
MP 
master physiotherapist 
PI 
principal investigator 
PMAP 
Population Modelling and Analysis Plan 
PMAR 
Population Modelling and Analysis report 
PODCI 
Pediatric Outcomes Data Collection Instrument 
PRO 
Patient Reported Outcome 
PUL 
Performance of Upper Limb 
ROM 
range of motion 
SAP 
statistical analysis plan 
SOC 
standard of care 
TA 
therapeutic area 
VAS 
visual analog scale 

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Abbreviation 
Term 
WISC 
Wechsler Intelligence Scale for Children 
WPAI:CG 
Work Productivity and Activity Impairment Questionnaire 
adapted for Caregiving