A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG TERM SAFETY OF PF-06252616 IN BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Sponsor: Pfizer

PF-06252616
B5161004
Final Protocol, 08 April 2016
Page 1
CLINICAL PROTOCOL
A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO EVALUATE THE 
LONG TERM SAFETY OF PF-06252616 IN BOYS WITH DUCHENNE MUSCULAR 
DYSTROPHY
Compound:
PF-06252616
Compound Name:
Anti-myostatin
United States (US) Investigational New 
Drug (IND) Number:
113,863
European Clinical Trials Database 
(EudraCT) Number:
2016-001615-21
Protocol Number:
B5161004
Phase:
2
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Document History
Document
Version Date
Summary of Changes
Original Protocol
08 April 2016
Not applicable (N/A)
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TABLE OF CONTENTS
APPENDICES ...........................................................................................................................8
PROTOCOL SUMMARY.........................................................................................................9
Background ......................................................................................................................9
Objectives and Endpoints.................................................................................................9
Objectives ...............................................................................................................9
Endpoints................................................................................................................9
Clinical Outcome Assessments (COA) ................................................................10
Study Design.........................................................................................................10
Study Treatments..................................................................................................11
Statistical Methods................................................................................................11
Safety Analysis.......................................................................................11
Analysis of efficacy and PD endpoints.................................................................11
Analysis of PK and Immunogenicity....................................................................11
Analysis of Clinical Outcomes Assessments (Caregiver and patient-
reported)...........................................................................................................11
1. INTRODUCTION ...............................................................................................................21
1.1. Mechanism of Action/Indication.............................................................................21
1.2. Background and Rationale ......................................................................................21
1.2.1. Myostatin Role in Muscle Regulation ........................................................21
1.2.2. Duchenne Muscular Dystrophy..................................................................21
1.2.3. PF-06252616...............................................................................................22
1.3. Clinical Experience with PF-06252616 ..................................................................22
1.4. Rationale for Dosage Selection and Method of Administration .............................23
1.5. Study Design Rationale...........................................................................................23
1.6. Anticipated Risks and Safety Monitoring ...............................................................23
1.6.1. Hepatic Injury.............................................................................................23
1.6.2. Gastric Erosion and Haemorrhage..............................................................24
1.6.3. Accelerated Sexual Development...............................................................24
1.6.4. Bone Metabolism........................................................................................24
1.6.5. Cardiac........................................................................................................24
1.6.6. Radiation.....................................................................................................25
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1.6.7. Other Risks .................................................................................................25
1.6.8. Other Safety Monitoring.............................................................................25
1.7. Summary of Risk Benefit........................................................................................25
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................25
2.1. Objectives................................................................................................................25
2.1.1. Primary Objective.......................................................................................25
2.1.2. Secondary Objectives .................................................................................26
2.1.3. Exploratory Objectives ...............................................................................26
2.2. Endpoints.................................................................................................................26
2.2.1. Primary endpoints.......................................................................................26
2.2.1.1. Safety.........................................................................................26
2.2.2. Secondary endpoints...................................................................................27
2.2.2.1. Efficacy .....................................................................................27
2.2.2.2. PK and Immunogenicity............................................................27
2.2.3. Exploratory Endpoints................................................................................27
2.2.3.1. PD..............................................................................................27
2.2.3.2. Clinical Outcome Assessments .................................................27
3. STUDY DESIGN.................................................................................................................28
3.1. Study Overview.......................................................................................................28
3.2. Duration of Study and Subject Participation...........................................................28
3.3. Planned Number of Subjects...................................................................................29
3.4. Safety Monitoring and the E-DMC.........................................................................29
3.4.1. External Data Monitoring Committee (E-DMC)........................................29
4. SUBJECT SELECTION......................................................................................................29
4.1. Inclusion Criteria.....................................................................................................29
4.2. Exclusion Criteria....................................................................................................30
4.3. Enrolment................................................................................................................31
4.4. Lifestyle Guidelines ................................................................................................31
4.4.1. Meals and Dietary Restrictions...................................................................31
4.4.2. Activity .......................................................................................................32
4.4.3. Contraception..............................................................................................32
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4.5. Caregiver(s).............................................................................................................33
4.6. Sponsor’s Qualified Medical Personnel..................................................................33
4.7. Rater Qualifications.................................................................................................34
4.7.1. Columbia-Suicide Severity Rating Scale (C-SSRS)...................................34
4.7.2. Tanner Stage and Testicular Volume .........................................................34
4.7.3. Clinical Evaluators (CEs) ...........................................................................34
5. STUDY TREATMENTS.....................................................................................................34
5.1. Allocation to Treatment ..........................................................................................35
5.2. Blinding...................................................................................................................36
5.3. Subject Compliance.................................................................................................36
5.4. Investigational Product Supplies.............................................................................36
5.4.1. Dosage Form(s) and Packaging..................................................................36
5.4.2. Preparation and Dispensing........................................................................36
5.5. Investigational Product Administration ..................................................................37
5.5.1. Infusion Reaction........................................................................................37
5.6. Investigational Product Storage ..............................................................................38
5.7. Investigational Product Accountability...................................................................39
5.7.1. Destruction of Investigational Product Supplies ........................................39
5.8. Concomitant Treatment(s).......................................................................................39
5.8.1. Permitted Therapies....................................................................................39
5.8.2. Prohibited Therapies...................................................................................40
6. STUDY PROCEDURES .....................................................................................................40
6.1. Informed Consent/Assent........................................................................................41
6.2. Procedures ...............................................................................................................41
6.3. Subject Withdrawal.................................................................................................44
6.4. Lost to follow-up:....................................................................................................45
7. ASSESSMENTS..................................................................................................................45
7.1. Blood Volume .........................................................................................................45
7.2. Safety.......................................................................................................................46
7.2.1. Clinical Laboratory.....................................................................................46
7.2.2. Physical Examinations/Nose and Throat Exam..........................................47
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7.2.3. Tanner Stage and Testicular Volume .........................................................48
7.2.4. Vitals...........................................................................................................48
7.2.5. Electrocardiogram (ECG)...........................................................................48
7.2.6. Cardiac MRI/Echocardiogram....................................................................49
7.2.7. Assessment of Suicidal Ideation and Behavior –Columbia Suicide 
Severity Rating Scale (C-SSRS)......................................................................50
7.3. Banked Biospecimens .............................................................................................50
7.3.1. Markers of Drug Response.........................................................................50
7.3.2. Additional Research....................................................................................52
7.4. Pharmacokinetics (Serum for Analysis of PF-06252616).......................................52
7.5. Anti-Drug Antibody (ADA) anti-PF-06252616 and Neutralizing Antibody 
(NAb).........................................................................................................................52
7.6. PK and Immunogenicity Sample Shipment ............................................................53
7.7. Imaging Assessments ..............................................................................................53
7.7.1. Liver MRI...................................................................................................53
7.7.2. Dual-energy X-ray Absorptiometry (DXA) and X-ray ..............................53
7.7.2.1. DXA ..........................................................................................53
7.7.2.2. X-ray..........................................................................................54
7.7.2.3. Radiation Exposure ...................................................................54
7.8. Functional Assessments ..........................................................................................54
7.8.1. Pulmonary Function Tests (PFTs)..............................................................55
7.8.2. 4 Stair Climb (4SC) ....................................................................................55
7.8.3. Northstar Ambulatory Assessment (NSAA) ..............................................55
7.8.4. Range of Motion (ROM) ............................................................................56
7.8.5. Strength Assessment...................................................................................56
7.8.6. Performance of Upper Limb (PUL)............................................................56
7.8.7. Six Minute Walk Test (6MWT) .................................................................56
7.9. Triggered Requirements..........................................................................................57
7.10. Infusion Site Monitoring .......................................................................................57
7.11. Clinical Outcome Assessments (Caregiver completed)........................................57
7.11.1. Pediatric Outcomes Data Collection Instrument (PODCI).......................57
7.11.2. Zarit Burden Inventory (ZBI) ...................................................................57
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7.11.3. EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L) ........................................58
7.11.4. Work Productivity and Activity Impairment Questionnaire adapted 
for Caregiving (WPAI:CG)..............................................................................58
7.11.5. Healthcare Resource Utilization (HRU) questionnaire ............................59
7.12. Clinical Outcome Assessments (Subject completed)............................................59
7.12.1. Pediatric Outcomes Data Collection Instrument (PODCI).......................59
7.12.2. EuroQol 5 Dimensions - Youth................................................................59
8. ADVERSE EVENT REPORTING......................................................................................60
8.1. Adverse Events........................................................................................................60
8.2. Reporting Period .....................................................................................................60
8.3. Definition of an Adverse Event...............................................................................60
8.4. Medication Errors....................................................................................................61
8.5. Abnormal Test Findings..........................................................................................62
8.6. Serious Adverse Events...........................................................................................62
8.6.1. Protocol-Specified Serious Adverse Events...............................................63
8.6.2. Potential Cases of Drug-Induced Liver Injury............................................63
8.7. Hospitalization ........................................................................................................64
8.8. Severity Assessment................................................................................................65
8.9. Causality Assessment..............................................................................................66
8.10. Exposure During Pregnancy..................................................................................66
8.11. Occupational Exposure .........................................................................................67
8.12. Withdrawal Due to Adverse Events (See Also the Section on Subject 
Withdrawal)...............................................................................................................68
8.13. Eliciting Adverse Event Information ....................................................................68
8.14. Reporting Requirements........................................................................................68
8.14.1. Serious Adverse Event Reporting Requirements .....................................68
8.14.2. Nonserious Adverse Event Reporting Requirements ...............................69
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities ................69
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................69
9.1. Sample Size Determination.....................................................................................69
9.2. Safety Analysis........................................................................................................69
9.3. Efficacy Analysis ....................................................................................................70
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9.3.1. Analysis of efficacy and PD endpoints.......................................................70
9.3.2. Analysis of PK and Immunogenicity..........................................................70
9.4. Exploratory Analyses ..............................................................................................70
9.4.1. Clinical Outcome Assessments...................................................................70
9.5. Interim Analysis ......................................................................................................70
9.6. Data Monitoring Committee ...................................................................................70
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................71
11. DATA HANDLING AND RECORD KEEPING .............................................................71
11.1. Case Report Forms/Electronic Data Record .........................................................71
11.2. Record Retention...................................................................................................72
12. ETHICS..............................................................................................................................72
12.1. Institutional Review Board/Ethics Committee......................................................72
12.2. Ethical Conduct of the Study ................................................................................73
12.3. Subject Information and Consent..........................................................................73
12.4. Subject Recruitment ..............................................................................................74
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................74
13. DEFINITION OF END OF TRIAL...................................................................................74
13.1. End of Trial in a Member State.............................................................................74
13.2. End of Trial in All Other Participating Countries.................................................74
14. SPONSOR DISCONTINUATION CRITERIA ................................................................75
15. PUBLICATION OF STUDY RESULTS..........................................................................75
15.1. Communication of Results by Pfizer ....................................................................75
15.2. Publications by Investigators ................................................................................76
16. REFERENCES ..................................................................................................................77
APPENDICES
Appendix 1. Abbreviations......................................................................................................79
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PROTOCOL SUMMARY
Background
This study is an open-label extension (OLE) to Protocol B5161002 and will provide an 
assessment of the long term safety, efficacy, pharmacodynamics (PD) and pharmacokinetics 
(PK) of intravenous (IV) dosing of PF-06252616 in boys with Duchenne muscular dystrophy 
(DMD).
Objectives and Endpoints
Objectives

To evaluate the long-term safety of IV dosing of PF-06252616 in boys with DMD.

To evaluate the long-term efficacy of PF-06252616 using functional assessments and 
strength.

To assess the PK and immunogenicity of PF-06252616.

To evaluate PD markers that may be informative in demonstrating the pharmacologic 
effect of PF-06252616.

To evaluate the long-term functional health effects of PF-06252616 on Pediatric 
Outcomes Data Collection Instrument (PODCI) Parent-report and Adolescent self-report
scores.

To assess the long-term effects of PF-06252616 on health-related quality of life (HRQL) 
and healthcare resource utilization (HRU) in boys with DMD.

To evaluate the long-term effects of PF-06252616 on caregiver burden, HRQL and work 
productivity and activity impairment.

To collect exploratory biomarker samples for biobanking.
Endpoints

Safety:

Incidence and/or rate of intolerability or dose limiting treatment related adverse 
events (AEs).

Incidence and/or rate, severity and causal relationship of treatment emergent adverse 
events (TEAEs) and withdrawals due to TEAEs.

Incidence and magnitude of abnormal laboratory findings.

Abnormal and clinically relevant changes in liver magnetic resonance imaging (MRI)
and physical examinations.
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
Efficacy:

Baseline values and change from baseline in the following functional assessment 
tests; Pulmonary function test (PFTs) (to include forced vital capacity [FVC], forced 
expiratory volume in 1 second [FEV1] and peak expiratory flow rate [PEFR]), 4 Stair 
Climb (4SC), Northstar Ambulatory Assessment (NSAA), Performance of Upper 
Limb (PUL), Range of motion (ROM) and 6 minute walk distance (6MWD).

Mean change from baseline in muscle strength measured by myometry.

PK and Immunogenicity:

Trough serum PF-06252616 concentrations for all subjects receiving active drug.

Incidence of anti-drug antibody (ADA) and neutralizing antibody (NAb).

PD:

Change from baseline of Lean Body Mass (LBM) determined via whole body dual 
image x-ray absorptiometry (DXA).
Clinical Outcome Assessments (COA)

Change from baseline in the Pediatric Outcomes Data Collection Instrument (PODCI) 
Parent-report and Adolescent self-report scores.

Change from baseline in the EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) Health 
Questionnaire.

Change from baseline in the EuroQol 5 Dimensions - Youth (EQ-5D-Y) Health 
Questionnaire.

Change from baseline in the Healthcare Resource Utilization (HRU) questionnaire.

Change from baseline in Zarit Burden Interview (ZBI).

Change from baseline in the Work Productivity and Activity Impairment Questionnaire 
adapted for caregiving (WPAI:CG) in the percent work time missed, percent impairment 
while working, percent overall work impairment, and percent activity impairment due to 
a child’s Duchenne muscular dystrophy.
Study Design
Approximately 105 eligible subjects will be assigned to receive an individualized maximum 
tolerated dose based on their tolerability profile/data from B5161002.  No placebo 
comparator will be assessed. Consenting subjects who complete the B5161002 study will be
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invited to transition directly to the OLE study.  Subjects’ results from the B5161002 study 
may be used as screening data for the current study.
Study Treatments
The individual dose level selected for each subject will be based on the maximum tolerated 
dose from the parent Study B5161002.  Subjects will be dosed with one of three 
PF-06252616 dose levels: 5 mg/kg, 20 mg/kg or 40 mg/kg.
Statistical Methods
Safety Analysis
Summary statistics will be performed on the following safety endpoints:

Incidence and/or rate of intolerability or dose limiting treatment related AEs.

Incidence and/or rate, severity and causal relationship of TEAEs and withdrawals due to 
TEAEs.

Incidence and magnitude of abnormal laboratory findings.

Abnormal and clinically relevant changes in liver MRI and physical examinations.
Analysis of efficacy and PD endpoints
Baseline values, change from baseline to last visit in PFTs, 4SC, NSAA, PUL, 6MWD,
muscle strength by myometry and lean body mass by DXA will be described based on 
summary statistics including minimum, median, mean, maximum, and standard deviation. 
Change from baseline may also be assessed for any or all intermediate visits.
Analysis of PK and Immunogenicity

Summary statistics will be provided for trough serum concentrations by dose.

Incidence of ADA and NAb.
Analysis of Clinical Outcomes Assessments (Caregiver and patient-reported)
Summary statistics will be presented for the PODCI, EQ-5D-Y, EQ-5D-3L, Zarit Burden 
Interview, WPAI-CG, and HRU by baseline, treatment and time point as applicable.  
Methodology for any treatment group comparisons will be specified in the statistical analysis 
plan (SAP).
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SCHEDULE OF ACTIVITIES
The Schedule of Activities tables provide an overview of the protocol visits and procedures for Year 1, Years 2-4 and Early 
Withdrawal. In order to accommodate the scheduling, assessments may be conducted on separate days within the visit window. Refer 
to the 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 on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the wellbeing of the subject.
Study Flowchart: Year 1
Year 1
Visit Numbera
Screena
1
2
3
4
5
6
7
8
9
10
11
12
13
Study Weeka
1
5
9
13
17
21
25
29
33
37
41
45
49
Study Daya
1
29
57
85
113
141
169
197
225
253
281
309
337
Visit Windowa
Up to 
42 days
3 days
Entry/Safety Assessments/Questionnaire
Informed 
consent/Assentb
X
Demography
Xa
Medical History
Xa
Medication History
X
Inclusion/Exclusion 
Review
X
X
Physical Examinationc
Xa
X
X
X
X
Tanner Stage and 
Testicular Volumed
Xa
X
Heighte
Xa
X
X
Weightf
Xa













Vital Signsg
Xa
X
X
X
X
X
Single ECG
Xa
X
X
Cardiac MRI (or 
Echocardiogram)h
Xa
X
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Year 1
Visit Numbera
Screena
1
2
3
4
5
6
7
8
9
10
11
12
13
Study Weeka
1
5
9
13
17
21
25
29
33
37
41
45
49
Study Daya
1
29
57
85
113
141
169
197
225
253
281
309
337
Visit Windowa
Up to 
42 days
3 days
Clinical Laboratory 
Testsi
Xa
X
X
X
X
Serum Ferritin, Serum 
Iron, TIBC, % 
Transferrin Saturationi
Xa
X
X
X
X
Hormones (LH, FSH, T4, 
TSH, androstenedione, 
testosterone)e
Xa
X
Fecal Occult Bloodj
Xa
X
X
X
X
Clinical Outcomes Assessments (Completed by Caregiver)
PODCI Questionnairek
Xa
X
X
X
C-SSRSL
Xa
X
X
X
X
EQ-5D-3L
Xm
X
X
X
HRU
Xm
X
X
X
ZBI
Xm
X
X
X
WPAI-CG
Xm
X
X
X
Clinical Outcomes Assessments (Completed by Subject)
PODCI Questionnaire
Xm,n
X
X
X
EQ-5D-Y 
Xm
X
X
X
Imaging Assessments
MRI-Liver
Xa
X
X
DXA-Spine
Xa
X
DXA-Whole Body
Xa
X
X-ray (hand and wrist)d
Xa
X
Functional Assessments
Ambulatory Statuso
X












X
PFTs
X
X
X
X
4 Stair Climbp
Xa
X
X
X
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Year 1
Visit Numbera
Screena
1
2
3
4
5
6
7
8
9
10
11
12
13
Study Weeka
1
5
9
13
17
21
25
29
33
37
41
45
49
Study Daya
1
29
57
85
113
141
169
197
225
253
281
309
337
Visit Windowa
Up to 
42 days
3 days
Northstar Ambulatory 
Assessmentp
Xa
X
X
X
Range of Motion
Xa
X
X
X
Strength Assessment 
Xa
X
X
X
PUL
Xa
X
X
X
6MWTp
Xa
X
X
X
Investigational Product Administration
Investigational Product 
administrationq
X
X
X
X
X
X
X
X
X
X
X
X
X
PK/PD, Immunogenicity and Biobanking
PK sampler
Xa
X
X
Immunogenicity
Xa
X
X
Group 1 and Group 2 
Biomarkers
X
X
Infusion Site Reaction 
monitoring
X











X
Adverse event 
monitoring
X











X
Concomitant medication
X











X
Abbreviations: = ongoing/continuous monitoring; 6MWT=Six minute walk test; C-SSRS=Columbia Suicide Severity Rating Scale, DXA=Dual-energy x-ray 
absorptiometry; ECG =electrocardiogram; EQ-5D-3L=EuroQoL 5 Dimensions 3 Levels; EQ-5D-Y=EuroQoL 5 Dimensions - Youth; FSH=Follicle stimulating 
hormone; HRU=Healthcare Resource Utilization; LH=Luteinizing hormone; MRI=magnetic resonance image; PD=Pharmcodynamics; PFTs =pulmonary 
function tests; PK=Pharmocokinetics, PODCI=Pediatric Outcomes Data Collection Instrument; PUL=Performance of Upper Limb, T4=thyroxine; TIBC=Total 
iron binding capacity, TSH=thyroid stimulating hormone; WPAI-CG=Work Productivity and Activity Impairment questionnaire adapted for Caregiving; 
ZBI=Zarit Burden Interview.
a.
Subjects will enroll in the study within 42 days of completion of the Week 97 of the parent study B5161002. If this window is exceeded, the sponsor and 
investigator will assess if the subject may still participate in this OLE study, and which, if any assessments must be completed to confirm eligibility.  If 
needed assessments may be performed on consecutive days within the study visit window. For example where functional assessments and imaging 
assessments are collected at the same visit, subjects can be assessed over a 2 day period. Demography and medical history will be collected from Study 
B5161002.  The following assessments may be collected as screening data from subject's Week 97 visit within Study B5161002.  These include: Physical 
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Year 1
Visit Numbera
Screena
1
2
3
4
5
6
7
8
9
10
11
12
13
Study Weeka
1
5
9
13
17
21
25
29
33
37
41
45
49
Study Daya
1
29
57
85
113
141
169
197
225
253
281
309
337
Visit Windowa
Up to 
42 days
3 days
Examination, Tanner Stage and Testicular Volume, Height, Weight, Vital Signs, Single ECG, Cardiac MRI (or Echocardiogram), Clinical Laboratory Tests, 
GLDH, Serum Ferritin, Serum Iron, TIBC%, Transferrin Saturation, Hormones (LH, FSH, T4, TSH, andostenedione, testosterone), Fecal Occult Blood, 
PODCI, C-SSRS, MRI-Liver (data from Week 93), DXA-Spine, DXA-Whole Body, X-ray (hand and wrist), Functional Assessments (not including 
ambulatory status which is not collected in B5161002), PK, Immunogenicity.
b.
Informed consent must be provided by the subject’s caregiver (parent or legal guardian).  Subject will be required to provide assent in compliance with local 
regulations and IRB/EC requirements.
c.
The physical examination will also include a nose and throat mucosal exam.
d.
Once sexual maturity is reached defined as Tanner Stage V, Tanner stage and Testicular Volume, x-ray (hand and wrist) and hormone testing are no longer 
mandatory.
e.
Height and hormone testing should be performed in the morning.  If a subject is unable to stand safely, an estimated height can be calculated using the 
subject’s ulnar length and the instructions provided in the functional assessment manual.
f.
Weight will be collected at each visit. The weight from the current visit or the previous month’s visit can be used to calculate the appropriate dose by body 
weight.
g.
Vital sign evaluations will include pre-dose supine blood pressure, pulse rate, respiratory rate and temperature.
h.
Cardiac MRI is the preferred method of imaging, If it is not possible to perform cardiac MRI (eg, not available at the site) echocardiogram will be 
acceptable.  The same method of cardiac imaging utilized in B5161002 should be used consistently within a single subject through Study B5161004.
Cardiac MRI with gadolinium should only be performed after all other imaging assessments are completed. 
i.
Clinical laboratory tests include hematology, chemistry, gamma-glutamyl transferase (GGT), glutamate dehydrogenase (GLDH), prothrombin time (PT), 
activated partial thromboplastin time (aPTT), creatine kinase, amylase, and urinalysis.  In Year 1, cardiac troponin I will be collected at Screening, Week 49 
and Early Withdrawal only.
j.
If a Week 97 B5161002 stool sample result is not available at the screening visit, a collection kit and mailing supplies will be sent home and the caregiver 
will be responsible for collection and mailing the sample back to the site.  For all other visits after screening, a stool sample will be collected at home within 
approximately 1 week prior to the scheduled visit.
k.
PODCI Completed by Parent/Caregiver.
l.
For the C-SSRS the “Children’s Since Last Visit” assessment will be performed. This will be completed by the caregiver.
m. The PODCI Adolescent self-report, EQ-5D-Y, EQ-5D-3L, ZBI, and HRU questionnaires are new assessments not included in the parent study B5161002 
and should be collected at screening and all subsequent visits outlined in the Schedule of Activities. If a subject is unwilling to provide self-reported data 
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Year 1
Visit Numbera
Screena
1
2
3
4
5
6
7
8
9
10
11
12
13
Study Weeka
1
5
9
13
17
21
25
29
33
37
41
45
49
Study Daya
1
29
57
85
113
141
169
197
225
253
281
309
337
Visit Windowa
Up to 
42 days
3 days
they can still participate in the study. 
n.
Children will become eligible to complete the Adolescent self-report version of the PODCI when they turn 11 years of age at which time they should be 
asked to complete the PODCI Adolescent self-report version at indicated time points throughout the study.  In addition, caregivers will continue to complete 
the PODCI Parent-report (2-10 years) version throughout the study. If a subject is unwilling to provide self-reported data they can still participate in the 
study.
o.
Ambulatory status will be recorded at the screening visit. Ambulation is defined as the ability to walk unassisted and without braces for at least 10 m. At 
subsequent visits if subject becomes non-ambulatory this should be recorded.
p.
If a loss of ambulation has occurred 4 Stair Climb, Northstar Ambulatory Assessment and 6MWT do not need to be completed. Please record date that 
ambulation was lost.
q.
Investigational product should be delivered in a 2 hour window 30 minutes including the flush time.  If a dosing visit cannot be conducted within the visit 
window, attempts should be made to bring the subject back for dosing as soon as possible; however the dosing must not occur within 2 weeks prior to the 
next scheduled dose.  If the subject cannot return in this timeframe, the dose should be missed and the next visit should be conducted per the Schedule of 
Activities.
r.
PK samples to be taken prior to dosing. 
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Study Flowchart: Year 2, 3 and 4 and Early Withdrawal
Year 2,3,4 and Early Withdrawal
Visit Numbera
14
26,
38
15,
27,
39
16
28,
40
17,
29,
41
18,
30,
42
19,
31,
43
20,
32,
44
21,
33,
45
22,
34,
46
23,
35,
47
24,
36,
48
25,
37, 
49
Early 
Withdrawal
Study Weeka
53,
101, 
149
57, 
105, 
153
61,
109, 
157
65,
113, 
161
69
117, 
165
73,
121, 
169
77, 
125, 
173
81, 
129, 
177
85, 
133, 
181
89,
137, 
185
93, 
141, 
189
97, 
145, 
193
Study Daya
365,
701,
1037
393,
729,
1065
421,
757,
1093
449,
785,
1121
477,
813,
1149
505,
841,
1177
533,
869,
1205
561,
897,
1233
589,
925,
1261
617,
953,
1289
645,
981,
1317
673,
1009,
1345
Visit Window
3 days
Safety Assessments/Questionnaire
Physical Examinationb
X
X
X
X
X
Tanner Stage and Testicular Volumec
X
X
X
Heightd
X
X
X
Weighte
X










X
X
Vital Signsf
X
X
X
X
X
Single ECG
X
X
X
X
X
Cardiac MRI (or Echocardiogram)g
X
X
Clinical Laboratory Testsh
X
X
X
X
X
Serum Ferritin, Serum Iron, TIBC, % Transferrin 
Saturationh
X
X
X
X
X
Hormones (LH, FSH, T4, TSH, androstenedione, 
testosterone)c,d
X
X
X
Fecal Occult Bloodi
X
X
X
X
X
Clinical Outcomes Assessments (Completed by Caregiver)
PODCI Questionnairej
X
X
X
C-SSRSk
X
X
X
X
EQ-5D-3L
X
X
X
HRU
X
X
ZBI
X
X
X
WPAI-CG
X
X
X
Clinical Outcomes Assessments (Completed by Subject)
PODCI QuestionnaireL
X
X
X
X
EQ-5D-Y 
X
X
X
X
Imaging Assessments
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Year 2,3,4 and Early Withdrawal
Visit Numbera
14
26,
38
15,
27,
39
16
28,
40
17,
29,
41
18,
30,
42
19,
31,
43
20,
32,
44
21,
33,
45
22,
34,
46
23,
35,
47
24,
36,
48
25,
37, 
49
Early 
Withdrawal
Study Weeka
53,
101, 
149
57, 
105, 
153
61,
109, 
157
65,
113, 
161
69
117, 
165
73,
121, 
169
77, 
125, 
173
81, 
129, 
177
85, 
133, 
181
89,
137, 
185
93, 
141, 
189
97, 
145, 
193
Study Daya
365,
701,
1037
393,
729,
1065
421,
757,
1093
449,
785,
1121
477,
813,
1149
505,
841,
1177
533,
869,
1205
561,
897,
1233
589,
925,
1261
617,
953,
1289
645,
981,
1317
673,
1009,
1345
Visit Window
3 days
MRI-Liver
X
X
X
DXA-Spine
X
X
DXA-Whole Body
X
X
X-ray (hand and wrist) c
X
X
Functional Assessments
Ambulatory statusm
X










X
X
PFTs
X
X
X
4 Stair Climbn
X
X
X
Northstar Ambulatory Assessmentn
X
X
X
Range of Motion
X
X
X
Strength Assessment 
X
X
X
PUL
X
X
X
6MWTn
X
X
X
Investigational Product Administration
Investigational Product administrationo
X
X
X
X
X
X
X
X
X
X
X
X
PK/Immunogenicity
PK samplep
X
X
X
Immunogenicity
X
X
X
Biobanking Sample (Group 1 and Group 2 Biomarkers)
X
Infusion Site Reaction monitoring
X











X
Adverse event monitoring
X











X
Concomitant medication
X











X
Abbreviations: = ongoing/continuous monitoring; 6MWT=Six minute walk test; C-SSRS=Columbia Suicide Severity Rating Scale, DXA=Dual-energy x-ray 
absorptiometry; ECG = electrocardiogram; EQ-5D-3L=EuroQoL 5 Dimensions 3 Levels; EQ-5D-Y=EuroQoL 5 Dimensions - Youth; FSH= Follicle stimulating 
hormone; HRU=Healthcare Resource Utilization; LH= Luteinizing hormone; MRI=magnetic resonance image; PD=Pharmcodynamics; PFTs = pulmonary 
function tests; PK=Pharmocokinetics, PODCI=Pediatric Outcomes Data Collection Instrument; PUL=Performance of Upper Limb, T4 =thyroxine; TIBC=Total 
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Page 19
Year 2,3,4 and Early Withdrawal
Visit Numbera
14
26,
38
15,
27,
39
16
28,
40
17,
29,
41
18,
30,
42
19,
31,
43
20,
32,
44
21,
33,
45
22,
34,
46
23,
35,
47
24,
36,
48
25,
37, 
49
Early 
Withdrawal
Study Weeka
53,
101, 
149
57, 
105, 
153
61,
109, 
157
65,
113, 
161
69
117, 
165
73,
121, 
169
77, 
125, 
173
81, 
129, 
177
85, 
133, 
181
89,
137, 
185
93, 
141, 
189
97, 
145, 
193
Study Daya
365,
701,
1037
393,
729,
1065
421,
757,
1093
449,
785,
1121
477,
813,
1149
505,
841,
1177
533,
869,
1205
561,
897,
1233
589,
925,
1261
617,
953,
1289
645,
981,
1317
673,
1009,
1345
Visit Window
3 days
iron binding capacity, TSH=thyroid stimulating hormone; WPAI-CG=Work Productivity and Activity Impairment questionnaire adapted for Caregiving; 
ZBI=Zarit Burden Interview.
a.
If needed assessments may be performed on consecutive days within the study visit window. For example where functional assessments and imaging 
assessments are collected at the same visit, subjects can be assessed over a 2 day period.
b.
The physical examination will also include a nose and throat mucosal exam.
c.
Once sexual maturity is reached defined as Tanner Stage V, Tanner stage and Testicular Volume, x-ray (hand and wrist) are no longer mandatory.
d.
Height and hormone testing should be performed in the morning.
e.
Weight will be collected at each visit.  The weight from the current visit or the previous month’s visit can be used to calculate the appropriate dose by body 
weight.
f.
Vital sign evaluations will include pre-dose supine blood pressure, pulse rate, respiratory rate and oral temperature.
g.
Cardiac MRI is the preferred method of imaging. If it is not possible to perform cardiac MRI (eg, not available at the site) echocardiogram will be 
acceptable.  The same method of cardiac imaging utilized in B5161002 should be used consistently within a single subject through Study B5161004.
Cardiac MRI with gadolinium should only be performed after all other imaging assessments are completed
h.
Clinical laboratory tests include hematology, chemistry, gamma-glutamyl transferase (GGT), glutamate dehydrogenase (GLDH), prothrombin time (PT), 
activated partial thromboplastin time (aPTT), creatine kinase, amylase, and urinalysis.  Cardiac troponin I will be collected at Week 97, 145, 193 and Early
Withdrawal.
i.
A stool sample will be collected at home within approximately 1 week prior to the scheduled visit.
j.
PODCI Completed by Parent/Caregiver.
k.
For the C-SSRS the “Children’s Since Last Visit” assessment will be performed. This will be completed by the caregiver.
l.
The PODCI Adolescent self-report if applicable. Children will become eligible to complete the Adolescent self-report version of the PODCI when they turn 
11 years of age at which time they should be asked to complete the PODCI Adolescent self-report version at indicated time points throughout the study.  In 
addition, caregivers will continue to complete the PODCI Parent-report (2-10 years) version throughout the study. If a subject is unwilling to provide self-
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Page 20
Year 2,3,4 and Early Withdrawal
Visit Numbera
14
26,
38
15,
27,
39
16
28,
40
17,
29,
41
18,
30,
42
19,
31,
43
20,
32,
44
21,
33,
45
22,
34,
46
23,
35,
47
24,
36,
48
25,
37, 
49
Early 
Withdrawal
Study Weeka
53,
101, 
149
57, 
105, 
153
61,
109, 
157
65,
113, 
161
69
117, 
165
73,
121, 
169
77, 
125, 
173
81, 
129, 
177
85, 
133, 
181
89,
137, 
185
93, 
141, 
189
97, 
145, 
193
Study Daya
365,
701,
1037
393,
729,
1065
421,
757,
1093
449,
785,
1121
477,
813,
1149
505,
841,
1177
533,
869,
1205
561,
897,
1233
589,
925,
1261
617,
953,
1289
645,
981,
1317
673,
1009,
1345
Visit Window
3 days
reported data they can still participate in the study. 
m. Ambulatory status should be reviewed at each visit. Ambulation is defined as the ability to walk unassisted and without braces for at least 10 m. If a 
subject becomes non-ambulatory this should be recorded in the CRF.
n.
If a loss of ambulation has occurred 4 Stair Climb, Northstar Ambulatory Assessment and 6MWT do not need to be completed. Please record date that 
ambulation was lost.
o.
Investigational product should be delivered in a 2 hour window 15 minutes including the flush time. If a dosing visit cannot be conducted within the visit 
window, attempts should be made to bring the subject back for dosing as soon as possible; however the dosing must not occur within 2 weeks prior to the 
next scheduled dose.  If the subject cannot return in this timeframe, the dose should be missed and the next visit should be conducted per the Schedule of 
Activities.
p.
PK samples to be taken prior to dosing.
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1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06252616 is a humanized monoclonal antibody which binds and neutralizes myostatin, 
also known as growth differentiation factor 8 (GDF-8), a negative regulator of muscle mass.
The proposed indication is the treatment of Duchenne muscular dystrophy (DMD).
Protocol B5161004 is an open-label extension (OLE) to Protocol B5161002 and will provide 
an assessment of the long term safety, efficacy, PD and PK of IV dosing of PF-06252616 in 
boys with DMD.
1.2. Background and Rationale
1.2.1. Myostatin Role in Muscle Regulation
Myostatin or GDF-8 is a member of the transforming growth factor-(TGF) superfamily of 
secreted differentiation factors (McNally, 2004). The role of GDF-8 as a negative regulator 
of muscle fiber growth and mass is well conserved between zebrafish, dogs, cattle, mice and 
humans.  The effect of inhibiting GDF-8 has been best studied in skeletal muscle; knockout
GDF-8 -/- mice possess muscles that are 100% to 200% larger than wild type controls due to 
a combination of muscle fiber hyperplasia and hypertrophy (McPherron et al, 1997). Despite 
having increased skeletal muscle and decreased fat, the GDF-8 knockout mice appear to be 
normal and healthy.  Consistent with its role in mice, genetic loss of myostatin is associated 
with increased muscle mass in many different species (McNally, 2004).  One case of a 
human has been reported with a homozygous mutation of the GDF-8 gene, associated with 
an absence of GDF-8 protein, in which the boy was found to have increased muscle strength 
and, by age 4, no apparent untoward health effects (Schuelke et al, 2004). Pharmacologic 
inhibition of GDF-8 activity in rodents resulted in increased muscle mass and improved 
muscle function in both normal and dystrophic animals (Bradley et al, 2008). Given its 
effect on skeletal muscle and the absence of abnormality in knockout mice, GDF-8 represents 
an attractive target for diseases associated with muscle loss.
1.2.2. Duchenne Muscular Dystrophy
DMD is the most frequently inherited neuromuscular disease, and predominantly affects 
boys.  It is an X-linked muscular dystrophy caused by a mutation at Xp21 in the gene coding 
for the protein dystrophin (Bushby et al, 2010; Manzur et al, 2008) which is absent from the 
muscle of boys with DMD.  DMD is the most severe of all muscular dystrophies and is 
characterized by skeletal and cardiac muscle degeneration.  Boys with DMD are 
phenotypically unremarkable at birth; onset of symptoms usually occurs around two to three 
years of age.  Most boys lose the ability to walk between the ages of 10 and 14 (Lamperti & 
Moggio, 2010). Progressive cardiac problems manifest in the second decade.
There is no approved treatment that can stop or reverse the progression of DMD.  
Glucocorticoid therapy, although not specifically approved for use in DMD, is the only 
pharmacotherapy that has been demonstrated to ameliorate symptoms in patients with DMD, 
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irrespective of underlying mutation, and is currently the standard of care.  Although 
glucocorticoids may improve muscle strength for a period of time and delay the loss of 
ambulation, (Mendell et al, 1989; Bonifati et al, 2000), chronic use is associated with 
well-known adverse events such as weight gain and broad hypothalamic-pituitary-adrenal 
axis effects which eventually lead to the discontinuation of treatment, often in the teenage 
years.
Additional disease management consists primarily of supportive care which ranges from 
physical therapy to maximize function and minimize muscle contractures, to orthotics, 
tendon release surgery (which provides temporary benefit as contractures will redevelop), use 
of wheel chair (usually by age 12), surgical correction of scoliosis and use of respiratory care 
including various forms of assisted ventilation (including tracheotomy).  Respiratory 
infections may be treated with antibiotics.  Death from pneumonia or cardiac involvement in 
late teens or early twenties is commonly observed in these patients (Manzur et al, 2008).
1.2.3. PF-06252616
PF-06252616, also referred to as Anti-Myostatin, is a humanized recombinant antibody 
immunoglobulin G1 (IgG1) that neutralizes GDF-8 (myostatin).  PF-06252616 was 
developed by humanization of a mouse monoclonal antibody, designated mRK35, generated 
by immunizing GDF-8 knockout mice with recombinant GDF-8 and isolating monoclonal 
antibodies by splenic fusion using standard hybridoma methodology.  The substitution of 
specific amino acid residues in the Fc region of PF-06252616 has reduced the effector 
functions of the molecule.  The humanized recombinant antibody has a human kappa 
constant domain and a human IgG1 constant domain with 3 mutations to reduce potential 
effector function.  PF-06252616 investigational drug product is supplied as a lyophilized 
sterile powder in a single use glass vial.  The vials will be reconstituted with sterile water for 
injection (SWFI).  The reconstituted PF-06252616 drug product is clear to slightly opalescent 
and colorless to slightly colored in appearance.
1.3. Clinical Experience with PF-06252616
The clinical program for PF-06252616 was initiated in June 2012 with a Phase 1 first-in-
human (FIH), randomized, double-blind (sponsor and pharmacist unblinded), placebo-
controlled study (B5161001) evaluating the safety, tolerability, pharmacokinetic, 
pharmacodynamic, and pharmacologic (anabolic) effects of escalating single doses of 
PF-06252616 in healthy adult subjects.  The study is complete with 73 subjects enrolled at a 
single site.  Single doses of 1, 3, 10, 20, and 40 mg/kg administered by the intravenous (IV) 
route and 3 mg/kg administered by the subcutaneous route, or placebo were studied.  In 
addition, a repeat IV administration of PF-06252616 10 mg/kg at 2 week intervals over a 28-
day treatment period was investigated.  Safety was demonstrated at all dose levels and there 
were no dose-related trends in frequency of reported treatment-emergent adverse events 
(TEAEs).
The Protocol B5161002 is the first-in-patient (FIP) study with PF-06252616.  This Phase 2 
randomized, 2-period, double blind, placebo-controlled, multiple-ascending dose study aims 
to provide initial clinical assessment of the safety, efficacy, PK, and PD of PF-06252616 
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following repeat IV doses in ambulatory boys with DMD.  Additionally, it aims to 
demonstrate the efficacy of treatment over 3 escalated IV dose levels of PF-06252616 based 
on an observed mean change from baseline on function 4SC as compared to placebo 
following 49 weeks of treatment.  The study is ongoing and plans to enroll approximately 
105 eligible subjects who will be randomly assigned to 1 of 3 sequence groups and receive 
placebo or investigational product PF-06252616 at 3 escalating dose levels of 5 mg/kg IV, 
20 mg/kg IV, and 40 mg/kg IV administered every 4 weeks for approximately 96 weeks 
(2 treatment periods of approximately 48 weeks each).
Complete information for this compound may be found in the Single Reference Safety 
Document (SRSD), which for this study is the Investigator’s Brochure (IB).
1.4. Rationale for Dosage Selection and Method of Administration
The dose for each subject will be based on their individual maximum tolerated dose (MTD) 
up to 40 mg/kg from Study B5161002. This study will use the same route and frequency of 
administration as Study B5161002. IV was chosen as the route of administration for 
B5161002 to support the large dose that will be required to obtain the targeted GDF-8
coverage. The frequency of administration was chosen as 4 weeks to achieve targeted 
GDF-8 coverage but also to reduce the burden on subject travel to study sites.
1.5. Study Design Rationale
This is an OLE of the B5161002 study designed primarily to evaluate the long-term safety of 
PF-06252616 as well as to collect data regarding maintenance of effect up to 4 years.
1.6. Anticipated Risks and Safety Monitoring
Anticipated risks are based on clinical and toxicology data which can be found in the IB.
1.6.1. Hepatic Injury
 
In DMD, serum alanine 
transaminase (ALT) and aspartate transaminase (AST) elevation related to muscle pathology 
is common and well described (McMillan et al, 2011). Therefore the utility of these enzymes 
as markers of hepatocellular injury is limited. Glutamate dehydrogenase (GLDH) has been 
identified as a biomarker of liver injury that is independent of muscle damage.  Using a 
validated assay, GLDH will be evaluated to provide additional information regarding liver 
function.
Abnormal values for serum ALT or AST concurrent with abnormal elevations in total 
bilirubin that meet the criteria for Hy’s law and in the absence of other causes of liver injury 
are considered potential cases of drug-induced liver injury (potential Hy’s law cases) and 
should always be considered important medical events.  Subject data meeting these criteria 
will be referred to the external data monitoring committee (E-DMC) for review. In addition, 
Liver MRI will be obtained according to the Schedule of Activities to monitor for safety by 
CCI
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Final Protocol, 08 April 2016
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quantifying iron accumulation. The E-DMC will include a Hepatic Expert to review any 
cases of potential liver toxicity.
1.6.2. Gastric Erosion and Haemorrhage
 
 Given the use of systemic glucocorticoids in 
the DMD population, there is a risk of increased incidence of gastric erosion and 
haemorrhage.  Study subjects will therefore be asked specifically to report symptoms that 
may be associated with such pathology.  Monitoring of haemoglobin, haematocrit and fecal 
occult blood will be performed.
1.6.3.
 Sexual Development
 
 
  Given the target population of DMD 
pre-pubertal boys, this effect needs to be monitored.  Tanner staging and testicular volume 
will be used to monitor pubertal development, in addition to the measurement of sex 
hormone levels and bone age with a wrist and hand X-ray assessment. Should boys reach 
sexually maturity during the trial as indicated by a Tanner Stage V rating, monitoring will no 
longer be mandatory.
1.6.4. Bone Metabolism
 
 
 
 
 
 is therefore 
appropriate to examine BMD in the DMD population.  
 
effect on BMD – especially in those treated with glucocorticoids – would clearly be 
  DXA will be used to monitor for changes in BMD.
1.6.5. Cardiac
 
  However, based on literature regarding 
the biology of GDF-8 and GDF-11 and their potential modulation of cardiomyocyte and 
cardiac function, combined with the known cardiac dysfunction in the target population of 
DMD boys, it is appropriate to focus on the potential for an interaction between the drug and 
the underlying disease state.  The ongoing Phase 2 Study (B5161002) includes monitoring 
with 12-lead electrocardiogram (ECG) for rhythm or morphological change, cardiac 
Troponin I for cardiac muscle tissue injury, and cardiac MRI with gadolinium (or 
echocardiography if cardiac MRI is not available at the site) to evaluate left ventricular 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
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ejection fraction (LVEF).  Subjects will remain on the same imaging modality to assure 
consistency in safety measure from Study B5161002 through Study B5161004.  Additional 
cardiac parameters (eg, left ventricular wall thickness, cardiac strain, and fibrosis) may be 
collected during cardiac MR imaging for exploratory analyses.  Abnormal values for each of 
these measures have been reported in DMD, even in patients under the age of 10.  In light of 
the variability of findings during the natural history of the disease, no pre-specified stopping 
rules have been defined. Cardiac monitoring will continue in this study as outlined in the 
Schedule of Activities.
1.6.6. Radiation
The possible risks related to subjects undergoing evaluation with DXA and x-ray for bone 
age includes the risk of radiation exposure. The average effective dose of radiation received 
for a single DXA scan or hand x-ray for bone age may vary due to the instrument and the 
subject’s body. Annual assessments include a whole body DXA scan, a DXA spine scan and 
a single x-ray image of the hand and wrist.  The expected annual radiation dose resulting 
from these scans for a subject participating in this study should not exceed 0.15 mSv per 
year.  This is less than 1 month of natural background radiation which is approximately 
0.25 mSv per month (Environment, Health & Safety (EHS) Radiation Risk; Blake et al, 
2006).
1.6.7. Other Risks
Possible risks related to the administration of the study drug and/or as a consequence to 
phlebotomy may include hematoma or bruising.
1.6.8. Other Safety Monitoring
Additional safety monitoring will include the parameters of adverse events (AEs), physical 
examination, vital signs, and clinical laboratory parameters (including urinalysis, 
hematology, gamma-glutamyl transferese [GGT], GLDH, prothrombin time/activated partial 
thromboplastin time [PT/aPTT], creatine kinase, amylase, and chemistry) and Columbia 
Suicide Severity Rating Scale (C-SSRS) (see Clinical Outcomes Assessment manual).  
Laboratory monitoring will also be performed to detect ADA and NAb.
1.7. Summary of Risk Benefit
In view of the initial clinical evidence of safety and the monitorable nature of key nonclinical 
toxicological findings, data support an acceptable risk profile for PF-06252616 in the current 
study and support a favorable benefit-risk profile in the indication of DMD.  Authorities will 
be kept informed of any additional data (eg, results from clinical studies) which may affect 
the assessment of the risk/benefit ratio for PF-06252616.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
2.1.1. Primary Objective
To evaluate the long-term safety of IV dosing of PF-06252616 in boys with DMD.
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2.1.2. Secondary Objectives

To evaluate the long-term efficacy of PF-06252616 using functional assessments and 
strength.

To assess the PK and immunogenicity of PF-06252616.
2.1.3. Exploratory Objectives

To evaluate PD markers that may be informative in demonstrating the pharmacologic 
effect of PF-06252616.

To evaluate the long-term functional health effects of PF-06252616 on Parent-report and 
Adolescent self-report scores on the PODCI.

To assess the long-term effects of PF-06252616 on HRQL and healthcare resource 
utilization (HRU) in boys with DMD.

To evaluate the long-term effects of PF-06252616 on caregiver burden, HRQL and work 
productivity and activity impairment.

To collect exploratory biomarker samples for bio-banking.
2.2. Endpoints
2.2.1. Primary endpoints
2.2.1.1. Safety

Incidence and/or rate of intolerability or dose limiting treatment related AEs following up 
to 4 years of treatment.

Incidence and/or rate, severity and causal relationship of TEAEs and withdrawals due to 
TEAEs following up to 4 years of treatment.

Incidence and magnitude of abnormal laboratory findings (clinical laboratory tests: 
hematology, chemistry, GGT, GLDH, PT, aPTT, creatine kinase, amylase, serum ferritin, 
serum iron, total iron binding capacity (TIBC), % transferrin saturation. Hormones: 
luteinizing hormone [LH], follicle stimulating hormone [FSH], thyroxine [T4], thyroid 
stimulating hormone [TSH]. Fecal occult blood, cardiac Troponin I and urinalysis) 
following up to 4 years of treatment.

Abnormal and clinically relevant changes in liver MRI and physical examinations 
(including nose and throat mucosal exam and Tanner stage and Testicular Volume), 
weight, vitals, electrocardiogram (ECG), LVEF measured by cardiac MRI (or 
echocardiogram), bone mineral density by DXA, x-ray (hand and wrist for bone age 
evaluation) and C-SSRS.
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2.2.2. Secondary endpoints
2.2.2.1. Efficacy

Mean change from baseline following up to 4 years of treatment in the following 
functional assessment tests PFTs (to include FVC, FEV1 and PEFR), 4SC, NSAA, PUL, 
ROM and 6MWD.

Mean change from baseline in muscle strength measured by myometry following up to 
4 years of treatment.
2.2.2.2. PK and Immunogenicity
Trough serum PF-06252616 concentrations for all subjects receiving active drug.

Incidence of ADA and NAb.
2.2.3. Exploratory Endpoints
2.2.3.1. PD
To evaluate change from baseline of Lean Body Mass (LBM) determined via whole body 
DXA after up to 4 years of treatment.
2.2.3.2. Clinical Outcome Assessments

To evaluate the long-term functional health effects of PF-06252616:

Changes from baseline in the Pediatric Outcomes Data Collection Instrument 
(PODCI) Parent-report and Adolescent self-report scores.

Change from baseline in the EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) Health 
Questionnaire.

Change from baseline in the EuroQol 5 Dimensions - Youth (EQ-5D-Y) Health 
Questionnaire.

Change from baseline in Healthcare Resource Utilization (HRU) questionnaire.

Change from baseline in Zarit Burden Interview (ZBI).

Change from baseline in the Work Productivity and Activity Impairment. Questionnaire 
adapted for caregiving (WPAI:CG) in the percent work time missed, percent impairment 
while working, percent overall work impairment, and percent activity impairment due to 
a child’s Duchenne muscular dystrophy.

Pooled or exploratory analyses, if conducted, utilizing the biobanked exploratory 
genomic and biomarker samples will be documented in the statistical analysis plan.
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3. STUDY DESIGN
3.1. Study Overview
This is a Phase 2 OLE to protocol B5161002 and will provide an assessment of the long term 
safety, efficacy, PD and PK of IV dosing of PF-06252616 in boys with DMD.
The individual dose level selected for each subject will be based on the maximum tolerated 
dose (MTD) from the parent study B5161002.  However, dose levels may be adjusted based 
on emerging safety or efficacy data from B5161002.
Subjects will be dosed with one of three PF-06252616 dose levels:

5 mg/kg

20 mg/kg

40 mg/kg
Approximately 105 eligible subjects will be assigned to receive an individualized MTD 
based on their tolerability profile/data from B5161002.  No placebo comparator will be 
assessed. Consenting subjects who complete the B5161002 study will be invited to transition 
directly to the OLE study.  Subjects’ results from the B5161002 study may be used as 
screening data for the current study if the subject is enrolled within 42 days of Week 97 visit
of B5161002, see Schedule of Activities and Assessments for details. If this window is 
exceeded, the sponsor and investigator will assess if the subject may still participate in this 
OLE study, and which, if any, assessments must be completed to confirm eligibility.
3.2. Duration of Study and Subject Participation
The OLE study is planned to be conducted over a period of 4 years.  The end of the study 
will be the last visit of the last subject for purposes of closing out sites, informing the 
institutional review board/ethics committee (IRB/EC), and ceasing to send Council for 
International Organizations of Medical Sciences (CIOMS) reports.
Depending on when subjects begin the OLE study, their participation may be as long as 
4 years.  Subjects may be withdrawn from the OLE study should the parent study, B5161002 
fail to meet its planned study objectives, is terminated early for other reasons (eg, sponsor 
decision) or the drug is commercialized.
Subjects will be administered monthly infusions of study drug as well as completion of safety 
and efficacy assessments as per the Schedule of Activities.
In the case where subjects are traveling from a distance, local overnight accommodation will 
be offered.
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3.3. Planned Number of Subjects
Approximately 105 subjects will participate in multiple centers and countries worldwide.
3.4. Safety Monitoring and the E-DMC
From the time of study initiation through completion of the study, the sponsor will conduct 
routine safety monitoring of the data per the safety review plans.  In addition, the E-DMC 
will periodically review safety data as outlined in Section 3.4.1.
3.4.1. External Data Monitoring Committee (E-DMC)
The E-DMC will include experts in the field of neuromuscular diseases and/or statistics.  
Members of the E-DMC will not be Pfizer employees.  The E-DMC will be responsible for 
ongoing efficacy and safety monitoring and its reviews will include aggregate safety, 
targeted medical events of special interest including liver toxicity, and serious adverse event 
(SAE) data.  Additional ad hoc safety reviews may be performed as described in the E-DMC 
charter.
Following each data review, the E-DMC will provide a recommendation to the sponsor 
management to continue the study, modify the study and then continue (eg, but not limited to 
terminate a dose level, remove the liver MRI or other monitoring assessments), or stop the 
study (eg, due to safety).  The recommendations made by the E-DMC to alter the conduct of 
the study will be forwarded to the sponsor management for final decision.  The sponsor 
management will forward such decisions, which may include summaries of aggregate 
analyses of endpoint events and of safety data that are not endpoints, to regulatory 
authorities, as appropriate.  At any time the E-DMC may indicate that the limit of safety 
and/or tolerability has been reached and that any of the dose levels will be removed from the 
study.
Additional details of the type, timing and responsibilities of the E-DMC will be included in 
the E-DMC charter.
4. SUBJECT SELECTION
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
Subject and caregiver eligibility should be reviewed and documented by an appropriate 
member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
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1. Subjects with Duchenne muscular dystrophy who enrolled and completed through Week 
97 of Study B5161002.
2. Evidence of a personally signed and dated informed consent document (ICD) indicating 
that the subject’s parent or legal guardian/caregiver has been informed of all pertinent 
aspects of the study. Subjects may be required to provide assent in compliance with local 
regulations and IRB requirements.
3. Subjects and their legal guardians/caregivers who are willing and able to comply with 
scheduled visits, treatment plan, laboratory tests, and other study procedures.
4. The following inclusion criteria will be assessed using data from the B5161002 study, 
and if data are unavailable, these assessments must be completed prior to enrollment:
a.
Adequate hepatic function on screening laboratory assessments from the Week 97 
visit.
b. GLDH 20 units/liter (2 x upper limit of normal [ULN]) from the Week 97 visit.
c.
Iron content estimate on the liver MRI within the normal range as determined by R2* 
value (R2*75 Hz at 1.5 T or R2*139 Hz at 3.0 T) from the Week 93 visit.
4.2. Exclusion Criteria
The following exclusion criteria will be assessed using Week 97 data from the B5161002 
study, but if unavailable, these assessments must be completed prior to enrollment:
1. Unwilling or unable (eg, metal implants) to undergo examination with closed MRI. If 
subjects required sedation in the B5161002 study they will be permitted to enroll in the 
OLE. In the event that a subject becomes intolerant to MRI scanning, during the OLE, the 
subject may be separately consented to be administered sedation in order to complete the 
MRI.
2. All male subjects who are able to father children and are sexually active and at risk for 
impregnating a female partner, who are unwilling or unable to use with their female 
partner(s) a highly effective method of contraception consistently and correctly for the 
duration of the active treatment period and through the final study visit.  In addition, all 
sexually active male subjects who are unwilling or unable to prevent potential transfer of 
and exposure to drug through semen to their partners by using a condom consistently and 
correctly, beginning with the first dose of investigational product and continuing through 
the final study visit.
3. Subjects who are investigational 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 related to Pfizer employees directly involved in the 
conduct of the study.
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4. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality 
that may increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
5. Participation in other studies involving investigational drug(s), with the exception of 
B5161002, for a minimum of 30 days or within 5 half-lives (whichever is longer) prior to 
signing the informed consent and/or during study participation.
6. History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein or 
additives of this investigational product (histidine, sucrose, edetic acid 
[ethylenediaminetetraacetic acid], and polysorbate 80).
Note: Results considered by the investigator to be transient and inconsistent with the 
subject’s clinical condition may be repeated once during the screening period for 
confirmation of eligibility.  The reason for repeating the assessment should be documented.
4.3. Enrolment
Subjects will be enrolled into the study provided they have satisfied all eligibility criteria.  In 
order to provide the screening data from Study B5161002 to Study B5161004, and for 
programming to recognize the continuation of the subject, the site will complete an electronic 
case report form (eCRF) where subject numbers are recorded for both the parent Study 
B5161002 and OLE Study B5161004.
4.4. Lifestyle Guidelines
The following guidelines are provided:
4.4.1. Meals and Dietary Restrictions
Subjects should maintain their normal dietary intake throughout the study with the following 
exceptions:

Subjects will be asked to fast for at least 8 hours prior to collection of blood to evaluate 
serum ferritin, serum iron, TIBC and % transferrin saturation.

Subjects should avoid large meals for at least 2 hours prior to the DXA scan. Juice, water 
and small snacks may be permitted.  Subjects should be in a state of euhydration.  No 
calcium supplements should be taken within 24 hours of a DXA scan.

Two days prior to collection of stool sample for fecal occult blood testing, whenever 
possible, subjects should refrain from eating red meat, turnips, horseradish, or 
medications containing aspirin or vitamin C and should consume only small amounts of 
chicken, canned tuna fish, peanuts, popcorn, bran cereal, vegetables and fruit.
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4.4.2. Activity
Subjects should be instructed to continue with routine physical therapy including stretching 
or use of orthoses to prevent or minimize contractures or muscle deformities.
Subjects will be instructed to maintain normal activity levels and avoid activities that are not 
part of their normal daily routine within 24 hours of study visits where imaging or functional 
assessments will be performed.
4.4.3. Contraception
All male subjects who are able to father children and are sexually active and at risk for 
impregnating a female partner, must agree to use with their female partner(s) a highly 
effective method of contraception consistently and correctly for the duration of the active 
treatment period and through the final study visit.  The investigator or his or her designee, in 
consultation with the subject and/or the subject’s legal guardian, will confirm the subject has 
selected the most appropriate method of contraception for the individual subject and his 
partner from the permitted list of contraception methods (see below) and instruct the subject 
in its consistent and correct use. Subjects need to affirm that they meet the criteria for correct 
use of at least 1 of the selected methods of contraception. The investigator or his/her 
designee will discuss the need to use highly effective contraception consistently and correctly 
throughout the study and document such conversation in the subject’s chart.  In addition, the 
investigator or his/her designee will instruct the subject and/or subject’s legal guardian to call 
immediately if the selected birth control method is discontinued or if partner pregnancy is 
known or suspected in the subject’s partner.
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of oral, inserted, injected, implanted or transdermal hormonal methods of 
contraception are allowed provided the subject plans to remain on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, or 
suppository).  For countries where spermicide is not available or condom plus spermicide 
is not accepted as highly effective contraception, this option is not appropriate.
4. Male sterilization with absence of sperm in the postvasectomy ejaculate.
5. Bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
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In addition, all sexually active male subjects must agree to prevent potential transfer of and 
exposure to drug through semen to their partners by using a condom consistently and 
correctly, beginning with the first dose of investigational product and continuing through the 
final study visit.
4.5. Caregiver(s)
The parent or legal guardian of the subject will actively participate as caregiver in this study.  
As caregiver, the parent or legal guardian will not only provide informed consent, but will 
also actively participate in the study procedures, including completing the PODCI Parent-
report (2-10 years) questionnaire and being interviewed for the C-SSRS on behalf of the 
subject. Caregivers will complete the ZBI, EQ-5D-3L, WPAI:CG questionnaires and a 
measure of their child’s HRU electronically on a tablet or similar device. The caregiver will 
communicate observed safety information to the investigator or designee as appropriate.  The 
investigational site will train the caregiver on instructions to collect and/or ship a fecal 
sample, as needed, and provide other instructions on preparing the subject for each study 
visit.
A subject’s caregiver(s) must meet all of the following criteria for the subject to be eligible 
for enrollment in the study:

Is 18 years of age and has demonstrated responsibility as a caregiver through 
monitoring the subject and reporting any observed AEs during the parent B5161002 
study.

Is available to accompany the subject to the clinic visits.

Can follow instructions, including the use of electronic devices for recording subject 
information.

Is willing and able to give written informed consent.
4.6. 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 Sponsor’s Study Web Portal and the 
investigator’s site file.
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, protocol and investigational compound identifiers, subject study numbers, 
contact information for the investigational site, and contact details for a contact center in the 
event that the investigational 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 investigational 
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 investigational 
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site and the study team are not available. It is therefore intended to augment, but not replace, 
the established communication pathways between the investigational 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 investigational site.
4.7. Rater Qualifications
4.7.1. Columbia-Suicide Severity Rating Scale (C-SSRS)
Clinical staff must be trained to complete the C-SSRS.  This training is provided by the 
sponsor and upon completion a certification will be provided to the trained individual. If 
training has already been completed and certified in the B5161002 study this does not need 
to be repeated.
The C-SSRS will be completed with the subject’s caregiver/legal guardian throughout the
study see Section 7.2.7 for further details.
4.7.2. Tanner Stage and Testicular Volume
Tanner staging and testicular volume assessments to evaluate sexual maturation will be 
conducted by a physician, trained physician’s assistant or nurse practitioner as acceptable 
according to local regulation.  Training to conduct the Tanner assessment will be provided by 
the sponsor and upon completion, a certification will be provided to the trained individual. If 
training has already been completed and certified in the B5161002 study, this does not need 
to be repeated.
4.7.3. Clinical Evaluators (CEs)
Functional assessments including the PFTs, 4SC, NSAA, ROM, strength, PUL and 6MWT 
will be conducted by a physiotherapist (or exercise physiologist).  Training on the functional 
assessments and reliability of performance of each assessment specific to this protocol will 
be provided by a master physiotherapist and upon completion, a certification will be provided 
to the individual clinical evaluator.  All CEs who have previously been certified for the 
B5161002 study may not require repeat certification. Details of the assessments, training, 
certification requirements and ongoing quality control are provided in the Functional 
Assessment manual.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonization (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient being tested or used as a reference in a clinical trial, including a product with a 
marketing authorization when used or assembled (formulated or packaged) in a way different 
from the approved form, or when used for an unapproved indication, or when used to gain
further information about an approved use (ICH E6 1.33).
PF-06252616 is incompatible with sodium chloride containing solutions. Therefore, do not 
use Normal Saline (0.9% sodium chloride) or other sodium chloride containing solutions, as 
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a diluent or for flushing the infusion line. Dextrose 5% solution is recommended for use 
during flushing to ensure complete delivery of the prepared dosing solution.
Subjects will be administered PF-06252616 by IV infusion. The investigator site will 
maintain the high level oversight of all subject IV infusions if an alternative infusion location 
is used by the site. Once the investigational product is determined to be tolerated by the 
subject, the investigator and sponsor may explore the possibility of alternative infusion 
locations, as appropriate.  Additional administration instructions will be provided to facilitate 
the infusion of this investigational product at alternative infusion locations.
This is an open-label study. Subjects will receive monthly doses of either, 5 mg/kg, 20 
mg/kg or 40 mg/kg following confirmation of their MTD from the parent study B5161002. 
Dose levels may be adjusted based on emerging safety or efficacy data from B5161002.
Subjects should be administered the investigational product within the visit window 
according to the Schedule of Activities.  If a dosing visit cannot be conducted within the visit 
window, attempts should be made to bring the subject back for dosing as soon as possible; 
however the dosing must not occur within 2 weeks prior to the next scheduled dose.  If the 
subject cannot return for dosing in this timeframe, the dose should be missed and the next 
visit should be conducted per the Schedule of Activities.
Please refer to the dosage and administration instructions in the Investigational Product 
Manual and the Administration Card for complete information on storage, stability, 
preparation and administration of PF-06252616.
5.1. Allocation to Treatment
Allocation of the subject to a dose level will be based on their MTD from the parent study 
B5161002. This dose level will be confirmed by the sponsor at the completion of Study 
B5161002 and entered into the Interactive Response Technology (IRT) System [Interactive 
Web Response (IWR)/Interactive Voice Response (IVR) system] by the sponsor to assure 
proper allocation of subject to corresponding dose level.
Note: The IRT is the source of the subject number.  The IRT system will provide the unique 
subject’s study identification (SSID) number at the end of the first IRT subject transaction.  
This number will be retained throughout the study.
Furthermore, the study site will obtain the container number assignment from the IRT 
system. Once subject screening numbers and container numbers have been assigned, they 
cannot be reassigned.
The dispensing personnel will be required to enter or select information including but not 
limited to their user identification (ID) and password, protocol number, the SSID number and 
the date of birth of the subject.  The dispenser will be provided with the container number 
when drug is being supplied via the IRT.  The IRT system will provide a confirmation report 
containing the subject number and container number assigned.  The confirmation report must 
be retained by the dispenser in the site files.
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There is a 24 hour a day, 365 days a year IRT helpdesk available for any questions or issues.  
The study specific IRT reference manual will provide the contact information and further 
details on the use of the IRT.
5.2. Blinding
This study is open label. Subjects, investigators and pharmacists will be aware of the 
assigned dose level. As this study is planned to be conducted at the same time as parent 
study B5161002, by the same investigators, please refer to the Investigational Product 
Manual which outlines procedures to ensure that the blind is maintained in the parent study.
5.3. Subject Compliance
Study treatment will be administered under the supervision of investigator site personnel.
5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
PF-06252616 will be provided by Pfizer Worldwide Research and Development (PWRD) as 
a lyophilized powder in single use, sterile glass vials.  Each vial will be sealed with a coated 
stopper and an aluminum over-seal and labeled according to local regulatory requirements.  
The drug product must be reconstituted with SWFI for IV infusion.  The reconstituted 
PF-06252616 drug product is a clear to slightly opalescent solution and colorless to slightly 
colored in appearance.
Details of the drug product and its preparation are provided in the dosage and administration 
instructions in the Investigational Product Manual.
PF-06252616 will be packaged as open-label supplies.  The external packaging (carton) will 
describe its contents indicating them as active drug product.  Each carton will contain a 
single vial of study medication, and each carton is identified with a unique container number.  
Each carton will be packaged with a tamper-resistant seal.  The sponsor must be notified of 
any investigational product in which the tamper-resistant seal has been broken and this 
medication should not be used.  Further details will be detailed in the Investigational Product 
Manual.
All ancillary supplies used to prepare and administer doses will be provided by the clinical 
site conducting the study unless otherwise agreed by the sponsor.
5.4.2. Preparation and Dispensing
Investigational product should be prepared and dispensed by appropriately qualified and 
trained personnel (eg, pharmacist, pharmacist technician) as allowed by local, state, and 
institutional guidance.  All dosage and administration calculations as well as dose preparation 
must be performed and checked by a minimum of two (2) clinical site personnel, one of 
whom must be a licensed health care professional.
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Study personnel will receive study specific training on the obligations of the role and will 
sign an agreement that will be maintained in the Site Master File.
Subject’s body weight will be measured at each time point when study drug is administered 
and used to calculate the dose for that visit. After the first dosing visit (Visit 1), the 
subsequent doses may be calculated based on the current visit’s weight or on the prior 
month’s weight.
Under aseptic conditions, PF-06252616 should then be prepared according to the dosage and 
administration instructions in the Investigational Product Manual provided by the sponsor.
5.5. Investigational Product Administration
Following preparation of the study treatment investigational product (PF-06252616) by the 
site personnel (eg, pharmacist or pharmacist technician), the prepared product together with 
the administration card will be provided to the administrator.
Topical anesthetics (eg, topical lidocaine at the site of infusion) may be administered to 
subjects, consistent with institutional guidelines.
The IV infusion should be administered by qualified healthcare professionals trained to 
detect any infusion related issues.  Infusion times, rates, any infusion interruptions or 
infusion rate reduction, will be recorded.  The study drug should be infused over a 2-hour 
period (30 minutes) which includes the flush time.  The time to infuse the investigational 
product with the flush will be recorded.  If a dosing visit cannot be conducted within the visit 
window, attempts should be made to bring the subject back for dosing as soon as possible; 
however the dosing must not occur within 2 weeks prior to the next scheduled dose.  If the 
subject cannot return in this timeframe, the dose should be missed and the next visit should 
be conducted per the Schedule of Activities.
5.5.1. Infusion Reaction
Should subjects experience any infusion site reaction during the IV infusion period, the 
administration should be interrupted and supportive care should be provided according to the 
investigator’s standard of care practice (eg, treatment with an antihistamine).  Treatment 
administration may resume if the reaction resolves.  Following the interruption at the 
discretion of the investigator, the infusion rate may be decreased to half the required rate 
(eg, decreased from 50 mL/hr to 25 mL/hr or the duration may be increased from 2 to
4 hours).  If the infusion rate is decreased, the 2-hour window for delivery will not be 
applied.  The duration of the treatment interruption should not exceed the limits of stability of 
the drug product solution per the dosage and administration instruction in the Investigational 
Product Manual.  Consult the Investigational Product Manual for detailed instructions 
regarding study drug preparation, stability and administration.  No more than 1 treatment 
interruption should occur during any single infusion. If subjects are scheduled to receive 
their glucocorticoids on the same day as study drug administration, the site may instruct 
subjects to take them in the morning prior to infusion.
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Once the product is determined to be tolerated by the subject, the investigator and sponsor 
may explore the possibility of alternative infusion locations, as appropriate.  Additional 
administration instructions will be provided to facilitate the infusion of this investigational 
product at alternative infusion locations.
5.6. Investigational Product Storage
The qualified personnel, (eg, pharmacist, pharmacy technician) will ensure that all 
investigational products are stored in a secured area with controlled access under 
recommended storage conditions and in accordance with applicable regulatory requirements.
Investigational product should be stored in its original container and in accordance with the 
label.
Upon receipt at the study site, the investigational products (PF-06252616) must be stored in a 
2 to 8C temperature-monitored refrigerator and in the original carton, according to labeled 
storage conditions.  The investigational product cannot be used after the expiration date on 
the label.  Please refer to the Investigational Product Manual for complete information on 
storage, handling and stability of the investigational products both prior to and following 
reconstitution. Storage conditions stated in the SRSD which for this study is the IB will be 
superseded by the storage conditions stated in the labeling.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure that ensures active daily evaluation 
for excursions should be available.  The operation of the temperature monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure 
it is maintained in working order.
Any excursions from the product label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to the storage conditions, as 
soon as possible as described in the labeling.  Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the sponsor.
Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product.  
Specific details regarding information the site should report for each excursion will be 
provided to the site.  It will not be considered a protocol deviation if the sponsor approves the 
use of the investigational product after the temperature excursion. Use of the investigational 
product prior to sponsor approval will be considered a protocol deviation.
Receipt of materials, door opening and closing, and other routine handling operations where 
the product(s) are briefly out of labeled temperature range are not considered excursions.
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The Investigational Product Manual should be referenced for any additional guidance on 
storage conditions and actions to be taken when conditions are outside the specified range.
5.7. Investigational Product Accountability
The investigator’s site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product.
5.7.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the study site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
5.8. Concomitant Treatment(s)

Subjects will abstain from all prohibited concomitant medications, except if required for 
treatment of AEs.

All concomitant medications taken during the study will be recorded with the indication 
and start and stop dates of administration.  All subjects will be questioned about 
concomitant medications at each visit.

Medications taken within 28 days prior to Day 1 will be documented as prior medication.  
Medications taken from Day 1 of the current study will be documented as concomitant 
medications.
5.8.1. Permitted Therapies

Subjects will be permitted to receive glucocorticoids (ie, deflazacort, prednisolone, and 
prednisone). During the study the dose regimen should, where possible, remain stable. 
Discontinuation or dose adjustment is permitted if deemed clinically necessary.  If 
subjects are schedule to receive their glucocorticoids on the same day as study drug 
administration, the site may instruct subjects to take them in the morning prior to 
infusion.

Subjects will be permitted to receive ACE inhibitors, blockers, ARB (angiotensin II 
receptor antagonist) or aldosterone blocker/thiazide diuretic; however, subjects must plan 
to remain on a stable dose during the study. Discontinuation or dose adjustment is 
permitted if deemed clinically necessary.

Supplements such as vitamin D, coenzyme Q10, carnitine, aminoacids (glutamine, 
arginine), anti-inflammatory/anti-oxidants (eg, fish oil, vitamin E, green-tea extract) are 
permitted.  Calcium is permitted but should not be taken with 24 hours prior to a DXA 
scan.  A multi-vitamin without iron is permitted.
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
Bisphosphonates are permitted.  If they are to be administered at a study visit where 
imaging is also being performed, they should be administered after the imaging is 
complete.  This will help to mitigate any potential interference they may have on the 
imaging.
5.8.2. Prohibited Therapies
The following are prohibited from the time of signing the informed consent through the final 
study visit.

Immunosuppressant therapy (other than glucocorticoids).

Other investigational therapies.

Exon skipping and nonsense mutation targeted therapies and utrophin.

Aminoglycosides (eg, gentamicin), if required for management of an infection, a short 
course of treatment no longer than 14 days is permitted.

Androgens or human growth hormones current and in the past 3 months.

Multi-vitamin with iron or iron supplements.
At the discretion of the sponsor, subjects who receive prohibited therapies may be terminated 
from the study.
6. STUDY PROCEDURES
Every attempt should be made to schedule the visits on the day specified in the Schedule of 
Activities.
During screening, subjects and caregiver(s) will be assessed for study eligibility.  All 
screening must be completed and reviewed for subject eligibility before the subject is 
enrolled into the study.  Screening tests with results considered by the investigator to be 
transient and inconsistent with the subject’s clinical condition may be repeated once during 
the screening period for confirmation of eligibility.  Imaging based examinations for 
screening must be reviewed for quality by the central imaging vendor before the subject is 
enrolled to assure an adequate baseline image has been acquired.  If the image is determined 
to be of poor quality, it should be repeated.  The visit window for screening is to allow for 
the analysis of laboratory testing, assurance of imaging quality and to provide multiple days 
to perform the assessments.  If needed, assessments should be conducted on consecutive days
within the study window if more than 1 day is required to complete all assessments.  For 
example where functional assessments and imaging assessments are collected at the same 
visit, subjects can be assessed over a 2-day period. Demography and medical history will be 
collected from Study B5161002.
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The majority of screening assessments will come from the Week 97 assessment provided in 
Study B5161002, including Physical Examination, Tanner Stage and Testicular Volume, 
Height, Weight, Vital Signs, Single ECG, Cardiac MRI (or Echocardiogram), Clinical 
Laboratory Tests, GLDH, Serum Ferritin, Serum Iron, TIBC%, Transferrin Saturation, 
Hormones (LH, FSH, T4, TSH, andostendedione, testosterone), Fecal Occult Blood, PODCI, 
C-SSRS, MRI-Liver (data from Week 93), DXA-Spine, DXA-Whole Body, X-ray (hand and 
wrist), Functional Assessments (not including ambulatory status which is not collected in 
B5161002), PK, Immunogenicity.
If a Week 97 B5161002 stool sample result is not available at the screening visit, a collection 
kit and mailing supplies will be sent home and the caregiver will be responsible for collection 
and mailing the sample back to the site.  For all other visits after screening, a stool sample 
will be collected at home up to 1 week prior to the scheduled visit window.
It is important to note that some additional assessments may be required (eg, ambulatory 
status, PFTs to establish study baseline, medication history).  As soon as these assessments 
are completed and a subject’s eligibility has been confirmed, they may be enrolled into the 
study.
The PODCI child self-report (if eligible), EQ-5D-Y, EQ-5D-3L, ZBI, and HRU are new 
assessments not included in the parent study B5161002 and should be collected at screening 
and all subsequent visits outlined in the Schedule of Activities. If a subject is unwilling to 
provide self-reported data they can still participate in the study.
If a subject becomes a screen failure for the current study, they will not be permitted to 
re-screen.
6.1. Informed Consent/Assent
The subject’s parent or legal guardian must sign the informed consent document (ICD) prior 
to initiation of any screening assessments.  The subject will be required to provide assent in 
compliance with local regulations and IRB/EC requirements. Consent should be provided 
prior to conducting the assessments for the Week 97 visit in Study B5161002 to assure that 
there is consent to use these assessments for screening in the current study.
6.2. Procedures
All procedures for the Screening and Study Period should be conducted per the Schedule of 
Activities and Assessments.

Demographics: Information such as date of birth, race, and gender will be collected.

Medical History: Medical history will include confirmation by genetic testing of the 
diagnosis of DMD as obtained as reported from an appropriate regulated laboratory using 
a clinically validated genetic test (genetic testing is not provided by the sponsor).  Results 
must confirm the presence of a mutation in the dystrophin gene(s) which is clinically 
consistent with the diagnosis of DMD.  The mutation type will be reported.
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
Medical history data from B5161002 will be reviewed for any significant medical
histories and concurrent illnesses that required or are requiring specialist consultation or 
treatment.

Medication History: Complete history will include all prescription or non-prescription 
drugs, and dietary and herbal supplements taken within 28 days prior to the planned first 
dose.  Detailed information (dose, regimen) on glucocorticoid steroids will be collected.

Physical Examination: including nose and throat mucosal exam.

Tanner Stage and Testicular volume. If sexual maturity is reached during the study as 
confirmed by an assessment of Tanner Stage V, these assessments are no longer 
mandatory.

Height: Height should be measured in the morning.  If a subject is unable to stand safely, 
an estimated height can calculated using the subject’s ulnar length and the instructions 
provided in the functional assessment manual.

Weight: The body weight is required to calculate the subject’s dose.  After the first 
dosing visit the subsequent doses may be calculated based on the current visit’s weight or 
on the prior month’s weight.

Vital signs: Pre-dose supine blood pressure, pulse rate, respiratory rate, and temperature.

ECG: Single 12-lead ECGs will be obtained.

Cardiac MRI (with or without gadolinium) or Echocardiogram

The modality used to monitor LVEF should be consistent throughout the study for each 
subject and should be the same modality used in Study B5161002, 

If cardiac MRI with gadolinium is used, the imaging may only performed following all 
other imaging at the study visit.

Clinical laboratory testing:

Fasting blood collection: serum ferritin, serum iron, TIBC and % transferrin saturation.

Blood samples for Biomarkers: Group 1 (fasting collection) & Group 2.

Blood samples for hematology, chemistry, GGT, GLDH, PT, aPTT, creatine kinase,
amylase and cardiac troponin I.

Blood sample for hormones (LH, FSH, T4, TSH, androstenedione, testosterone).  Blood 
collection for hormones should be done in the morning. If Tanner stage V is reached 
these samples are no longer mandatory.
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
Blood sample for immunogenicity.

Urine sample for urinalysis.

Blood Sample for PK: Will be collected prior to dosing.

Fecal occult blood: Fecal sample is to be collected at home up to 1 week prior to 
scheduled visit window.

Clinical Outcomes Assessments (COA)

PODCI: This questionnaire will be completed by the caregiver and if possible a self-
report will be completed by the subject at the same visit (subject must be 11 years or 
older to complete). If a subject is unwilling to provide self-reported data, they can still 
participate in the study.

C-SSRS: Children’s Since Last Visit (Version 6/23/10) will be completed with the 
caregiver.

EQ-5D: The EQ-5D-3L will be completed by the caregiver and if possible the EQ-5D-
Youth will be completed by the subject at the same visit.  These are new assessments 
introduced in this study and should be completed at screening and subsequent visits 
outlined in the Schedule of Activities.  If a subject is unwilling to provide self-reported 
data can still participate in the study.

HRU questionnaire: This assessment will be completed by the caregiver. This is a new 
assessment introduced in this study and should be completed at screening and subsequent 
visits outlined in the Schedule of Activities.

ZBI: This assessment will be completed by the caregiver. This is a new assessment 
introduced in this study and should be completed at screening and subsequent visits 
outlined in the Schedule of Activities.

WPAI:CG: This assessment will be completed by the caregiver. This is a new 
assessment introduced in this study and should be completed at screening and subsequent 
visits outlined in the Schedule of Activities.

Magnetic resonance imaging (MRI): liver. Baseline/screening data will be obtained 
from Week 93 in the B5161002 study.

Fasting Dual-energy x-ray absorptiometry (DXA): whole body and spine.

X-ray: non-dominant hand and wrist. The same hand imaged in the B5161002 study 
should be imaged in the B5161004 study. If Tanner stage V is reached during the study 
these assessments are no longer mandatory.
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
Ambulatory Status:  Ambulatory status will be collected at screening and as an 
unscheduled procedure if there should be a change from the screening assessment during 
the study.  Ambulation is defined as the ability to walk unassisted and without braces for 
at least 10 m.

Functional assessments: 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. All functional assessments should be completed in 
the following order, PFTs, 4SC, NSAA, ROM, Strength, PUL, 6MWT. If loss of 
ambulation occurs, the 4SC, NSAA and 6MWT will not be completed.
6.3. Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 
reasons, or the inability of the subject/caregiver to comply with the protocol-required 
schedule of study visits or procedures at a given study site. Subjects may be withdrawn from 
the OLE study should the parent study, B5161002 fail to meet its planned study objectives, is 
terminated early for other reasons (eg, sponsor decision) or the drug is commercialized. 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 records.  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject to return for a final visit, if 
applicable, and follow-up with the subject regarding any unresolved AEs.
If the subject withdraws from the study and also withdraws consent 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.
In the event of clinically important treatment-emergent suicidal ideation or suicidal behavior, 
the subject will be withdrawn from the study and will receive the appropriate medical care.  
The Investigator will follow up until the subject’s condition has stabilized.  Additionally, a 
risk assessment or evaluation of suicide risk will be completed by a child and adolescent 
mental health provider as part of the psychiatric evaluation and assessment of subject safety.  
Refer to Section 7.2.7.
Clinically important suicidality includes but is not limited to:
a.
Suicidal behavior (with or without intent of suicide or serious self-harm).
b. Determination of “yes” on question 4 (Active Suicidal Ideation with Some Intent or Act, 
Without Specific Plan) for the Suicidal Ideation section of the C-SSRS.
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c.
Determination of “yes” on question 5 (Active Suicidal Ideation with Specific Plan and 
Intent) for the Suicidal Ideation section of the C-SSRS.
d. Determination of “yes” on the question of Actual Attempt, Interrupted Attempt, Aborted 
Attempt, or Preparatory Acts or Behavior for Suicidal Behavior section of C-SSRS.
e.
Acute suicidality to such a degree that precaution against suicide must be exercised.
At the time of withdrawal, procedures outlined in the early withdrawal visit should be 
performed as detailed in the Schedule of Activities and Assessments.
6.4. 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.  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 permissible local 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
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test.  In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject.  When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible.  The 
study team will be informed of these incidents in a timely fashion.
Consistent with the institutional guidelines, a topical anesthetic (eg, topical lidocaine) may be 
administered to subjects prior to the blood draw.
7.1. Blood Volume
The total blood volume per month will not exceed approximately 40 mL.
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The following chart provides estimates of the approximate blood volume collected by visit.
Period 
Visit
Total Volume (mL) At Each 
Visit
Year 1
Screening
40
Week 13
10
Week 25
14
Week 37
10
Week 49
40
All other visits (9 additional 
visits)
10*
Total Volume Year 1
204
Year 2-4
Week 61, 109, 157
10
Week 73, 121, 169
22
Week 85, 133, 181
10
Week 97, 145, 193
40
All other visits (9 additional visits 
per year)
10*
Total Volume Year 2, 3, 4
172
Early Withdrawal
30
*Standard hematology/chemistry and routine safety bloods as required.
7.2. Safety
7.2.1. Clinical Laboratory
The following safety laboratory tests will be performed at times defined in the Schedule of 
Activities section of this protocol.  Unscheduled clinical labs may be obtained at any time 
during the study to assess any perceived safety concerns.
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Laboratory Tests
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
Platelet count
WBC count (and 
morphology as 
applicable)
Total neutrophils 
(Abs)
Absolute 
neutrophils (ANC)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes 
(Abs)
BUN
Creatinine
Glucose 
Calcium
Sodium
Potassium
Chloride
Total 
CO2 (Bicarbonate)
AST, ALT
Total Bilirubin
Alkaline 
phosphatase
Uric acid
Albumin
Total protein
Serum Phosphorus
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte 
esterase
Microscopya
GGT
GLDH
PT
INR
aPTT
Creatine kinase
Amylase
Cardiac Troponin I
Serum Ferritinc
Serum Ironc
Total Iron Bindingc
Capacity (TIBC)c
Unsaturated Binding
capacityc,
% Transferrin 
Saturationc
Hormones (LH, FSH, 
T4 (total and free),
TSH, androstenedione, 
testosterone) d
Fecal Occult
Blood
Additional Testsb
AST, ALT (repeat)
Total bilirubin 
(repeat)
Albumin (repeat)
Alkaline 
phosphatase 
(repeat)
Direct bilirubin
Indirect bilirubin
Creatine kinase
GGT
GLDH
PT
INR
a. Only if urine is positive for blood, protein, nitrites or leukocyte esterase.
b. Additional testing for potential Hy’s Law cases only.
c. Following an 8 hour overnight fast.
d. Collect blood in the morning for hormone testing.
7.2.2. Physical Examinations/Nose and Throat Exam
Physical examinations may be conducted by a physician, trained physician’s assistant, or 
nurse practitioner as acceptable according to local regulation.  The physical examination will 
include head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, 
gastrointestinal, musculoskeletal, and neurological systems.  A targeted nose and throat 
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mucosal exam will be performed according to the Schedule of Activities to monitor for any 
signs of mucosal telangiectasias. If the examination status is abnormal, the investigator will 
be asked to determine whether the abnormality is “clinically significant”, and if so, document 
as an AE.
7.2.3. Tanner Stage and Testicular Volume
Tanner Staging will be performed according to the Schedule of Activities to monitor for 
signs of accelerated sexual development. The physical changes in pubertal development 
(genital and pubic hair growth) will be assessed using the system described by Marshall and 
Tanner (1970). In addition to the Tanner staging, a measurement of testicular size (volume) 
using orchidometer beads will be documented. If a subject reaches a Tanner Stage V during 
the conduct of the study, further Tanner Staging, Testicular Volume, hormone testing and 
x-rays will no longer be mandatory.
7.2.4. Vitals
Supine blood pressure, pulse rate, respiratory rate and temperature will be measured at times 
specified in Schedule of Activities section of this protocol.  Unscheduled collection times 
will be permitted, as necessary, to ensure appropriate collection of safety data.
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.
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.
7.2.5. Electrocardiogram (ECG)
ECGs should be collected at times specified in the Schedule of Activities section of this 
protocol.
All scheduled ECGs should be performed after the subject has rested quietly for at least 
10 minutes in a supine position.
Single 12-lead ECGs will be obtained; the average of the triplicate ECG measurements 
collected at Week 97 from Study B5161002, will serve as each subject’s time-controlled 
baseline QTc value.
The QTc interval should be recorded using the QTcF (QTc Fridericia) value in milliseconds.  
In the event that the equipment is not able to provide the QTcF, the formula below will be 
used to calculate.
Formula = QT/((60/HR)^(1/3))
To ensure safety of the subjects, a qualified individual at the investigator site will make 
comparisons to baseline measurements.  If the QTcF interval is increased by 45 msec from 
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the baseline, or an absolute QTcF value is 500 msec for any scheduled ECG, then 
2 additional ECGs will be collected, approximately 2-4 minutes apart, to confirm the original 
measurement.
If the average of QTcF values from the triplicate measurements remains above the threshold
value (45 msec from the baseline; or is 500 msec), then a single ECG must be repeated at 
least hourly until QTcF values from 2 successive ECGs fall below the threshold value that 
triggered the repeat measurement.
If QTcF values remain 500 msec (or 45 msec from the baseline) for greater than 4 hours 
(or sooner at the discretion of the investigator); or QTcF intervals get progressively longer, 
the subject should undergo continuous ECG monitoring.  A cardiologist should be consulted 
if QTcF intervals do not return to less than 500 msec (or to <45 msec above the baseline) 
after 8 hours of monitoring (or sooner at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads are placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read 
QTcF value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified physician’s interpretation determines that the QTcF values are in the acceptable 
range.
7.2.6. Cardiac MRI/Echocardiogram
Cardiac MRI or echocardiograms should be collected at times specified in the Schedule of 
Activities section of this protocol.  The same method of cardiac imaging should be used 
consistently within a single subject and it should be the same method used in Study 
B5161002.
Cardiac MRI with gadolinium is the preferred method for cardiac imaging.  When cardiac 
MRI with gadolinium is used, it should only be collected after all imaging required at the 
same visit is performed.  If the subject has a contraindication to gadolinium, cardiac MRI 
without gadolinium will be acceptable.  Cardiac MRIs will be read by a central imaging 
vendor and only the results of LVEF will be provided to sites.  Sites will be provided with a 
scanning and image transmittal guide for collection of the cardiac MRI.
If it is not possible to perform cardiac MRI (eg, it is not available at the site), echocardiogram 
will be acceptable.  Echocardiogram will be read locally at each site.  To ensure safety of the 
subjects, a qualified individual at the investigator site will evaluate the echocardiogram for
parameters such as left arterial 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. Echocardiogram should be performed using a 2-D imaging collection method.
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7.2.7. Assessment of Suicidal Ideation and Behavior –Columbia Suicide Severity Rating 
Scale (C-SSRS)
C-SSRS: The C-SSRS will be evaluated at times specified in the Schedule of Activities. 
The Children’s Since Last Visit (Version 6/23/10) of the C-SSRS should be utilized for all 
visits in B5161004.  The Since Last Visit version refers to the subject’s experience since their 
last visit (see Clinical Outcomes Assessment manual).
Given the sensitive nature of the subject matter of this assessment, the C-SSRS will be 
conducted with the subject’s caregiver/legal guardian on the subject’s behalf throughout the 
study, rather than administering this evaluation directly with the study subjects.
If at any visit the subject endorses a 4 or 5 on the C-SSRS ideation section or reports any 
suicidality behavior, then an evaluation of suicide risk (risk assessment) must be completed 
and the subject must be discontinued. Subject Withdrawal and evaluation of suicide risk 
(risk assessment) must be completed.
Risk Assessment: In the event that a subject endorses a 4 or 5 on the C-SSRS ideation 
section or reports any suicidality behavior, an evaluation of suicide risk (risk assessment) will 
be completed as part of the psychiatric evaluation and assessment of subject safety to 
participate will be performed by the following child and adolescent mental health provide: In 
the United States: 1) Child and Adolescent Psychiatrists (board certified or board eligible), 
2) psychiatrist who have training and experience in the diagnosis and treatment of psychiatric 
disorders in the pediatric population, or 2) Psy. D. or Ph.D. level Clinical Psychologists
licensed Master’s level Clinical Social Workers (MSW) or licensed psychiatric Nurse 
Practitioners (PNP) who have training and experience in the diagnosis and treatment of 
psychiatric disorders in the pediatric population.
Written documentation of the risk assessment should be included in the subject’s source 
documentation and the risk assessment CRF will be completed.  The risk assessment CRF 
serves as further verification that the psychiatric evaluation and assessment of subject safety 
have been completed for all subjects endorsing items 4 or 5 on the C-SSRS ideation section 
or reporting suicidal behavior.
7.3. Banked Biospecimens
7.3.1. Markers of Drug Response
Studying the variation in genetic markers and other biomarkers may help to explain some of 
the variability in response seen with some drugs among different individuals.  This is referred 
to as pharmacogenomics/biomarker research.  Comparing the deoxyribonucleic acid (DNA), 
ribonucleic acid (RNA), protein, and metabolite variation patterns of subjects who respond 
well and those who respond poorly to treatment may help to better define the most 
appropriate group of patients in which to target a given treatment.  Collecting biospecimens 
for exploratory pharmacogenomics/biomarker analyses and retaining them in the Pfizer 
BioBank makes it possible to better understand the drug’s mechanism of action and to seek 
explanations for differences in, for example, exposure, efficacy, tolerability, or safety not 
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anticipated prior to the beginning of the study.  Providing these biospecimens is a required 
study activity for study sites and subjects, unless prohibited as such by local regulations or 
ethics committee decision.
To protect subjects’ confidentiality, the banked biospecimens and data generated from them 
will be coded with the SSID number.  Samples will be kept in a facility accessible only by 
swiping a badge.  Data will be stored on password-protected computer systems.  The key 
between the code and the subject’s personal identifiers will be held at the study site; the 
researchers using the biospecimens and data generated from them will not have access to the 
key nor any personally identifying information.  Biospecimens will be used only for the 
purposes described here and in the ICD/subject information sheet; any other uses require 
additional ethical approval.  Unless a time limitation is required by local regulations or 
ethical requirements, biospecimens will be stored indefinitely to allow for future research on 
the topics described here, including research conducted during the lengthy drug development 
process and also postmarketing research.  Subjects can withdraw their consent for the use of 
their biospecimens at any time by making a request to the investigator, in which event any 
remaining biospecimen will be destroyed; data already generated from the biospecimens will 
continue to be stored to protect the integrity of existing analyses.  It is very unlikely that 
results generated from the biospecimens will have any clinical, diagnostic, or therapeutic 
implications for the individual study participants.  Subjects are notified in the ICD/subject
information sheet that their results will not be given to them, unless required by local laws or 
regulations, in which case results will be returned via the investigator.  Results will not be 
provided to family members or other physicians, nor will they be recorded in the subject’s 
medical record.  There is no intention to contact subjects after completion of the clinical 
study.
Biomarkers in Group 1 will be collected in the morning following an 8 hour fast to be 
retained for exploratory analyses in this study include the following:
Biomarker Group 1- Collect annually beginning at screening in current study:

Prep B1.5 (K2 EDTA plasma collection optimized for 
biomarker/proteomic/metabonomic analysis): A 2 mL blood biospecimen will be 
collected.

Prep B2.5 (serum collection optimized for biomarker/ proteomics/metabonomic 
analysis): A 2.5 mL blood biospecimen will be collected.
Biomarker Group 2- Collect annually beginning at screening in current study:

Prep R1 (PAXGene whole blood collection optimized for RNA analysis): A 2.5 mL
blood biospecimen will be collected.

Prep P4 (Cell-free RNA): A 10 mL blood biospecimen will be collected.
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The banked biospecimens will be collected from all subjects unless prohibited by local 
regulations or ethics committee decision.  Detailed collection, processing, storage, and 
shipment instructions are provided in the central laboratory manual.
It is possible that the use of these biospecimens may result in commercially viable products.  
Subjects will be advised in the ICD/subject information sheet that they will not be 
compensated in this event.
7.3.2. Additional Research
Unless prohibited by local regulations or ethics committee decision, subjects will be asked to 
indicate on the consent form whether they will allow the banked biospecimens to also be 
used for the following research:

Investigations of the disease under study in the clinical study, and related conditions.

Biospecimens may be used as controls.  This includes use in case-control studies of 
diseases for which Pfizer is researching drug therapies; use in characterizing the natural 
variation among people in genes, RNA, proteins, and metabolites; and use in developing 
new technologies related to pharmacogenomics/biomarkers. 
Subjects need not provide additional biospecimens for the uses described in this section; the 
biospecimen specified in the Markers of Drug Response section will be used.  Subjects may 
still participate in the clinical study if they elect not to allow their banked biospecimens to be 
used for the additional purposes described in this section.
7.4. Pharmacokinetics (Serum for Analysis of PF-06252616)
Blood samples (2 mL) to provide serum for pharmacokinetic analysis will be collected into 
the appropriately labeled tubes (containing no anticoagulant or gel separator) at times 
specified in the Schedule of Activities section of the protocol.
All efforts will be made to obtain the pharmacokinetic samples during the pre-dose period as 
described in the Schedule of Activities.
Detailed collection, processing, storage, and shipment instructions are provided in the central 
laboratory manual.
Samples will be analyzed using validated analytical methods in compliance with Pfizer 
standard operating procedures.
7.5. Anti-Drug Antibody (ADA) anti-PF-06252616 and Neutralizing Antibody (NAb)
Blood samples (2 mL) to provide serum for analysis of anti-PF-06252616 will be collected 
into the appropriately labeled tubes (containing no anticoagulant or gel separator) at times 
specified in the Schedule of Activities section of the protocol.
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All efforts will be made to obtain the samples during the pre-dose period as described in the 
Schedule of Activities.
Detailed collection, processing, storage, and shipment instructions are provided in the central 
laboratory manual.
Samples will be analyzed using validated analytical methods in compliance with Pfizer 
standard operating procedures.  All samples that are positive in a screening assay will be 
confirmed for antibody specificity and further characterized for titer.  Samples that are 
determined to be positive for ADA may be further tested for the presence of NAb.
7.6. PK and Immunogenicity Sample Shipment
The PK and immunogenicity samples must be processed and shipped as indicated to maintain 
sample integrity.  Any deviations from the PK sample processing steps, including any actions 
taken, must be documented and reported to the sponsor.  On a case-by-case basis, the sponsor 
may make a determination as to whether sample integrity has been compromised.  Any 
sample deemed outside of established stability, or of questionable integrity, will be 
considered a protocol deviation.
As part of understanding the pharmacokinetics or immunogenicity of the study drug, samples 
may be used for further characterization and/or evaluation of the bioanalytical method.  
These data will be used for internal exploratory purposes and will not be included in the 
clinical report.  Samples collected for this purpose will be retained in accordance to local 
regulations and if not used within this timeframe, will be destroyed.
7.7. Imaging Assessments
7.7.1. Liver MRI
Liver MRI will be obtained according to the Schedule of Activities to monitor for safety by 
quantifying iron accumulation.  The standard procedure to obtain serial liver MRIs will be 
described in an Image Acquisition manual which will be provided to the site.  The site will be 
trained on all aspects of obtaining quality liver MRIs.  MRIs will be sent to an independent 
central radiology imaging facility for calculation of the average R2* value which will be used 
to monitor for iron accumulation in the liver.  MRIs must meet the accepted standards of 
quality as described in the Image Acquisition manual and/or Imaging Charter or the site may 
be asked to repeat the liver MRI.
7.7.2. Dual-energy X-ray Absorptiometry (DXA) and X-ray
7.7.2.1. DXA
DXA scans will be obtained according to the Schedule of Activities to measure the percent 
change in lean body mass (LBM) over time and to evaluate bone mineral density (BMD) on 
the spine and whole body without head.  The standard procedure to obtain serial DXA whole 
body and spine scans will be described in an Image Acquisition manual which will be 
provided to the site.  The site will be trained on all aspects of obtaining a quality whole body 
and spine scans.  Scans will be sent to an independent central radiology imaging facility for 
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analysis of the study endpoints.  The independent central reviewer will be blinded to the
study treatment assignment.
Screening DXA should meet the accepted standards of quality as described in the Image 
Acquisition manual and/or Imaging Charter or the site may be asked to repeat it.  Ideally, 
whole body scans will be taken at approximately the same time of day (morning) and 
subjects should avoid large meals for at least 2 hours prior to the scan. Juice, water and a 
small snack may be permitted.  Subjects should be in a state of euhydration.  Food may affect 
the LBM measure.  Calcium should be avoided for 24 hours as it may not absorb and will 
affect the measure of BMD and LBM.
7.7.2.2. X-ray
X-rays of the hand and wrist for bone age assessment will be obtained according to the 
Schedule of Activities.  The standard procedure to obtain serial hand/wrist X-rays will be 
described in an Image Acquisition manual which will be provided to the site. X-ray images 
will only be acquired of the non-dominant hand/wrist and this should be the same hand/wrist 
selected for the B5161002 study.  The site will be trained on all aspects of obtaining a 
hand/wrist X-ray.  X-rays will be sent to an independent central radiology imaging facility 
for bone age analysis.  The independent central radiologist will be blinded to the study 
treatment assignment and the subject’s chronological age.  The ratio of the bone age to the 
chronologic will be provided to the sites by the sponsor.  The hand/wrist X-ray will no longer 
be mandatory if, during the study, the subject is assessed as having reached sexual maturity 
defined as Tanner stage V.
7.7.2.3. Radiation Exposure
The average effective dose of radiation received for a single DXA scan or hand x-ray for 
bone age may vary due to the instrument and the subject’s body.  Annual assessments include 
a whole body DXA scan, a DXA spine scan and a single x-ray image of the hand and wrist.  
The expected annual radiation dose resulting from these scans for a subject participating in 
this study should not exceed 0.15 mSv per year.  This is less than 1 month of natural 
background radiation which is approximately 0.25 mSv per month (EHS Radiation Risk; 
Blake et al, 2006).
7.8. Functional Assessments
Functional assessments will be obtained according to the Schedule of Activities. If 
functional assessments are to be performed on the same day as the investigational product 
administration, they should be performed prior to the IP administration. If the subject is 
defined as non-ambulatory then certain functional assessments can be omitted, as outlined in 
the Schedule of Activities. If possible the date that the subject was defined as non-
ambulatory should be recorded.  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 and in the morning.  The order for completing all testing 
will be detailed in a functional assessment manual.
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All functional assessments will be conducted by a trained physiotherapist (or exercise 
physiologist).  Throughout the study they will be referred to as “Clinical Evaluators (CEs)”.  
Training and reliability confirmation to conduct functional assessments specific to this 
protocol 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 prior to conducting any functional assessments.
In order to assure ongoing quality of the CE abilities to perform functional assessments, 
videotaping may 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.  
The videos will be stored at the site and retained per the record retention requirements.
The training requirements and ongoing quality control will be provided in the Functional 
Assessment manual.
7.8.1. Pulmonary Function Tests (PFTs)
Spirometry will be performed as outlined in the Functional Assessment manual based on 
American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force: 
standardization of lung function testing guidelines 2005 (Miller et al, 2005). 
The FVC, FEV1 will be recorded as absolute volumes in liters and in terms of predicted 
values (Hankinson, 1999 or equivalent) according to age, height, race and gender.  The best
(largest) FVC, and FEV1 measurement from the set of 3 will be captured on the database.  
Note that the best measurement for FVC, FEV1 may occur on different efforts.
PEFR will be performed to produce 3 technically adequate results. The highest PEFR should 
be recorded in L/min.
7.8.2. 4 Stair Climb (4SC)
The 4 SC quantifies in seconds the time required for a subject to ascend 4 standard steps.  
The method the subject uses (eg, using the hand rails) to climb the stairs is recorded to 
understand any change in technique that occurs over time; however at no time is the subject 
instructed on the preferred method (with or without the use of hand rails) used to perform this 
test.
Subjects will also be assessed on the time to descend 4 stairs.  The methods used to descend
4 stairs will also be recorded. This test can be omitted if a subject is considered non-
ambulatory.
7.8.3. Northstar Ambulatory Assessment (NSAA)
The NSAA is a 17-item test that grades performance of various functional skills from 
0 (unable to perform), 1 (completes independently but with modifications), and 2 (complete 
without compensation) (Mazzone et al. 2009). The NSAA also includes 2 timed functional 
tests: rise from floor and run 10 meters. The NSAA has been found to correlate with the 
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6MWT and other functional outcomes in boys with DMD (Mazzone et al, 2010). This test 
can be omitted if a subject is considered non-ambulatory.
7.8.4. Range of Motion (ROM)
Range of motion of the ankle will be evaluated by using goniometry to record any 
occurrences of ankle contractures. This test can be omitted if a subject is considered non-
ambulatory.
7.8.5. Strength Assessment
Muscle strength will be quantified by means of a handheld dynamometer.  The following 
muscle groups will be evaluated: knee extension, elbow flexion, elbow extension and 
shoulder abduction.
7.8.6. Performance of Upper Limb (PUL)
The PUL scale has been devised to assess motor performance of the upper limb for 
individuals with dystrophinopathies (Becker and Duchenne muscular dystrophy).  The 
purpose of an upper limb scale for use in dystrophinopathy is to assess change that occurs in 
motor performance of the upper limb over a prolonged period beginning when a boy is 
ambulant and continuing to the time he loses all arm function when non-ambulant.  Motor 
performance will be impacted by muscle strength, contactures and maturational development 
(puberty), and the scale aims to incorporate performance of shoulder, elbow, wrist and hand 
function.
7.8.7. Six Minute Walk Test (6MWT)
The 6MWT, originally developed for cardiac and respiratory insufficiency, has been revised 
for use in DMD subjects to account for the age and unique characteristics of this population 
(McDonald et al, 2010). The purpose of the test is to evaluate ambulation capacity (distance) 
by endurance of walking for six minutes.  This test has been widely used in natural history 
and therapeutic studies with DMD.  A sizeable variability in the range of 6 minute walk 
distance (6MWD) change at one-year (from -23 to -59 m) as well as a large standard 
deviation (SD) around the mean change (SD 81 to 90 m) were observed in all studies 
(Mazzone et al, 2013; Goemans et al, 2013; McDonald et al, 2013a; McDonald et al, 2013b).  
This test can be omitted if a subject is considered non-ambulatory.
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7.9. Triggered Requirements 
Condition/ Criteria 
Action
Moderate Iron overload/ If the liver iron content 
estimate as determined by R2* value is above the “mild 
overload” threshold (R2* >190 Hz at 1.5 T or R2* 
>369 Hz at 3.0 T
The subject should be referred to a haematologist 
for further assessment
Cardiomyopathy/ If the LVEF falls below 50% on the 
cardiac MRI or echocardiogram at any follow-up visit
The subject should be referred to a cardiologist for 
further assessment.
Spine compression or fracture/ If either the bone 
mineral density increases >4% from the start of Period, 
or if there is a suspicion of a vertebral fracture upon 
central review of the DXA exam
The subject should have a local spine x-ray 
performed to confirm the presence or absences of 
compression or fracture
7.10. Infusion Site Monitoring
From the initiation of the IV infusion, subjects will be monitored for signs of any infusion 
site reactions including but not limited to erythema, swelling, bruising, pain or prutitis.
7.11. Clinical Outcome Assessments (Caregiver completed) 
It is the intent to have all caregiver questionnaires complete electronically on a tablet or
similar hand-held device for convenience of the patient and accurate data capture. However, 
if the license should in anyway prohibit use, an alternate delivery will be explored such as 
use of a paper version. If a suitable alternative is not found a questionnaire may be 
withdrawn from the protocol.
7.11.1. Pediatric Outcomes Data Collection Instrument (PODCI)
In order to evaluate 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 (Daltroy et al, 1998; http://www.aaos.org/).  The pediatric 
version intended for completion by parents or caregivers of children aged 10 years or 
younger will be utilized in this study.  The instrument contains 86 items and 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 summary total score is also computed.  These 
scores range from 0-100 with lower scores representing higher levels of disability.  Scores 
may be reported as standardized, or they may be converted to normative scores based on the 
scores reported in a large, healthy population (see Clinical Outcomes Assessment manual).
7.11.2. Zarit Burden Inventory (ZBI)
The Zarit Burden Interview will be used to assess caregiver burden.  The ZBI originated as a 
29-item questionnaire (Zarit et al, 1985; Zarit et al, 1980) but the revised version which 
contains 22 items will be used in this study. Each item on the interview is a statement which 
the caregiver is asked to endorse using a 5-point scale. Response options range from 0 
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(Never) to 4 (Nearly Always).  A total score is obtained and higher scores indicate a greater 
level of caregiver burden associated with caring for a child with Duchenne muscular 
dystrophy (see Clinical Outcomes Assessment manual). The term “your relative” has been 
substituted with the term “your child”.
7.11.3. EuroQoL 5 Dimensions 3 Levels (EQ-5D-3L)
The EQ-5D Health Questionnaire is a self-completion standardized instrument for use as a 
measure of health outcome (http://www.euroqol.org/about-eq-5d.html).  It consists of a 
descriptive system (EQ-5D) of health-related quality of life states, consisting of five 
dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of 
which can take one of three responses.  The responses record three levels of severity (no 
problems/some or moderate problems/extreme problems) within a particular ED-5D 
dimension.  Additionally, the EQ-5D consists of a standard vertical 20cm visual analogue 
scale (EQ VAS) for recording an individual’s rating for their current health state (see Clinical 
Outcomes Assessment manual).
7.11.4. Work Productivity and Activity Impairment Questionnaire adapted for 
Caregiving (WPAI:CG)
The WPAI:CG is a self-reported measure of work productivity and impairment 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.
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.
Each score is expressed as a percentage (0-100%) with higher scores indicating greater 
impairment and less productivity.
In this study, the WPAI:CG will measure the effect of a child/adolescent’s Duchenne 
muscular dystrophy on a caregiver’s work productivity and regular activities.
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7.11.5. Healthcare Resource Utilization (HRU) questionnaire
The Healthcare Resource Use 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).
7.12. Clinical Outcome Assessments (Subject completed)  
It is the intent to have all subject questionnaires completed electronically on a tablet or
similar hand-held device for convenience of the patient and accurate data capture. However, 
if the license should in anyway prohibit use, an alternate delivery will be explored such as 
use of a paper version. If a suitable alternative is not found a questionnaire may be 
withdrawn from the protocol.
If a subject is unwilling to provide self-reported data, they can still participate in the study.
7.12.1. Pediatric Outcomes Data Collection Instrument (PODCI)
Children will become eligible to complete the Adolescent self-report version of the PODCI 
questionnaire once they are 11 years of age.  The PODCI is a patient-reported assessment of 
musculoskeletal health intended for use in children and adolescents (Daltroy et al, 1998; 
http://www.aaos.org/).  The instrument contains 83 items and 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 summary total score is also computed.  These scores 
range from 0-100 with lower scores representing higher levels of disability.  Scores may be 
reported as standardized, or they may be converted to normative scores based on the scores 
reported in a large, healthy population (see Clinical Outcomes Assessment manual).
7.12.2. EuroQol 5 Dimensions - Youth
The EQ-5D-Y is a newly developed generic instrument measuring health-related quality of 
life in children and adolescents 8 years onwards. It was adapted from the EQ-5D original 
questionnaire (http://www.euroqol.org/about-eq-5d.html). It consists of a descriptive system 
(EQ-5D) of health-related quality of life states, consisting of five dimensions including 
mobility (walking about), self-care (looking after myself), usual activities (doing usual 
activities), pain/discomfort (having pain or discomfort), and anxiety/depression (feeling 
worried, sad or unhappy) each of which can take one of three responses. The responses 
record three levels of severity (no problems, some problems, or a lot of problems) within a 
particular ED-5D dimension. Additionally, the EQ-5D consists of a standard vertical 20 cm 
visual analogue scale (EQ VAS) for recording an individual’s rating of their current 
health-related quality of life state on a scale from 0 to 100 with 0 representing the worst and 
100 the best health state he or she can imagine. All items refer to the health state “today.”  
Health state utilities will also be calculated (see Clinical Outcomes Assessment manual).
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8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections.
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a 
serious adverse event (SAE) requiring immediate notification to Pfizer or its designated 
representative.  For all AEs, sufficient information should be obtained by the investigator to 
determine the causality of the AE.  The investigator is required to assess causality.  
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the subject provides informed consent, which is obtained prior to the subject’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 84 calendar days after the last 
administration of the investigational product.  SAEs occurring to a subject after the active 
reporting period has ended should be reported to the sponsor if the investigator becomes 
aware of them; at a minimum, all SAEs that the investigator believes have at least a 
reasonable possibility of being related to investigational product are to be reported to the 
sponsor.
AEs (serious and non-serious) should be recorded on the case report form (CRF) from the 
time the subject has taken at least 1 dose of investigational product through the subject’s last 
visit.
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to:

Abnormal test findings.

Clinically significant symptoms and signs.
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
Changes in physical examination findings.

Hypersensitivity.

Progression/worsening of underlying disease.

Drug abuse.

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose.

Drug withdrawal.

Drug misuse.

Drug interactions.

Extravasation.

Exposure during pregnancy (EDP).

Medication error.

Occupational exposure.
8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong subject, at the wrong time, or at the wrong dosage strength.  
Such medication errors occurring to a study participant are to be captured on the medication 
error CRF, which is a specific version of the AE page, and on the SAE form when 
appropriate.  In the event of medication dosing error, the sponsor should be notified 
immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the investigational product.

Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the participating subject.
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Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the AE page 
and, if applicable, any associated AE(s) are captured on an AE CRF page.
8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows:

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; and/or

Test result leads to a change in study dosing (outside of protocol-stipulated dose 
adjustments) or discontinuation from the study, significant additional concomitant drug 
treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.6. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose 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 event 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 AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
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8.6.1. Protocol-Specified Serious Adverse Events
Unless the investigator believes that there is a causal relationship between the investigational 
product and an event specified below, these events should not be reported by the investigator 
as SAEs as described in the Serious Adverse Event Reporting Requirements section of this 
protocol.  These events are anticipated to occur commonly in a population with DMD.  
However, these events should still be captured as AEs in the CRF.
Protocol-specified events that will not normally be reported in an expedited manner:
a.
Loss of mobility or ambulation.
b. Muscle weakness.
c.
Symptoms related to spinal deformity.
d. Respiratory muscle weakness/Hypoxia.
e.
Fracture.
f.
Steroid related metabolic changes (Hypertension, diabetes).
Should an aggregate analysis indicate that these pre-specified events occur more frequently 
than expected based on the expectation of frequency of the event(s) in question in the 
population for comparison, eg, based on epidemiologial data, literature, or other data,  then 
this will be submitted and reported in accordance with Pfizer’s safety reporting requirements.  
Aggregate analysis of safety data will be performed on a regular basis per internal standard 
operating procedures and on a quarterly basis by the E-DMC.
8.6.2. Potential Cases of Drug-Induced Liver Injury
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s law cases) and should always be considered 
important medical events.
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions. Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of normal 
(× ULN) concurrent with a total bilirubin value 2 × ULN with no evidence of hemolysis 
and an alkaline phosphatase value 2 × ULN or not available.
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
For subjects with preexisting ALT OR AST OR total bilirubin values above the ULN, 
the following threshold values should be used in the definition mentioned above:

For subjects with preexisting AST or ALT baseline values above the normal range:
AST or ALT values 2 times the baseline values and 3 × ULN, or 8 × ULN 
(whichever is smaller).
Concurrent with:

For subjects with preexisting values of total bilirubin above the normal range: Total 
bilirubin level increased from baseline by an amount of at least 1 × ULN or if the 
value reaches 3 × ULN (whichever is smaller).
The subject should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.
In addition to repeating measurements of AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, GGT, GLDH, PT/INR, 
and alkaline phosphatase.  A detailed history, including relevant information, such as review 
of ethanol, acetaminophen, recreational drug and supplement consumption, family history, 
occupational exposure, sexual history, travel history, history of contact with a jaundiced 
person, surgery, blood transfusion, history of liver or allergic disease, and work exposure, 
should be collected.  Further testing for acute hepatitis A, B, or C infection and liver imaging
(eg, biliary tract) may be warranted. All cases confirmed on repeat testing as meeting the 
laboratory criteria defined above, with no other cause for liver function test (LFT)
abnormalities identified at the time, should be considered potential Hy’s law cases 
irrespective of availability of all the results of the investigations performed to determine 
etiology of the abnormal LFTs.  Such potential Hy’s law cases should be reported as SAEs.
8.7. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit should be assessed for medical 
importance.
Hospitalization does not include the following:

Rehabilitation facilities.

Hospice facilities.
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
Respite care (eg, caregiver relief).

Skilled nursing facilities.

Nursing homes.

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the development 
of a new AE or with a worsening of the preexisting condition (eg, for workup of 
persistent pretreatment laboratory abnormality).

Social admission (eg, subject has no place to sleep).

Administrative admission (eg, for yearly physical examination).

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol).

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery).

Hospitalization for observation without a medical AE.

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE.
8.8. Severity Assessment
If required on the AE CRFs, the investigator will use the adjectives MILD, MODERATE, 
or SEVERE to describe the maximum intensity of the AE.  For purposes of consistency, 
these intensity grades are defined as follows:
MILD
Does not interfere with subject’s usual function.
MODERATE
Interferes to some extent with subject’s usual function.
SEVERE
Interferes significantly with subject’s usual function.
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Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject’s usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.9. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious); the investigator must record the causal relationship in the CRF, as appropriate, and 
report such an assessment in accordance with the SAE reporting requirements if applicable.  
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that the investigational product caused or contributed to an AE; 
generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor (see the section on Reporting Requirements).  If the 
investigator’s causality assessment is “unknown but not related to investigational product,”
this should be clearly documented on study records.
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
8.10. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product.
2. An example of environmental exposure would be a case involving direct contact with a 
Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has been 
exposed to chemotherapeutic products).
3. A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy.
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on an SAE report form and an EDP supplemental 
form, regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
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subject reports that she is pregnant and has been exposed to a cytotoxic product by inhalation 
or spillage) using the EDP supplemental form.  This must be done irrespective of whether an 
AE has occurred and within 24 hours of awareness of the exposure.  The information 
submitted should include the anticipated date of delivery (see below for information related 
to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up 
to the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless preprocedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.

Additional information about pregnancy outcomes that are reported as SAEs follows:

Spontaneous abortion includes miscarriage and missed abortion.

Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs.  In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the investigational product.
Additional information regarding the EDP may be requested by the investigator.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the study subject with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.11. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a subject enrolled in the study, 
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the information is not reported on a CRF; however, a copy of the completed SAE report form 
is maintained in the investigator site file.
8.12. Withdrawal Due to Adverse Events (See Also the Section on Subject Withdrawal)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page.
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.13. Eliciting Adverse Event Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject/parent(s)/legal guardian/legally acceptable representative. In addition, each 
study subject/parent(s)/legal guardian/legally acceptable representative will be questioned 
about AEs.
8.14. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
8.14.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event.
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information.  This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of EDP, exposure via breastfeeding, and 
occupational exposure cases.
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE 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 
medications, vaccines, and/or illnesses, must be provided.  In the case of a subject death, a 
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summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative.
8.14.2. Nonserious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF. It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE 
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
Due to the open-label design of the study, statistical analyses will be exploratory in nature. 
The data that will define the baseline for each analysis set will be outlined in the SAP.
9.1. Sample Size Determination
As the number of subjects in this study is limited by the sample size of B5161002 study 
which has approximately 105 subjects, the sample size will be capped at the number of 
enrolled subjects from the parent study. 
9.2. Safety Analysis
Summary statistics will be performed on the following safety endpoints:

Incidence and/or rate of intolerability or dose limiting treatment related AEs.

Incidence and/or rate, severity and causal relationship of TEAEs and withdrawals due to 
TEAEs.

Incidence and magnitude of abnormal laboratory findings (clinical laboratory tests: 
hematology, chemistry, GGT, GLDH, PT, aPTT, creatine kinase, amylase, serum ferritin, 
serum iron, total iron binding capacity (TIBC), % transferrin saturation. Hormone: 
[luteinizing hormone [LH], follicle stimulating  hormone [FSH], thyroxine [T4], thyroid 
stimulating hormone [TSH], fecal occult blood, cardiac troponin I and urinalysis).

Abnormal and clinically relevant changes in liver MRI and physical examinations 
(including nose and throat mucosal exam and Tanner stage/testicular volume), weight, 
vitals, electrocardiogram (ECG), cardiac MRI (or echocardiogram) measured LVEF, 
bone mineral density by DXA, x-ray (hand and wrist for bone age evaluation) and C-
SSRS.
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9.3. Efficacy Analysis
9.3.1. Analysis of efficacy and PD endpoints
Baseline values, change from baseline to last visit in PFTs, 4SC, NSAA, PUL, 6MWD,
muscle strength by myometry and lean body mass by DXA will be described based on 
summary statistics including minimum, median, mean, maximum, and standard deviation. 
Change from baseline may also be assessed for any or all intermediate visits.
9.3.2. Analysis of PK and Immunogenicity

Summary statistics will be provided for trough serum concentrations by dose.

Incidence of ADA and NAb.
9.4. Exploratory Analyses 
9.4.1. Clinical Outcome Assessments
Summary statistics will be presented for the following endpoints by baseline, treatment and 
time point as applicable.  Methodology for any treatment group comparisons will be 
specified in the SAP.

Change from baseline in the PODCI Parent-report and Adolescent self-report scores.

Change from Baseline in the EuroQol 5 Dimension 3 Levels (EQ-5D-3L) Health 
Questionnaire.

Change from Baseline the EuroQoL 5 Dimensions – Youth.

Change from Baseline in the Healthcare Resource Utilization (HRU) questionnaire.

Change from Baseline in the Zarit Burden Interview (ZBI).

Change from Baseline in the Work Productivity and Activity Impairment Questionnaire 
adapted for Caregiving (WPAI:CG) the percent work time missed, percent impairment 
while working, percent overall work impairment, and percent activity impairment due to 
a child’s Duchenne muscular dystrophy.
9.5. Interim Analysis
There is no interim analysis planned for this study.
9.6. Data Monitoring Committee
This study will use an E-DMC.
The E-DMC will be responsible for ongoing monitoring of the safety of subjects in the study 
according to the charter. The recommendations made by the E-DMC in regards to safety or 
interim efficacy to alter the conduct of the study will be forwarded to the sponsor 
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management for final decision. Pfizer will forward such decisions, which may include 
summaries of aggregate analyses of endpoint events and of safety data that are not endpoints, 
to regulatory authorities, as appropriate. Details of the composition of the E-DMC and 
sponsor management including interactions between them will be further specified in the 
DMC charter.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during 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 study site may be subject to review 
by the institutional review board (IRB)/ethics committee (EC), and/or to 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 
or its agents to prepare the study site for the inspection and will allow Pfizer or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly 
provide copies of the inspection findings to Pfizer or its agent.  Before response 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/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.
It should be noted that PODCI and Caregiver burden questionnaires will likely not be 
captured in the CRF but be completed on a tablet or similar hand held electronic device.  
Otherwise, 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 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 
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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’s or the physician’s subject chart.  In 
these cases, data collected on the CRFs must match the data in those charts.
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigative site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
11.2. Record Retention
To enable evaluations and/or 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, and 
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 ICH guidelines, according to local 
regulations, or as specified in the clinical study agreement (CSA), whichever is longer.
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 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 
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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 legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 1996 & 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by a numerical code based on a 
numbering system provided by Pfizer in order to de-identify study subjects.  The study 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 subjects’ personal data consistent 
with applicable privacy laws.
The informed consent/assent documents 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 must be 
reviewed and approved by the sponsor, approved by the IRB/EC before use, and available for 
inspection.
The investigator must ensure that each study subject or his legally acceptable representative, 
or parent(s) or legal guardian, is fully informed about the nature and objectives of the study 
and possible risks associated with participation.
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 he/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 
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consent (eg, minor, decisionally impaired adult), how the investigator determined that the 
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.
12.4. Subject Recruitment
Subject recruitment efforts are not required for this study because this is an extension study.
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application 
in the Member State.  Poor recruitment (recruiting less than the anticipated number in the 
CTA) by a Member State is not a reason for premature termination but is considered a 
normal conclusion to the study in that Member State.
13.2. End of Trial in All Other Participating Countries 
End of trial in all other participating countries is defined as last subject last visit (LSLV).
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14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of
PF-06252616 at any time.
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) within 24 hours.  As directed by Pfizer, all study 
materials must be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies conducted in patients that evaluate the safety and/or efficacy of a Pfizer 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are submitted for posting within 1 year of the primary completion date for studies in 
adult populations or within 6 months of the primary completion date for studies in pediatric 
populations.
Primary completion date is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical study concluded according to the prespecified protocol or was 
terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the primary completion date for studies in adult populations or 
within 6 months of the primary completion date for studies in pediatric populations.
www.pfizer.com
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Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or generated 
by principal investigator, 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 they are 
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 study sites, and that any subsequent publications by the 
principal investigator 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.
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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16. REFERENCES
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deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve 2000; 
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Bradley L. Yaworsky PJ, Walsh FS. Myostatin as a therapeutic target for musculoskeletal 
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dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet 
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Daltroy LH, Liang MH, Fossel AH, et al. The POSNA Pediatric Musculoskeletal Functional 
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Mazzone ES, Messina S, Vasco G, et al. Reliability of the North Star Ambulatory 
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walk test and timed items in ambulant boys with Duchenne muscular dystrophy. 
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Mazzone ES, Pane M, Sormani MP, et al. 24 month longitudinal data in ambulant boys with 
Duchenne muscular dystrophy. PloS One 2013; 8(1):e52512.
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McNally EM.  Powerful genes – myostatin regulation of human muscle mass. New England 
Journal of Medicine 2004; 350(26):2642-4.
McDonald CM, Henricson EK, Han JJ, et al. The 6-minute walk test in Duchenne/Becker 
muscular dystrophy: longitudinal observations. Muscle Nerve 2010; 42(6):966-74.
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 2013a; 48(3):343-56.
McDonald CM, Henricson EK, Abresch RT, et al. The 6-minute walk test and other clinical 
endpoints in Duchenne muscular dystrophy: reliability, concurrent validity, and minimal 
clinically important differences from a multicenter study. Muscle Nerve 2013b; 48(3):357-
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McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new 
TGF-beta superfamily member. Nature 1997; 387(6628):83-90.
Mendell JR, Moxley RT, Griggs RC, et al. Randomized, double-blind six-month trial of 
prednisone in Duchenne’s muscular dystrophy. N Engl J Med.1989; 320(24):1592-7.
Miller MR, Hankinson J, Brusasco V, et al. ATS/ERS Task Force: Standardisation of Lung 
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Appendix 1. Abbreviations
This is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
4SC
four stair climb
6MWD
6 minute walk distance
6MWT
6 minute walk test
ADA
anti-drug antibodies
AE
adverse event
ALT
alanine transaminase
aPTT
activated partial thromboplastin time
AST
aspartate transaminase
ATS/ERS
American Thoracic Society/European Respiratory Society
BMD
bone mineral density
CTA
clinical trial application
CE
Clinical Evaluators
CIOMS
Council for International Organizations of Medical Sciences
COA
Clinical Outcome Assessments
CRF
case report form
CSA
clinical study agreement
C-SSRS
Columbia Suicide Severity Rating Scale
DMD
Duchenne muscular dystrophy
DNA
deoxyribonucleic acid
DXA
dual energy x-ray absorptiometry
EC
ethics committee
ECG
Electrocardiogram
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EDTA
edetic acid (ethylenediaminetetraacetic acid)
EQ-5D-3L
EuroQoL 5 Dimensions 3 Levels
EQ-5D-Y
EuroQoL 5 Dimensions – Youth
EudraCT
European Clinical Trials Database
FEV1
forced expiratory volume in one second
FIH
first in human
FIP
first in patient
FSH
follicle stimulating hormone
FVC
forced vital capacity
GCP
Good Clinical Practice
GDF-8
growth differentiation factor 8
GGT
gamma-glutamyl transferase
GLDH
glutamate dehydrogenase
HRQL
Health-related quality of life
HRU
Healthcare resource utilization
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Abbreviation
Term
IB
investigator’s brochure
ICD
informed consent document
ICH
International Conference on Harmonization
ID
Identification
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IRB
institutional review board
IRT
interactive response technology
IUD
intrauterine device
IV
Intravenous
IVR
interactive voice response
IWR
interactive web response
LBM
lean body mass
LVEF
Left ventricular ejection fraction
LH
luteinizing hormone
LSLV
last subject last visit 
MRI
magnetic resonance imaging
MSW
Master’s level Clinical Social Workers
MTD
maximum tolerated dose
N/A
not applicable
NAb
neutralizing antibodies
NSAA
Northstar Ambulatory Assessment
OLE
open-label extension
PEFR
peak expiratory flow rate
PFTs
pulmonary function tests
PD
Pharmacodynamics
PK
Pharmacokinetic
PNP
psychiatric Nurse Practitioners
PODCI
Pediatric Outcomes Data Collection Instrument
PT
prothrombin time
pQCT
peripheral quantitative computed tomography
PUL
Performance of Upper Limb
PWRD
Pfizer Worldwide Research and Development
RBC
red blood cell
RNA
ribonucleic acid
ROM
range of motion
SAE
serious adverse event
SAP
statistical analysis plan
SOP
standard operating procedure
SRSD
single reference safety document
SSID
single subject’s identification
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Abbreviation
Term
SWFI
sterile water for injection
T4
Thyroxine
TEAEs
treatment emergent AEs
TGF
Transforming growth factor beta
TIBC
total iron binding capacity
TSH
thyroid stimulating hormone
ULN
upper limit of normal
US
United States
WPAI:CG
Work Productivity and Activity Impairment questionnaire adapted 
for Caregiving
ZBI
Zarit Burden Interview
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