Clinical trial NCT03675126
Conditions: Muscular Dystrophy, Duchenne
Keywords: Duchenne muscular dystrophy Exon Skipping DMD Exon 51 Ambulatory Pediatric Nonambulatory Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) Duchenne
Sponsor: Sarepta Therapeutics, Inc.
Start date: 2018-12-19; Completion date: 2021-08-25
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this extension study is to evaluate the safety, tolerability, and pharmacokinetics of repeat administrations of SRP-5051 (vesleteplirsen) in participants with Duchenne muscular dystrophy (DMD) who participated in studies of SRP-5051.

Detailed description:

Arms: arm 1: Participants will receive SRP-5051 via intravenous (IV) infusion. Dosage and frequency will be determined from the safety profile of other ongoing SRP-5051 studies.
Interventions: intervention 1: SRP-5051
Intervention descriptions: intervention 1: SRP-5051 administered as an IV infusion.

Protocol documents:
Prot_000.pdf: 
Protocol 
5051-102, Version 5.0 (Amendment 4) 
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CLINICAL STUDY PROTOCOL 
DRUG: 
SRP-5051 
STUDY NUMBER: 
5051-102 
STUDY TITLE: 
An Open-Label Extension Study for Patients with 
Duchenne Muscular Dystrophy Who Participated in 
Studies of SRP-5051 
IND Number:  
 
EudraCT Number: 
Not applicable 
SPONSOR: 
Sarepta Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 USA 
Phone: +1-617-274-4000 
CURRENT VERSION DATE: 
Version 5.0 (Amendment 4), 21 April 2020
REPLACES VERSION DATE: 
Version 4.0 (Amendment 3), 15 April 2019 
CONFIDENTIALITY STATEMENT 
The information contained in this document is the property of the Sponsor and is confidential. This 
information may not be disclosed, reproduced, or distributed to anyone other than personnel directly 
involved in the conduct of the study and in response to a relevant Institutional Review Board/ 
Independent Ethics Committee and review by a regulatory authority, as required by the applicable laws 
and regulations, without the written authorization of the Sponsor, except to the extent necessary to obtain 
informed consent from those individuals to whom the study drug may be administered. These restrictions 
will continue to apply after the study has closed. 
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INVESTIGATOR’S AGREEMENT 
I have read the Study 5051-102 protocol (Version 5.0 [Amendment 4]) and agree to conduct the 
study as outlined. I agree to maintain the confidentiality of all information received or developed 
in connection with this protocol. 
 
 
 
 
Printed Name of Investigator 
 
 
 
Signature of Investigator 
 
 
 
Date (DD-MMM-YYYY) 
 


 
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1. 
SYNOPSIS 
NAME OF COMPANY 
Sarepta Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 USA 
Phone: +1-617-274-4000 
NAME OF FINISHED PRODUCT 
SRP-5051 Injection 
 
NAME OF ACTIVE INGREDIENT 
SRP-5051 
TITLE: An Open-Label Extension Study for Patients with Duchenne Muscular Dystrophy Who 
Participated in Studies of SRP-5051 
Study Number: 5051-102 
Phase of Study: Phase 1/2 
INVESTIGATOR STUDY SITES: This is a multinational clinical trial to be conducted at 
approximately 100 study sites. 
OBJECTIVES AND CRITERIA FOR EVALUATION: 
Primary Objective 
• 
To evaluate the adverse event (AE) profile of repeat every-4-week (Q4W) administration  
of SRP-5051 
Secondary Objectives 
• 
To determine the pharmacokinetics (PK) of SRP-5051 following repeat  
Q4W administration  
• 
To evaluate additional safety and tolerability of repeat Q4W administration of SRP-5051 
Primary Endpoint 
• 
Incidence of AEs 
Secondary Endpoints 
• 
Plasma concentrations determined at predose, the maximum observed drug concentration 
(Cmax), and 4 to 6 hours after the end of the infusion 
• 
Frequency of clinically relevant abnormalities, as assessed by vital sign measurements, 
physical examination findings, clinical laboratory tests, and ECGs 
 
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NAME OF COMPANY 
Sarepta Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 USA 
Phone: +1-617-274-4000 
NAME OF FINISHED PRODUCT 
SRP-5051 Injection 
NAME OF ACTIVE INGREDIENT 
SRP-5051 
METHODOLOGY: 
This is a Phase 1/2 open-label, long-term extension (LTE) study for DMD patients who have completed 
other studies administering SRP-5051. Each patient will complete 3 periods in this study: Screening, 
Treatment and Observation, and Safety Follow-up. 
Screening Period 
Patients who have completed other studies administering SRP-5051 are eligible to participate in this 
LTE study. For patients who elect to participate in this trial, informed consent is to be obtained at or 
immediately following the End of Study (EOS) visit in the original study administering SRP-5051. 
Patients who do not provide consent at the original study’s EOS visit will have 
 
 that visit to elect to participate in and provide informed consent for this trial.  
Every effort will be made to ensure that patients will not experience any interruption in dosing of  
SRP-5051 during the transition from the original study administering SRP-5051 to this LTE study. 
Treatment and Observation Period 
Patients who enroll in this study will receive their first Q4W dose of SRP-5051 on Day 1 of the 
Treatment and Observation Period.  
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NAME OF COMPANY 
Sarepta Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 USA 
Phone: +1-617-274-4000 
NAME OF FINISHED PRODUCT 
SRP-5051 Injection 
 
NAME OF ACTIVE INGREDIENT 
SRP-5051 
While it is expected that patients will receive their Q4W infusions of SRP-5051 at a designated study 
site (ie, study clinic), home infusions may be an option for dosing visits if circumstances impact a 
patient’s ability to travel by any applicable means (including air travel, personal vehicle travel, car 
service, wheelchair van, etc.). Prior approval from the Sponsor Medical Monitor is required for any 
home infusion visit.  
Initially, patients will be administered the highest dose determined by a Safety Review Committee 
(SRC) or Independent Data Monitoring Committee (IDMC) to be safe and tolerable, as justified in other 
relevant studies of SRP-5051 in accordance with the procedure defined in the relevant study protocol  
or Charter. The final dose confirmation is to be made by the SRC for this LTE study. The 5051-102 
SRC may make the recommendation to proceed to a higher dose level as per the guidance provided in 
the SRC Charter.  
Upon determination of higher dose(s) deemed safe and tolerable in other relevant studies of  
SRP-5051—and only upon receipt of a formal letter from the Sponsor—dose escalation for all patients 
enrolled in this LTE study may proceed to the highest dose determined by the 5051-102 SRC to be safe 
and tolerable, beginning at each patient’s next scheduled dosing visit. Data and recommendations from 
other studies of SRP-5051 will be provided to the 5051-102 SRC to inform the dose-escalation decision.  
Patients will continue SRP-5051 dosing Q4W.  
Vital sign measurements; physical examination findings; clinical laboratory tests; renal biomarkers; 
electrocardiograms (ECGs); 
 
 
 
 changes in concomitant 
medications and/or procedures; and AEs will all be assessed during scheduled visits (Table 1).  
Clinical laboratory tests will also be collected beginning approximately 
 after initial dosing and 
after each subsequent dose. Refer to the Schedule of Events in Table 1. 
 
 
  
 
Safety Follow-up Period 
Clinical laboratory tests, changes in concomitant medications and/or procedures, and AEs will be 
collected 
 after the patient’s last dose of SRP-5051. 
 after completing the Treatment and Observation Period, patients will be asked to complete 
the EOS visit. 
 vital sign measurements, 
physical examination findings, clinical laboratory tests, renal biomarkers, ECGs, changes in 
concomitant medications and/or procedures, and AEs will be assessed at the EOS visit.   
Patients who have received at least 1 dose of study drug and are withdrawn from treatment will be asked 
to complete an Early Termination visit (to complete the EOS assessments) approximately 
  
 after their last dose of SRP-5051, or within 
 of a withdrawal decision if early 
termination occurs after a missed dose.  
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NAME OF COMPANY 
Sarepta Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 USA 
Phone: +1-617-274-4000 
NAME OF FINISHED PRODUCT 
SRP-5051 Injection 
 
NAME OF ACTIVE INGREDIENT 
SRP-5051 
Any AEs are to be recorded through the EOS/Early Termination visit. 
 
  
Patients withdrawn from treatment will not be replaced. 
DURATION OF STUDY: 
Screening Period: Up to 4 weeks (28 days) 
Treatment and Observation Period: Approximately 144 weeks 
Safety Follow-up Period: 4 weeks after the last dose 
Total duration of patient participation: The maximum duration of each patient’s participation in the 
study is expected to be approximately 152 weeks, inclusive of the Screening, Treatment and 
Observation, and Safety Follow-up Periods. The maximum study duration will ultimately depend upon 
patient enrollment from other completed studies of SRP-5051. 
NUMBER OF PATIENTS:  
The number of patients in this LTE study will be determined by the number of patients who participate 
in other studies administering SRP-5051.  
Up to 60 patients are planned to enroll in this LTE study upon completing a Phase 1 (ie, the completed 
Study 5051-101) or Phase 2 (eg, the ongoing Study 5051-201) study of SRP-5051
  
 
 
INCLUSION/EXCLUSION CRITERIA: 
Note: Patients who do not meet eligibility criteria (ie, screen failures) may be re-screened at the 
Investigator’s discretion. 
Inclusion Criteria 
A patient must meet all of the following criteria to be eligible to participate in this study: 
1. Has completed a study in which SRP-5051 was administered. 
2. Has not subsequently received treatment with any investigational therapy for DMD. 
3. If sexually active, agrees to use a male condom during such activity for the entire duration of the 
study and for 90 days after the last dose. The sexual partner must also use a medically 
acceptable form of contraceptive during this period.  
4. Is willing to provide informed consent or informed assent (if applicable) and has (a) parent(s) or 
legal guardian(s) who is (are) willing to provide informed consent for the patient to participate 
in the study. 
5. Is able to understand and comply with all the study requirements and, if under 18 years of age, 
had as (a) parent(s) or legal guardian(s) who is (are) able to understand and comply with all the 
study requirements. 
 
 
 
 
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NAME OF COMPANY 
Sarepta Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 USA 
Phone: +1-617-274-4000 
NAME OF FINISHED PRODUCT 
SRP-5051 Injection 
 
NAME OF ACTIVE INGREDIENT 
SRP-5051 
Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study: 
1. Initiation or change of dosing (except for modifications to accommodate changes in weight or 
changes in standard of care) since entering a study administering SRP-5051 for any of the 
following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking agents, 
β-blockers, and potassium. 
2. Requires anti-arrhythmic and/or diuretic therapy for heart failure.  
3. Use of any herbal medication/supplement containing aristolochic acid. 
4. Treatment with any experimental therapy since entering a study administering SRP-5051, or 
with any experimental gene therapy for the treatment of DMD at any time. 
5. Use of any aminoglycoside antibiotic or statin since entering a study administering SRP-5051. 
6. Initiation or change of dosing since completing a study administering SRP-5051 for  
over-the-counter preparations, such as herbal/nonherbal supplements, vitamins, minerals, and  
homeopathic preparations. 
7. Major surgery since entering a study administering SRP-5051, or planned surgery or procedures 
that would interfere with the conduct of this study. 
8. Presence of other clinically significant illness, including cardiac, pulmonary, hepatic, renal, 
hematologic, immunologic, or behavioral disease, or infection or malignancy. 
9. Any other condition that, in the Investigator’s opinion, could interfere with the patient’s 
participation in this trial. 
10. Any patient who, in the Investigator’s opinion, seems unable/unwilling to comply with the  
study procedures. 
11. Any patient who is taking medications that increase the risk of bleeding in the Investigator’s 
opinion (eg, anticoagulants, antiplatelet agents, novel oral anticoagulants, selective 
norepinephrine reuptake inhibitors, etc.) 
 
DOSE/ROUTE/REGIMEN (TEST ARTICLE): 
SRP-5051 drug product 
.  
The drug product is supplied for investigational use in single-use, 
 glass vials containing 
 of 
the active pharmaceutical ingredient. SRP-5051 drug product is intended 
 
 for intravenous 
(IV) administration.  
Each patient will receive SRP-5051 Q4W for a duration of approximately 144 weeks, at the highest dose 
determined by an SRC or IDMC to be safe and tolerable in other relevant studies of SRP-5051 and 
confirmed by the SRC for this LTE study, administered by IV infusion over a period of 
 
. 
REFERENCE TREATMENT: None 
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NAME OF COMPANY 
Sarepta Therapeutics, Inc. 
215 First Street 
Cambridge, MA 02142 USA 
Phone: +1-617-274-4000 
NAME OF FINISHED PRODUCT 
SRP-5051 Injection 
 
NAME OF ACTIVE INGREDIENT 
SRP-5051 
STATISTICAL METHODS: 
Sample Size 
The study sample size will be determined by the number of patients who participate in other studies 
administering SRP-5051. Patients are planned to roll over into this LTE study from multiple clinical 
trials, including trials that are yet to commence. 
Analysis Sets 
The following analysis sets will be used for the primary and secondary endpoints: 
• 
Safety Set: Defined as all patients who enroll in the study and have started the study drug 
(SRP-5051) infusion. The dose group will be designated according to the actual dose received. 
This analysis set will be used for safety analyses. 
• 
PK Set: Defined as all patients who enroll in the study, have started the study drug (SRP-5051) 
infusion, and have at least 1 PK concentration data collection. This analysis set will be used for 
PK analyses.  
The analysis sets to be used for other endpoints and/or additional analyses will be defined in the 
statistical analysis plan (SAP). 
Statistical Analysis Methods 
The following methods will be used for the primary and secondary endpoints: 
Safety Analyses 
Adverse events and other safety assessments will be summarized descriptively.  
PK Analyses 
Plasma concentrations at predose, Cmax (end of infusion), and approximately 4 to 6 hours postdose will 
be summarized descriptively. Plasma concentration data may be evaluated and combined with other 
clinical PK data from other studies administering SRP-5051.  
 
Interim Analysis 
No formal interim analysis is planned. 
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2. 
SCHEDULE OF EVENTS  
The study Schedule of Events is presented in Table 1.


 
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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND  
LIST OF FIGURES  
TABLE OF CONTENTS 
TITLE PAGE .......................................................................................................................... 1 
SIGNATURE PAGE FOR SPONSOR ..................................................................................... 2 
INVESTIGATOR’S AGREEMENT ........................................................................................ 3 
1. 
SYNOPSIS ........................................................................................................... 4 
2. 
SCHEDULE OF EVENTS .................................................................................. 10 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ............. 17 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .......................... 24 
5. 
INTRODUCTION ............................................................................................... 27 
5.1. 
Duchenne Muscular Dystrophy ............................................................................ 27 
5.2. 
Phosphorodiamidate Morpholino Oligomers and Peptide-Conjugated 
Phosphorodiamidate Morpholino Oligomers......................................................... 28 
5.2.1. 
Phosphorodiamidate Morpholino Oligomers......................................................... 28 
5.2.2. 
Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers .......................... 28 
5.2.2.1. 
SRP-5051............................................................................................................ 28 
5.3. 
Nonclinical Experience with SRP-5051 ................................................................ 29 
5.3.1. 
Nonclinical Summary .......................................................................................... 29 
5.4. 
Clinical Experience with SRP-5051 ..................................................................... 30 
5.4.1. 
Completed Studies of SRP-5051 .......................................................................... 30 
5.4.1.1. 
Study 5051-101 (Phase 1 Single-Ascending-Dose Study in DMD Patients) ........... 30 
5.4.2. 
Ongoing Studies of SRP-5051.............................................................................. 31 
5.4.2.1. 
Study 5051-103 (Phase 1 Single-Ascending-Dose Study in Healthy  
Male Subjects)..................................................................................................... 31 
5.4.2.2. 
Study 5051-201 (Phase 2, Two-Part, Multiple-Ascending-Dose Study in 
DMD Patients) .................................................................................................... 31 
5.5. 
Rationale for the Current Study ............................................................................ 32 
5.6. 
Benefit and Risk Assessment ............................................................................... 32 
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6. 
STUDY OBJECTIVES AND ENDPOINTS ......................................................... 34 
6.1. 
Objectives ........................................................................................................... 34 
6.1.1. 
Primary Objective................................................................................................ 34 
6.1.2. 
Secondary Objectives .......................................................................................... 34 
6.2. 
Endpoints ............................................................................................................ 34 
6.2.1. 
Primary Endpoint ................................................................................................ 34 
6.2.2. 
Secondary Endpoints ........................................................................................... 34 
7. 
INVESTIGATIONAL PLAN .............................................................................. 36 
7.1. 
Overall Study Design........................................................................................... 36 
7.2. 
Dose Selection Rationale ..................................................................................... 38 
7.3. 
Stopping Rules .................................................................................................... 39 
7.3.1. 
Stopping Rules for Liver Test Results .................................................................. 39 
7.3.2. 
Stopping Rules for Renal Test Results.................................................................. 40 
7.3.3. 
Stopping Rules for Hypersensitivity Adverse Events ............................................ 40 
7.3.4. 
Stopping Rules for Platelet Count Results............................................................. 40 
7.3.5. 
Stopping Rules Are Not Applicable for Rhabdomyolysis ...................................... 40 
7.4. 
Trial Discontinuation ........................................................................................... 40 
7.5. 
Study Committees ............................................................................................... 41 
7.5.1. 
Safety Review Committee.................................................................................... 41 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS .......................................... 42 
8.1. 
Number of Patients .............................................................................................. 42 
8.2. 
Patient Inclusion Criteria ..................................................................................... 42 
8.3. 
Patient Exclusion Criteria .................................................................................... 42 
8.4. 
Completion of a Patient’s Participation in the Study.............................................. 43 
8.5. 
Completion of the Trial........................................................................................ 43 
8.6. 
Patient Withdrawal Criteria.................................................................................. 43 
9. 
TREATMENT OF PATIENTS ............................................................................ 45 
9.1. 
Description of Study Drug ................................................................................... 45 
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9.1.1. 
Packaging and Labeling ....................................................................................... 46 
9.1.2. 
Storage................................................................................................................ 46 
9.2. 
Treatment Administered ...................................................................................... 46 
9.2.1. 
Dose Modification Criteria................................................................................... 47 
9.2.2. 
Dose Interruption Criteria .................................................................................... 47 
9.2.2.1. 
Dose Interruption/Delay Due to Laboratory Parameters Meeting  
Relevant Criteria ................................................................................................. 47 
9.3. 
Safety Monitoring................................................................................................ 48 
9.3.1. 
Safety Monitoring for Liver Chemistry Tests........................................................ 48 
9.3.1.1. 
Additional Investigations for Liver Function ........................................................ 48 
9.3.2. 
Safety Monitoring for Renal Function .................................................................. 49 
9.3.2.1. 
Additional Investigations for Renal Function ........................................................ 49 
9.3.3. 
Safety Monitoring for Hypersensitivity ................................................................ 52 
9.3.3.1. 
Additional Investigations for Hypersensitivity ...................................................... 52 
9.3.4. 
Safety Monitoring for Platelet Count Results ........................................................ 52 
9.3.4.1. 
Additional Investigations for Platelet Count.......................................................... 52 
9.3.5. 
Safety Monitoring for Rhabdomyolysis ................................................................ 53 
9.3.5.1. 
Additional Investigations for Rhabdomyolysis...................................................... 53 
9.4. 
Randomization and Blinding ................................................................................ 53 
9.5. 
Prior and Concomitant Medications ..................................................................... 53 
9.6. 
Treatment Compliance......................................................................................... 54 
10. 
STUDY ASSESSMENTS.................................................................................... 55 
10.1. 
Safety Assessments ............................................................................................. 55 
10.1.1. 
Adverse Events ................................................................................................... 55 
10.1.2. 
Vital Sign Measurement, Weight, and Height ....................................................... 55 
10.1.3. 
Physical Examination .......................................................................................... 55 
10.1.4. 
Clinical Laboratory Tests ..................................................................................... 56 
10.1.4.1. 
Unscheduled Laboratory Assessments .................................................................. 57 
10.1.5. 
Designation of Clinical Significance .................................................................... 57 
10.1.6. 
Electrocardiogram ............................................................................................... 57 
10.1.7. 
Concomitant Medications, Procedures, and Therapies........................................... 57 


 
 
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10.2. 
Pharmacokinetic Assessments .............................................................................. 57 
10.2.1. 
Blood Sample Collection ..................................................................................... 57 
11. 
ADVERSE EVENTS AND OTHER SAFETY INFORMATION.......................... 64 
11.1. 
Definitions .......................................................................................................... 64 
11.1.1. 
Adverse Event ..................................................................................................... 64 
11.1.2. 
Serious Adverse Event ......................................................................................... 64 
11.1.3. 
Adverse Events of Special Interest ....................................................................... 65 
11.1.3.1. 
AESI Criteria for Liver Test Results..................................................................... 65 
11.1.3.2. 
AESI Criteria for Renal Test Results .................................................................... 65 
11.1.3.3. 
AESI Criteria for Hypersensitivity ....................................................................... 65 
11.1.3.4. 
AESI Criteria for Platelet Count Results ............................................................... 65 
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11.1.3.5. 
AESI Criteria for Rhabdomyolysis ....................................................................... 65 
11.1.4. 
Overdose ............................................................................................................. 66 
11.1.5. 
Medication Error ................................................................................................. 66 
11.1.6. 
Accidental/Occupational Exposure....................................................................... 66 
11.2. 
Collection of Adverse Events ............................................................................... 66 
11.2.1. 
Clinical Laboratory Abnormalities ....................................................................... 67 
11.2.2. 
Reporting Disease Progression ............................................................................. 67 
11.3. 
Classification of Adverse Events .......................................................................... 67 
11.3.1. 
Relationship to Investigational Product ................................................................ 67 
11.3.2. 
Relationship to Study Procedures ......................................................................... 68 
11.3.3. 
Relationship to Underlying Disease...................................................................... 68 
11.3.4. 
Severity of Adverse Events .................................................................................. 68 
11.3.5. 
Outcome of Adverse Events................................................................................. 69 
11.3.6. 
Action Taken Regarding the Investigational Drug Product .................................... 69 
11.3.7. 
Expectedness of Adverse Events .......................................................................... 69 
11.4. 
Recording Adverse Events ................................................................................... 69 
11.4.1. 
Reporting Serious Adverse Events ....................................................................... 70 
11.4.1.1. 
Serious Adverse Events ....................................................................................... 70 
11.4.1.2. 
Suspected Unexpected Serious Adverse Reactions (SUSARs)............................... 70 
11.4.2. 
Reporting Special Situations ................................................................................ 70 
11.4.2.1. 
Pregnancy ........................................................................................................... 70 
11.4.2.2. 
Overdose ............................................................................................................. 70 
11.4.2.3. 
Medication Error ................................................................................................. 70 
11.4.2.4. 
Accidental/Occupational Exposure....................................................................... 71 
11.4.2.5. 
Adverse Events of Special Interest ....................................................................... 71 
11.4.3. 
Miscellaneous ..................................................................................................... 71 
11.4.3.1. 
Unblinding Due to a Medical Emergency ............................................................. 71 
11.4.3.2. 
Responsibilities of the Investigator....................................................................... 71 
11.4.3.3. 
Responsibilities of the Sponsor ............................................................................ 71 
12. 
DATA COLLECTION, QUALITY ASSURANCE, AND MANAGEMENT ........ 72 
12.1. 
Recording of Data ............................................................................................... 72 


 
 
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12.2. 
Quality Assurance ............................................................................................... 72 
12.3. 
Retention of Study Documents ............................................................................. 72 
13. 
STATISTICS ...................................................................................................... 74 
13.1. 
Analysis Endpoints .............................................................................................. 74 
13.2. 
Analysis Sets ....................................................................................................... 74 
13.3. 
Statistical Methods .............................................................................................. 74 
13.3.1. 
Safety Analyses ................................................................................................... 74 
13.3.1.1. 
Adverse Events ................................................................................................... 74 
13.3.1.2. 
Other Safety Assessments .................................................................................... 75 
13.3.1.3. 
Prior and Concomitant Medications ..................................................................... 75 
13.3.2. 
Pharmacokinetic Analyses ................................................................................... 76 
13.3.3. 
Summaries of Demographics, Baseline Characteristics, and Other Analyses .......... 76 
13.3.3.1. 
Patient Disposition, Demographics, and Baseline Characteristics .......................... 76 
13.4. 
Interim Analysis .................................................................................................. 76 
13.5. 
Sample Size ........................................................................................................ 76 
14. 
ETHICS AND OTHER SPECIAL REQUIREMENTS ......................................... 77 
14.1. 
Compliance with Ethical and Regulatory Guidelines............................................. 77 
14.2. 
Institutional and Ethics Review ............................................................................ 77 
14.3. 
Informed Consent ................................................................................................ 77 
14.4. 
Compliance with the Protocol .............................................................................. 77 
14.5. 
Confidentiality .................................................................................................... 78 
15. 
STUDY DOCUMENTATION AND GENERAL INFORMATION ...................... 79 
15.1. 
Essential Study Documents .................................................................................. 79 
15.2. 
General Information ............................................................................................ 79 
15.3. 
Dissemination of Study Results............................................................................ 79 
15.4. 
Publication Policy................................................................................................ 79 
15.5. 
Product Handling and Complaints Reporting ........................................................ 80 
16. 
LIST OF REFERENCES ..................................................................................... 81 
 


 
 
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LIST OF TABLES 
Table 1: 
Study Schedule of Events .................................................................................... 11 
Table 2: 
Study Drug Specifications.................................................................................... 45 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic ...................................................................................... 38 
 
  
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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation  
Definition 
 
 
 
 
ACE 
Angiotensin-converting enzyme 
ADL 
Activities of daily living 
ADME 
Absorption, distribution, metabolism, excretion 
AE 
Adverse event 
AESI 
Adverse event of special interest 
aHUS 
Atypical hemolytic uremic syndrome  
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ARB 
Angiotensin receptor-blocking 
AST 
Aspartate aminotransferase 
AUC0-last 
Area under the concentration-time curve from time 0 to time of the last 
quantifiable concentration 
 
 
BW 
Body weight 
CK 
Creatine kinase 
Cmax 
Maximum observed plasma concentration 
CPP 
Cell-penetrating peptide  
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMD 
Duchenne muscular dystrophy 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EOS 
End of Study 
 
 
FVC 
Forced vital capacity 
GCP 
Good Clinical Practice 
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Abbreviation  
Definition 
GFR 
Glomerular filtration rate 
GGT 
Gamma glutamyl transferase 
GLDH 
Glutamate dehydrogenase 
GLP 
Good Laboratory Practice 
HPF 
High-power field 
ICH 
International Council on Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IP 
Investigational product 
IRB 
Institutional Review Board 
IRR 
Infusion-related reaction 
IV 
Intravenous(ly) 
IVAD 
Implanted venous access device 
LTE 
Long-term extension 
MedDRA 
Medical Dictionary for Regulatory Activities 
 
 
 
 
MRI 
Magnetic resonance imaging 
mRNA 
Messenger ribonucleic acid 
MTD 
Maximum tolerated dose 
NHP 
Nonhuman primate 
NOAEL 
No-observed-adverse-effect level 
 
 
OECD 
Organisation for Economic Co-operation and Development 
 
 
PD 
Pharmacodynamic(s) 
PK 
Pharmacokinetic(s) 
 
 
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Abbreviation  
Definition 
PMO 
Phosphorodiamidate morpholino oligomer 
PPMO 
Peptide-conjugated phosphorodiamidate morpholino oligomer  
PT 
Preferred term 
 
 
Q2W 
Once every 2 weeks 
Q4W 
Once every 4 weeks 
 
 
QUA 
Quantitative urinalysis 
QW 
Once weekly 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
SUSAR 
Suspected unexpected serious adverse reaction 
SWFI 
Sterile water for injection 
t1/2 
Half-life 
TEAE 
Treatment-emergent adverse event 
UACR 
Urinary albumin to creatinine ratio 
ULN 
Upper limit of normal 
UPCR 
Urinary protein to creatinine ratio 
WHODrug 
World Health Organization Drug Dictionary 
WNL 
Within normal limits 
Note: Abbreviations that only appear in a table or figure are defined within the footer of the corresponding table  
or figure. 
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5. 
INTRODUCTION 
5.1. 
Duchenne Muscular Dystrophy 
Duchenne muscular dystrophy (DMD) is a rare, serious, life-threatening, X-linked recessive, 
degenerative neuromuscular disease caused by mutations in the dystrophin gene, with a 
worldwide incidence of 1 in 3500 to 5000 newborn boys, irrespective of geographical region, 
race, or population density (Centers for Disease Control and Prevention 2009, Emery 1991). The 
mutations that cause DMD typically disrupt the dystrophin messenger ribonucleic acid (mRNA) 
reading frame and prevent production of the corresponding protein. Dystrophin is a critically 
important part of a protein complex that connects the cytoskeleton of a muscle fiber to the cell 
membrane and extracellular matrix and acts to prevent muscle membrane damage during 
eccentric contraction. In the absence of dystrophin, the stress of muscle contraction causes 
widespread, chronic, and progressive muscle damage and degeneration, with replacement by  
fat and fibrotic tissue. The clinical effect of this disrupted dystrophin reading frame is  
ultimately fatal.  
The progression of DMD follows a highly predictable disease course. Significant motor deficits 
may be present during the first year of life, but a diagnosis is usually made between the ages of 
3 to 5 years, when children begin to show functional symptoms (eg, waddling gait, toe walking, 
and difficulty climbing stairs). Over time, ambulation becomes increasingly abnormal, and by  
8 years of age, most patients have lost the ability to rise from the floor and climb stairs, have an 
increasingly labored gait, and often fall while walking. By 10 to 14 years of age, most patients 
are wheelchair-dependent. Weakness of the arms and increasingly limited upper-limb function, 
contractures, decubitus ulcers, and scoliosis (which often requires surgery) occur frequently 
(Brooke 1989). While pulmonary and cardiac function are generally normal during early 
childhood, the cardiac and diaphragmatic muscles of DMD patients progressively weaken during 
late childhood and adolescence, leading to eventual dependence on ventilatory support  
(Brooke 1989, Eagle 2002).  
In addition to clinical manifestations, patients with DMD have greatly elevated creatine kinase 
(CK) values due to leakage of the enzyme from degenerating muscle fibers (Zatz 1991). Early in 
the disease, CK levels are usually 50 × to 300 × the upper limit of normal (ULN) (normal range:  
37 U/L to 430 U/L), and levels tend to decrease over time as muscle is lost and replaced by 
fibrotic tissue and fat. High transaminase levels (alanine aminotransferase [ALT] and aspartate 
aminotransferase [AST] up to approximately 22 × ULN) and lactate dehydrogenase levels, 
originating from degenerating muscle, are also generally observed in DMD patients 
(McMillan 2011). Creatinine levels tend to be low or low to normal due to decreased muscle 
mass (Viollet 2009). 
Existing interventions are largely supportive in nature and include bracing, muscle-stretching 
exercises to avoid onset of contractures, tendon-release surgery, and eventual wheelchair use and 
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Current pharmacologic treatments, such as corticosteroids, focus on alleviation of symptoms, but 
do not address the underlying cause of the disease. Corticosteroids may prolong ambulation, 
delay the onset of scoliosis, and improve performance on some measures of clinical function 
(Beenakker 2005, Pradhan 2006).  
However, their benefits are only temporary, and their use is often limited by numerous side 
effects, including growth inhibition, effects on pubertal changes, weight gain, behavioral 
changes, osteoporosis, Cushingoid facies and habitus, and cataracts (Biggar 2006, Manzur 2008). 
5.2. 
Phosphorodiamidate Morpholino Oligomers and 
Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers  
5.2.1. 
Phosphorodiamidate Morpholino Oligomers 
Antisense ribonucleic acid (RNA) therapeutics are a class of compounds composed of 
heterocyclic nucleobases (adenine, cytosine, guanine, and thymine, or analogues) linked together 
on an oligomer backbone that are designed to hybridize with specific complementary RNA 
targets via Watson-Crick base pairing. Ribonucleic acid therapeutics can be synthesized to bind 
targeted RNA sequences in a pathogen or pathogenic process to treat a wide range of diseases 
through positively or negatively modulating gene expression. Additionally, RNA therapeutics 
can be synthesized to target a pre-mRNA in the nucleus of a cell to influence the splicing process 
that creates a mature mRNA. Referred to as “exon skipping”, this approach allows determination 
of which exons will be incorporated into the mature mRNA to be translated into the  
protein product.  
Phosphorodiamidate morpholino oligomers (PMOs) are a class of synthetic molecules based on a 
redesign of the natural nucleic acid structure. The PMOs are distinguished from natural nucleic 
acids and other oligonucleotide therapeutic platforms by the attachment of nucleobases to a 
6-membered morpholine ring, as opposed to the 5-membered ribose ring found in RNA and 
deoxyribonucleic acid. Moreover, the morpholine rings are linked through uncharged 
phosphorodiamidate moieties, as opposed to negatively charged phosphodiester linkages found 
in natural nucleic acids. These structural differences were designed to increase systemic stability 
and address safety issues seen with some earlier oligonucleotide modified backbone chemistries. 
5.2.2. 
Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers 
5.2.2.1. 
SRP-5051 
The peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) SRP-5051 is 
composed of 2 covalently bonded moieties, corresponding to the classical pharmacology concept 
of “message and address.”  
The first moiety is a PMO designed to hybridize to an internal nucleobase sequence of exon 51 
in the dystrophin gene pre-mRNA to induce the skipping of exon 51 in the mature mRNA, 
thereby restoring the disrupted open reading frame caused by deletion mutations of the 
dystrophin gene, which in turn leads to the production of an internally shortened dystrophin 
protein. The second moiety is a cell-penetrating peptide (CPP) that greatly enhances intracellular 
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5.3. 
Nonclinical Experience with SRP-5051 
Nonclinical studies of SRP-5051 conducted to date are summarized below. Refer to the  
SRP-5051 Investigator’s Brochure for additional details of each study. 
5.3.1. 
Nonclinical Summary 
Clinical development of SRP-5051 is supported by nonclinical evaluation of in vitro absorption, 
distribution, metabolism, and excretion (ADME) studies, nonclinical safety pharmacology 
studies, and nonclinical toxicity/toxicokinetic studies of SRP-5051 conducted in  animal 
species: the mouse, nonhuman primate (NHP)
. 
All safety pharmacology and toxicity studies of SRP-5051 considered necessary for human 
safety assessment were conducted in accordance with the Organization for Economic  
Co-operation and Development (OECD) Test Guidelines and Principles of Good Laboratory 
Practice (GLP) in countries (United States, Canada) that are members of the OECD Mutual 
Acceptance of Data program.  
 
 
 
 
 
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5.4. 
Clinical Experience with SRP-5051 
Clinical experience with SRP-5051 to date is summarized below. Refer to the SRP-5051 
Investigator’s Brochure for additional details of each clinical study. 
5.4.1. 
Completed Studies of SRP-5051 
One study of SRP-5051 (Study 5051-101) has been completed to date, as summarized below in  
Section 5.4.1.1.  
5.4.1.1. 
Study 5051-101 (Phase 1 Single-Ascending-Dose Study in DMD Patients) 
The completed Study 5051-101 was a Phase 1, first-in-human, open-label trial to evaluate the 
safety, tolerability, and PK of a single dose of SRP-5051—
  
—in patients with DMD amenable to exon 51-skipping treatment.  
 
 
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A total of 
 patients were enrolled and dosed in Study 5051-101 
 
 
 
 
 
.  
5.4.2. Ongoing Studies of SRP-5051 
In addition to this long-term extension (LTE) study, 2 other studies of SRP-5051 remain ongoing 
to date, as summarized below in Sections 5.4.2.1 and 5.4.2.2.  
5.4.2.1. 
Study 5051-103 (Phase 1 Single-Ascending-Dose Study in Healthy  
Male Subjects)  
Study 5051-103 is an open-label, single-center study conducted in healthy male subjects. The 
primary objective of the study is to evaluate the safety and tolerability 
 
 of SRP-5051 
 
 administered as an IV infusion in healthy subjects. The secondary objective is to determine 
the PK of the  doses in this population.  
5.4.2.2. 
Study 5051-201 (Phase 2, Two-Part, Multiple-Ascending-Dose Study in  
DMD Patients) 
Study 5051-201 is a multicenter, open-label study conducted in DMD patients amenable to  
exon 51 skipping. The study comprises 2 parts: Part A, which is primarily intended to evaluate 
the safety and tolerability of SRP-5051 at multiple ascending dose levels (4 mg/kg [n = 3],  
10 mg/kg [n = 3], 20 mg/kg [n = 3], 30 mg/kg [n = 6], and 40 mg/kg [n = 6]) and determine the 
MTD, and Part B, which is primarily intended to evaluate dystrophin protein levels after 
treatment with SRP-5051 at the MTD and which includes an expansion cohort (n = ~15). 
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5.5. 
Rationale for the Current Study 
This LTE study is intended for DMD patients who have completed other studies administering  
SRP-5051. The trial is being conducted to offer participants who have received SRP-5051 in 
other trials the opportunity to continue dosing with SRP-5051. The trial is also intended to gain 
additional insight into the safety and efficacy of treatment with SRP-5051 and the potential 
possibility for patients to experience clinical benefit.  
Current data from completed chronic toxicology studies in mice and NHPs 
 
 offer a reasonable assurance of minimal risk for Q4W administration  
of SRP-5051.  
Data from other clinical studies of SRP-5051, 
 are 
anticipated to further inform the continued conduct of this study. 
5.6. 
Benefit and Risk Assessment  
The clinical benefit of SRP-5051 for the treatment of DMD patients is currently under 
evaluation, but is not yet known. However, in nonclinical studies, PD proof of concept for the 
dose-dependent exon 51-skipping activity of SRP-5051 has been demonstrated in various 
preparations of skeletal muscle obtained from DMD patients in vitro; in transgenic mice 
harboring the complete human DMD gene; and in skeletal and cardiac muscle following  
single-dose, 
 IV 
administration of SRP-5051 in studies conducted in healthy NHPs in vivo. Pharmacokinetic/PD 
analyses support an anticipated pharmacodynamically relevant response at selected doses of 
SRP-5051, administered Q4W, in both healthy human subjects and DMD patients.  
Additional supportive data for the PD mechanism of action and enhanced delivery of SRP-5051 
are provided by studies of a murine surrogate PMO, AVI-4225, which causes exon 23 skipping 
in pre-mRNA in a murine DMD model (mdx mouse) in vivo (refer to the current SRP-5051 
Investigator’s Brochure for details). The observed levels of exon skipping and dystrophin protein 
(as assessed in a quantitative Western blot assay) with the CPP-conjugated AVI-4225 were 
superior to those observed with unconjugated AVI-4225 at equivalent doses. Specifically, 
dystrophin levels were > 10-fold higher after CPP-conjugated AVI-4225 treatment compared to 
unconjugated AVI-4225 treatment. In the mdx mouse, exon-skipping levels were observed to 
persist for up to 3 months after a single dose of CPP-conjugated AVI-4225.  
These results provide strong evidence to support both the proposed mechanism of action of exon 
skipping and the desired pharmacological effect on dystrophin protein content. Therefore, it is 
possible that treatment with SRP-5051 may confer benefit via production of dystrophin, which 
may ultimately lead to positive clinical effects on muscle function in DMD patients amenable to 
exon 51 skipping.  
In nonclinical safety studies of SRP-5051, no evidence of central nervous system effects, 
genotoxicity, male reproductive toxicity, or immune responses was detected.  
 
 
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Cardiovascular findings were limited  
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
  
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
As of 29 November 2019, the SRP-5051 clinical development program consisted of 4 clinical 
trials, including 2 Phase 1 studies (the completed Study 5051-101 and ongoing Study 5051-103); 
this Phase 1/2 LTE study; and 1 Phase 2 study (the ongoing Study 5051-201).  
As reported in the SRP-5051 Investigator’s Brochure,  SAEs—  reported as of the  
29 November 2019 data cutoff date, and  reported subsequent to that data cutoff—were 
reported in a total of  clinical study participants receiving SRP-5051. All of these SAEs were 
assessed as not related to SRP-5051 by both the Sponsor and the reporting Investigators. No new 
safety trends were detected in the distribution of the SAEs, cumulatively. There were no fatal 
cases reported from the clinical development program. 
Overall, these safety data suggest that that SRP-5051 has an acceptable safety profile in DMD 
patients. Information about important risks, potential risks, and other risks associated with  
SRP-5051 treatment, as well as details of the AEs reported in clinical study participants 
receiving SRP-5051, are provided in the SRP-5051 Investigator’s Brochure. 
 
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6. 
STUDY OBJECTIVES AND ENDPOINTS 
6.1. 
Objectives 
6.1.1. 
Primary Objective 
• To evaluate the AE profile of repeat Q4W administration of SRP-5051 
6.1.2. 
Secondary Objectives 
• To determine the PK of SRP-5051 following repeat Q4W administration 
• To evaluate additional safety and tolerability of repeat Q4W administration  
of SRP-5051  
6.2. 
Endpoints 
6.2.1. 
Primary Endpoint 
• Incidence of AEs 
6.2.2. 
Secondary Endpoints 
• Plasma concentrations determined at predose, the maximum observed drug 
concentration (Cmax), and 4 to 6 hours after the end of the infusion 
• Frequency of clinically relevant abnormalities, as assessed by vital sign 
measurements, physical examination findings, clinical laboratory tests, and ECGs 
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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is a Phase 1/2, multicenter, open-label, LTE study for patients who have completed other 
studies administering SRP-5051. The study will assess the safety, tolerability, and PK of  
SRP-5051 administered Q4W for a duration of approximately 144 weeks in patients with DMD 
who have deletion mutations amenable to exon 51-skipping treatment.  
Up to 60 patients are planned to enroll in this LTE study upon completing a Phase 1 (ie, the 
completed Study 5051-101 [Section 5.4.2.1]) or Phase 2 (eg, the ongoing Study 5051-201 
[Section 5.4.2.2]) study of SRP-5051
 
 
.  
Each patient will complete 3 study periods: Screening, Treatment and Observation, and  
Safety Follow-up. Details are as follows: 
Screening Period 
Patients who have completed other studies administering SRP-5051 are eligible to participate in 
this LTE study. For patients who elect to participate in this trial, informed consent is to be 
obtained at or immediately following the End of Study (EOS) visit in the original study 
administering SRP-5051. Patients who do not provide consent at the original study EOS visit 
will have 
 the time of that visit to elect to participate in and provide 
informed consent for this trial. Every effort will be made to ensure that the patient will not 
experience any interruption in dosing of SRP-5051 during the transition from the original study 
to this LTE study. 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen-failure information is required to 
ensure transparent reporting of screen-failure participants to meet publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demographics, 
screen-failure details, eligibility criteria, and any SAE information. 
Individuals who do not meet the criteria for participation in this study (ie, screen failures) may be 
re-screened at the Investigator’s discretion. 
Treatment and Observation Period 
Patients who enroll in this study will receive their first Q4W dose of SRP-5051 on Day 1 of the 
Treatment and Observation Period. While it is expected that patients will receive their Q4W 
infusions of SRP-5051 at a designated study site (ie, study clinic), home infusions may be an 
option for dosing visits if circumstances impact a patient’s ability to travel by any applicable 
means (including air travel, personal vehicle travel, travel via car service, wheelchair van travel, 
etc.). Prior approval from the Sponsor Medical Monitor is required for any home infusion visit.  
 
 
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Initially, patients will be administered the highest dose determined by a Safety Review 
Committee (SRC) or Independent Data Monitoring Committee (IDMC) to be safe and tolerable, 
as justified in other relevant studies of SRP-5051 in accordance with the procedure defined in the 
relevant study protocol or Charter, with the final dose confirmation to be made by the SRC for 
this LTE study. 
The SRC for this LTE study (Section 7.5.1) may make the recommendation to proceed to a 
higher dose level as per the guidance provided in the SRC Charter.  
Upon determination of higher dose(s) deemed safe and tolerable in other relevant studies of  
SRP-5051—and only upon receipt of a formal letter from the Sponsor—dose escalation for all 
patients enrolled in this LTE study may proceed to the highest dose determined by the 5051-102 
SRC to be safe and tolerable, starting at each patient’s next scheduled dosing visit (Table 1). 
Data and recommendations from other studies of SRP-5051 will be provided to the 5051-102 
SRC to inform the dose-escalation decision. 
Patients will continue SRP-5051 dosing Q4W. Vital sign measurements; physical examination 
findings; clinical laboratory tests; renal biomarkers; electrocardiograms (ECGs); 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
changes in concomitant 
medications and/or procedures; and AEs will all be assessed during scheduled visits (Table 1).  
Vital signs will be collected from the contralateral arm from which the blood samples are 
collected. Clinical laboratory tests will also be collected, approximately 
 after initial 
dosing and after each subsequent dose, for safety monitoring purposes. Refer to Section 9.3 for 
safety monitoring guidance. These laboratory assessments may be collected at the patient’s home 
or another convenient location, but must be analyzed centrally.  
Safety Follow-up Period 
Patients will be contacted by the clinic staff 
 after their last dose of SRP-5051 to assess 
AEs and changes in concomitant medications and/or procedures. Clinical laboratory tests will  
be collected at this time at the study site or another convenient location, and analyzed centrally.  
 after completing the Treatment and Observation Period, patients will be asked to 
complete the EOS visit. 
 vital sign 
measurements, physical examination findings, clinical laboratory tests, renal biomarkers, ECGs, 
changes in concomitant medications and/or procedures, and AEs will be assessed at the  
EOS visit.  
Patients who have received at least 1 dose of study drug and are withdrawn from treatment will 
be asked to complete an Early Termination visit (to complete the EOS assessments) 
approximately 
 after their last dose of SRP-5051, or within 
 of a 
withdrawal decision if early termination occurs after a missed dose.  
 
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7.3. 
 Stopping Rules 
Stopping rules for this study are detailed below in Sections 7.3.1 through 7.3.5. 
7.3.1. 
Stopping Rules for Liver Test Results 
In the event of laboratory results meeting the following criteria, and the event is without an 
alternative explanation as discussed with the Sponsor Medical Monitor, dosing of a patient 
with SRP-5051 will be stopped permanently; values that are not confirmed due to failure to retest 
or missing laboratory values will be presumed confirmed:  
• Gamma glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH) 
 × ULN, 
which is confirmed 
• GGT or GLDH 
 × ULN, which is confirmed and persists for 
 
• GGT or GLDH 
 × ULN, which is confirmed, and total bilirubin 
 × ULN or  
international normalized ratio (INR) 
 
• GGT or GLDH 
 × ULN, which is confirmed, and new appearance (ie, onset coincides 
with the changes in hepatic enzymes) of fatigue, nausea, vomiting, right upper-quadrant 
pain or tenderness, fever, rash, or eosinophilia 
 considered by the Investigator to 
be potentially related to hepatic inflammation 
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7.3.2. 
Stopping Rules for Renal Test Results 
 
 
 
7.3.3. 
Stopping Rules for Hypersensitivity Adverse Events 
In the event of a confirmed hypersensitivity AE meeting the following criteria, and the event is 
without an alternative explanation as discussed with the Sponsor Medical Monitor, dosing 
of a patient with SRP-5051 will be stopped permanently: 
• Anaphylaxis, anaphylactoid reaction, or angioedema  
• Any serious allergic reaction  
• Any serious, acute complement-mediated reaction (eg, atypical hemolytic uremic 
syndrome [aHUS], acute kidney injury, arteritis, myocarditis, pneumonitis, etc.)  
7.3.4. 
Stopping Rules for Platelet Count Results 
In the event of laboratory results meeting the following criteria, and the event is without an 
alternative explanation as discussed with the Sponsor Medical Monitor, dosing of a patient 
with SRP-5051 will be stopped permanently:  
• Platelet count 
 
7.3.5. 
Stopping Rules Are Not Applicable for Rhabdomyolysis 
Stopping rules are not applicable for rhabdomyolysis. In the event of a rhabdomyolysis AE, 
safety monitoring is to be implemented as instructed in Section 9.3.5. Dose interruption/delay 
may occur, as described in Section 9.2.2.1. 
7.4. 
Trial Discontinuation 
If the Sponsor, the Investigator, the Medical Monitor, the study monitor, Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC), or appropriate regulatory officials discover 
conditions arising during the study that indicate the study should be halted, or that a study center 
should be terminated, appropriate action may be taken after consultation among (at a minimum) 
the Sponsor, the Investigator, the IRB/IEC, and the Medical Monitor. 
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Conditions that may warrant termination of the study or an individual site include, but are not 
limited to, the following: 
• The discovery of an unexpected, serious, or unacceptable risk to patients enrolled in 
the study 
• A decision by the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product 
• Failure of the Investigator to enroll patients into the study at an acceptable rate 
• Failure of the Investigator to comply with pertinent regulations of IRB/IEC or 
appropriate regulatory authorities 
• Failure of the Investigator to comply with the protocol 
• Submission of knowingly false information from the research facility to the Sponsor, 
the study monitor, IRB/IEC, or regulatory authority 
• Insufficient adherence to protocol requirements consistent with the European Clinical 
Trial Directive 2005/28/EC 
7.5. 
Study Committees 
7.5.1. 
Safety Review Committee 
The SRC for this study will evaluate the study safety and tolerability data on an ongoing basis in 
order to ensure that the patients are not exposed to unreasonable or unnecessary risks.  
The SRC may also make the recommendation to proceed to a higher dose level as per the 
guidance provided in the SRC Charter. Upon determination of higher dose(s) deemed safe and 
tolerable in other relevant studies of SRP-5051—and only upon receipt of a formal letter from 
the Sponsor—dose escalation for all patients enrolled in this LTE study may proceed to the 
highest dose determined by the 5051-102 SRC to be safe and tolerable, starting at each patient’s 
next scheduled dosing visit (Table 1). Data and recommendations from other studies of  
SRP-5051 will be provided to the 5051-102 SRC to inform the dose-escalation decision. 
The activities and composition of the SRC are further detailed in the SRC Charter, which was 
ratified during the initial SRC meeting prior to the commencement of dosing of patients. The 
SRC Charter contains guidance for evaluation of available safety data and additional safety 
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8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1. 
Number of Patients 
The number of patients in this study will be determined by the number of patients who 
participate in other studies administering SRP-5051. 
Up to 60 patients with DMD who have completed a Phase 1 (ie, the completed Study 5051-101 
[Section 5.4.1.1]) or Phase 2 study (eg, the ongoing Study 5051-201 [Section 5.4.2.2]) of  
SRP-5051 
 
 
. 
8.2. 
Patient Inclusion Criteria 
Note: Patients who do not meet eligibility criteria may be re-screened at the  
Investigator’s discretion. 
A patient must meet all of the following criteria to be eligible to participate in this study: 
I 1. 
Has completed a study in which SRP-5051 was administered. 
I 2. 
Has not subsequently received treatment with any investigational therapy for DMD. 
I 3. 
If sexually active, agrees to use a male condom during such activity for the entire 
duration of the study and for 90 days after the last dose. The sexual partner must also 
use a medically acceptable form of contraceptive during this time frame.  
I 4. 
Is willing to provide informed consent or informed assent (if applicable) and has (a) 
parent(s) or legal guardian(s) who is (are) willing to provide informed consent for the 
patient to participate in the study. 
I 5. 
Is able to understand and comply with all the study requirements and, if under 18 
years of age, had as (a) parent(s) or legal guardian(s) who is (are) able to understand 
and comply with all the study requirements. 
8.3. 
Patient Exclusion Criteria 
A patient who meets any of the following criteria will be excluded from this study: 
E 1. 
Initiation or change of dosing (except for modifications to accommodate changes in 
weight or changes in standard of care) since entering a study administering SRP-5051 
for any of the following: angiotensin-converting enzyme (ACE) inhibitors, 
angiotensin receptor-blocking (ARB) agents, β-blockers, and potassium. 
E 2. 
Requires anti-arrhythmic and/or diuretic therapy for heart failure.  
E 3. 
Use of any herbal medication/supplement containing aristolochic acid. 
E 4. 
Treatment with any experimental therapy since entering a study administering  
SRP-5051, or with any experimental gene therapy for the treatment of DMD at  
any time. 
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E 5. 
Use of any aminoglycoside antibiotic or statin since entering a study administering  
  
SRP-5051. 
E 6. 
Initiation or change of dosing since completing a study administering SRP-5051 for 
over-the-counter preparations, such as herbal/nonherbal supplements, vitamins, 
minerals, and homeopathic preparations. 
E 7. 
Major surgery since entering a study administering SRP-5051, or planned surgery or 
procedures that would interfere with the conduct of this study. 
E 8. 
Presence of other clinically significant illness, including cardiac, pulmonary, hepatic, 
renal, hematologic, immunologic, or behavioral disease, or infection or malignancy. 
E 9. 
Any other condition that, in the Investigator’s opinion, could interfere with the 
patient’s participation in this trial. 
E 10. Any patient who, in the Investigator’s opinion, seems unable/unwilling to comply 
with the study procedures. 
E 11. Any patient who is taking medications that increase the risk of bleeding in the 
Investigator’s opinion (eg, anticoagulants, antiplatelet agents, novel oral 
anticoagulants, selective norepinephrine reuptake inhibitors, etc.) 
 
8.4. 
Completion of a Patient’s Participation in the Study 
A patient will be considered to have completed the study upon completion of the Safety  
Follow-up assessments as specified in the Schedule of Events (Table 1). 
8.5. 
Completion of the Trial 
The trial will be considered completed when all patients have completed the Safety Follow-up 
assessments as specified in the Schedule of Events (Table 1). The study duration will be 
contingent on enrollment. 
8.6. 
Patient Withdrawal Criteria 
Any patient can decide to withdraw from study participation at any time for any reason. In 
addition, the study Sponsor may decide to stop the study participation of any patient as deemed 
necessary. The Investigator may also stop the study participation of any patient at any time. 
Reasons for withdrawal from the study include, but are not limited to: 
• The patient was erroneously included in the study (ie, was found to not have met the 
eligibility criteria) 
• The patient experiences an intolerable or unacceptable AE 
• The patient is unable to comply with the requirements of the protocol 
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• Laboratory results during monitoring meet protocol-defined criteria for dosing 
discontinuation (refer to Section 9.3 for guidance on safety monitoring and dosing 
decisions and to Section 7.3 for the study stopping rules) 
The Investigator or study staff will document the reason(s) for treatment discontinuation.  
Patients who have received at least 1 dose of study drug and are withdrawn from treatment will 
be asked to complete an Early Termination visit (to complete the EOS assessments) 
approximately 
 after their last dose of SRP-5051, or within 
 of a 
withdrawal decision if early termination occurs after a missed dose. Any AEs are to be recorded 
through the EOS/Early Termination visit. 
 
  
Patients withdrawn from treatment will not be replaced. 
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9. 
TREATMENT OF PATIENTS 
9.1. 
Description of Study Drug 
SRP-5051 drug product is a 
. SRP-5051 drug product 
is supplied for investigational use in 
 of the active 
pharmaceutical ingredient.  
The SRP-5051 drug product is intended for reconstitution with 
 of sterile water for 
injection (SWFI), followed by dilution with 
 for IV 
administration. The diluents for reconstitution or preparation of the dosing solution are not 
supplied with the drug product. The SRP-5051 drug product will be supplied 
 
 
Details of the study drug are summarized in Table 2. Refer to the study-specific Pharmacy 
Manual for further information on packaging, labeling, and preparation instructions. 
Table 2: 
Study Drug Specifications 
Study drug name: 
SRP-5051 injection 
Strength: 
/vial 
Dosage formulation: 
 
NOTE: The drug product must initially be reconstituted 
with 
 of sterile water for injection and additionally 
diluted to the appropriate dose and volume in 
 
 prior to administration. 
Dosage: 
Initial dose will be the highest dose determined by a Safety 
Review Committee (SRC) or Independent Data Monitoring 
Committee to be safe and tolerable, as justified in other relevant 
studies of SRP-5051, with the final dose confirmation to be 
made by the SRC for this long-term extension study.  
Route of administration:  
Intravenous infusion, after reconstitution and dilution 
Dosing instructions: 
Infused over 
 
Packaging and labeling: 
 
SRP-5051 is supplied in single-use vials containing 
  
of SRP-5051. 
Each vial is labeled in accordance with applicable laws  
and regulations. 
 
 
 
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9.1.1. 
Packaging and Labeling 
Refer to the study-specific Pharmacy Manual for information on packaging, labeling, and dosage 
preparation instructions.  
The label text for the study drug product will include the following information: product 
name/identifier, cautionary statement, lot number (or alternative code), storage conditions, and 
the name of the study Sponsor. Additional information may be included in accordance with 
applicable local, national, or regional requirements. 
9.1.2. 
Storage 
The study drug product must be stored 
 
. Vials of investigational product (IP) must be stored in a secured, limited access area 
with appropriate temperature recording, controls, and monitoring. Details for storage can be 
found in the study-specific Pharmacy Manual. 
9.2. 
Treatment Administered 
Eligible patients will receive an IV infusion of SRP-5051 Q4W for approximately 144 weeks. While it is 
expected that patients will receive their Q4W infusions of SRP-5051 at a designated study site 
(ie, study clinic), home infusions may be an option for dosing visits if circumstances impact a 
patient’s ability to travel by any means. Prior approval from the Sponsor Medical Monitor is 
required for any home infusion visit.  
SRP-5051 is to be prepared for dosing by following the steps detailed in the study-specific 
Pharmacy Manual. 
Each patient will receive SRP-5051 by IV infusion over a period of 
. 
The Q4W dose of SRP-5051 will not exceed the highest dose determined by an SRC or IDMC to 
be safe and tolerable in other relevant studies of SRP-5051, with the final dose confirmation to 
be made by the SRC for this LTE study. 
SRP-5051 is to be administered through a peripheral IV. If peripheral access cannot be obtained, 
alternative methods of obtaining IV access must be attempted. An implanted venous access 
device (IVAD) is only to be considered, at the discretion of the Investigator, if alternative 
options have been attempted and access continues to be unsuccessful.  
If SRP-5051 is administered into an existing IV line, the line is to be flushed with normal saline 
before and after administration of SRP-5051. After SRP-5051 administration and the saline 
flush, the IVAD may be flushed with heparin in order to hep-lock the device prior to removal of 
the infusion line. 
No other medications may be administered concomitantly during the study drug infusion.  
All patients will be observed for at least 
 following the end of the infusion of study drug. 
In the absence of either a) infusion-related reactions (IRRs) (whether local or systemic) or b) 
other symptoms or signs of hypersensitivity associated with drug administration following  
 consecutive SRP-5051 administrations at the same dose level, monitoring beyond 
 
post-end of infusion is not required. 
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9.2.1. 
Dose Modification Criteria 
Patient-level dose modification guidance for this LTE study is provided below.  
Refer to Section 7.2.1 (dose escalation) and Section 7.3 (stopping rules) for study-level  
dose-modification information. 
9.2.2. 
Dose Interruption Criteria 
If a patient in this study experiences an AE that requires interruption of administration of study 
drug for 
 consecutive doses, the Investigator is to consult with the Medical Monitor to 
determine whether the patient may resume treatment. 
9.2.2.1. 
Dose Interruption/Delay Due to Laboratory Parameters Meeting  
Relevant Criteria 
If a patient has a scheduled dosing visit, but SRP-5051 administration is held due to laboratory 
parameters meeting relevant criteria (Section 9.3)—including any of the AEs of special interest 
(AESIs) defined in Section 11.1.3— the following study procedures are to be performed as 
scheduled (Table 1):  
• Safety laboratory assessments 
• Physical examination 
• Weight measurement 
• 12-lead ECG 
• Vital sign measurements 
• Concomitant medication and procedure monitoring 
• AE monitoring 
• Physiotherapeutic intervention(s) 
  
If repeat laboratory assessment results are within the allowable thresholds, and the patient has an 
unscheduled visit for SRP-5051 dosing within the designated 
 window, the following 
study procedures are to be performed as scheduled (Table 1):  
• Urine dipstick 
• QUA 
• Serum cystatin C assessment 
• Weight measurement 
• Vital sign measurements 
  
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• Plasma PK sampling (if applicable for the visit) 
If SRP-5051 dosing is postponed due to laboratory abnormalities, the dose may subsequently be 
administered outside the 
 window specified in the Schedule of Events (Table 1),  
provided that: 
• Repeat laboratory test results are within the allowable thresholds as per Section 9.3, and 
• No  doses of SRP-5051 
 are administered within 14 days. 
9.3. 
Safety Monitoring 
9.3.1. 
Safety Monitoring for Liver Chemistry Tests 
Liver chemistry tests are to be monitored as specified in the Schedule of Events (Table 1). Initial 
abnormal liver chemistry test result(s) are to be confirmed if: 
• GGT or GLDH or AST or ALT measurement is 
 × ULN (or 
 × Baseline value, if 
the Baseline value was  ULN) at any time during the study 
Patients with confirmed abnormal liver chemistry test results (as detailed immediately above) 
must have their liver chemistry (GGT, GLDH, ALT, AST, alkaline phosphatase [ALP], INR,  
and total bilirubin) retested 
. 
 
 if abnormalities stabilize, or if the study drug has been discontinued and the patient 
is asymptomatic. 
Stopping rules for liver chemistry test results are provided in Section 7.3.1. 
9.3.1.1. 
Additional Investigations for Liver Function 
For patients with confirmed abnormal liver chemistry test results (as detailed above in 
Section 9.3.1), it is recommended that the following additional evaluations be performed: 
 
 
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9.3.2. 
Safety Monitoring for Renal Function 
Renal tests are to be monitored as specified in the Schedule of Events (Table 1) and the renal 
monitoring decision trees provided in Figure 2 (local analysis) and Figure 3 (central analysis). 
Patients with the following test results must undergo repeat testing for confirmation of  
the abnormal results: 
• Protein 
 (dipstick) 
• Urinary protein to creatinine ratio (UPCR) 
 or 
 
• Urinary albumin to creatinine ratio (UACR) 
 or 
 
• Serum creatinine 
 above Baseline or 
 above Baseline 
• Serum creatinine 
 × ULN 
• Estimated glomerular filtration rate (eGFR) 
 
• RBCs 
/HPF 
• Elevated serum cystatin C > ULN 
Stopping rules for renal test results are provided in Section 7.3.2. 
9.3.2.1. 
Additional Investigations for Renal Function 
 urine collection is to be undertaken to quantify any proteinuria and GFR 
changes indicated by confirmed abnormal test results, as detailed above in Section 9.3.2. 
Additional evaluations—including nephrology consultation, renal ultrasound/CT/MRI, and renal 
biopsy—may be performed at the discretion of the Investigator, in consultation with the Sponsor 
Medical Monitor.
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9.3.3. 
Safety Monitoring for Hypersensitivity 
Patients will be monitored for the occurrence of allergic reactions or complement-mediated 
reactions primarily via monitoring of AEs, as specified in the Schedule of Events (Table 1). 
Patients will be instructed to promptly report any signs or symptoms of fever or constitutional 
symptoms that may arise during the study, and the Investigator must closely evaluate all 
potential causes, including concomitant illness. In addition to monitoring of AEs, routine 
laboratory monitoring for complement-mediated reactions
 
will be performed as outlined in the Schedule of Events (Table 1). 
Stopping rules for hypersensitivity AEs are provided in Section 7.3.3. 
9.3.3.1. 
Additional Investigations for Hypersensitivity 
Patients who experience significant or persistent constitutional symptoms (as detailed above in 
Section 9.3.3) are to discuss these symptoms with the Sponsor Medical Monitor to determine 
whether additional monitoring or laboratory tests are required. Additional evaluations—
including 
 
 
may be performed at the discretion of the 
Investigator, in consultation with the Sponsor Medical Monitor. 
9.3.4. 
Safety Monitoring for Platelet Count Results 
Platelet count is to be monitored as specified in the Schedule of Events (Table 1). 
Patients who have a confirmed occurrence of platelets 
 must have the following 
evaluations performed: 
Stopping rules for platelet count results are provided in Section 7.3.4. 
9.3.4.1. 
Additional Investigations for Platelet Count 
Additional platelet evaluations for confirmed, unexplained, and significant platelet count 
reductions (as detailed above in Section 9.3.4 )—including 
 
 
— 
may be performed at the discretion of the Investigator, in consultation with the Sponsor  
Medical Monitor. 
 
 
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9.3.5. 
Safety Monitoring for Rhabdomyolysis 
Monitoring for rhabdomyolysis must occur through urine dipstick and monitoring of AEs, as 
specified in the Schedule of Events (Table 1). 
Patients with confirmed heme+ dipstick urinalysis are to be evaluated for urine microscopy and 
for the following AEs: 
• Rhabdomyolysis 
• Acute onset or exacerbation of myalgia 
• Myoglobinuria 
• Chromaturia (eg, tea-colored urine) 
There are no applicable stopping rules for rhabdomyolysis. 
9.3.5.1. 
Additional Investigations for Rhabdomyolysis 
In the event of any of the AEs detailed above in Section 9.3.5, patients must undergo evaluations 
of myoglobinuria, CK, renal function (eg, serum cystatin C), and serum chemistry 
 
 until values reach usual/pre-event levels or stabilize. 
In addition, Investigators are to obtain a more detailed history of symptoms, preceding activity 
and hydration status, concomitant drug use, and recent or concurrent infection(s). 
Additional evaluations, 
 
, may be performed at the discretion of the Investigator, in consultation with the 
Sponsor Medical Monitor. 
9.4. Randomization and Blinding 
This study is open-label. No randomization will be performed. Neither the patient, the patient’s 
parent(s)/caregiver(s), nor study personnel will be blinded to study drug. 
9.5. Prior and Concomitant Medications 
No other medications may be administered concomitantly during the infusion of SRP-5051. 
The following therapies are not permitted during the conduct of this study: 
• Treatment with any other exon-skipping therapy or any experimental gene therapy for 
the treatment of DMD. 
• Immunosuppressants (other than oral or systemic corticosteroids) 
• Systemic aminoglycoside antibiotic or statin 
• Since entering a study administering SRP-5051, initiation or change of dosing (except 
for modification to accommodate changes in weight or changes in standard of care) 
for ACE inhibitors, ARB agents, β-blockers, potassium, herbal/nonherbal 
supplements, vitamins, minerals, or homeopathic preparations. 
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• Medications that can increase the risk of bleeding in the Investigator’s opinion (eg, 
anticoagulants, antiplatelet agents, novel oral anticoagulants, selective norepinephrine 
reuptake inhibitors, etc.). 
• Anti-arrhythmic therapies, diuretics, and any herbal medication/supplement 
containing aristolochic acid are prohibited during the trial. 
The dosage of any medication should be constant for at least 4 weeks prior to Day 1 and 
throughout the study, unless clinically indicated. 
The Investigator is to contact the Medical Monitor if he/she is unsure about changing a specific 
medication, or is uncertain if an herbal medicine/supplement contains aristolochic acid. 
Any medication taken by a patient during the course of the study, the reason for its use (ie, 
indication), and any modification to the dose of that medication and the reason for the 
modification (ie, corresponding indication) will be documented in the source documents and the 
electronic case report form (eCRF). 
9.6. Treatment Compliance 
All doses will be administered under the direct supervision of trained staff. 
The study staff will maintain an ongoing record of the dispensing and administration of the study 
drug for each patient via an accountability record or equivalent document. 
Accurate recording of each study drug administration will be made in the appropriate section of 
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10. 
STUDY ASSESSMENTS 
10.1. 
Safety Assessments 
10.1.1. 
Adverse Events 
The collection of AEs is detailed in Section 11.2. 
10.1.2. 
Vital Sign Measurement, Weight, and Height 
Vital sign measurements (including blood pressure, heart rate, respiration, and oral temperature), 
height and ulnar length, and weight will be obtained at the time points specified in the Schedule 
of Events (Table 1). 
During infusion of study drug, vital signs will be collected from the contralateral arm from which 
the blood samples are collected. Vital sign measurements will be monitored approximately 
 prior to infusion, and approximately 
 after the end of the 
infusion and then approximately every 
 thereafter up to 
 after the end of  
the infusion. In the absence of either a) IRRs (whether local or systemic) or b) other symptoms or 
signs of hypersensitivity associated with drug administration following  consecutive SRP-5051 
administrations at the same dose level, collection of vital signs beyond 
 post-end of 
infusion is not required. 
All measurements of vital signs will be performed after the patient has remained inactive for at 
least 
. Pulse rate and respiratory rate are to be measured over 
. For patients 
who are able to reach the supine position, blood pressure and pulse rate are to be measured after 
the patient has been supine for at least 
. For patients who are unable to reach the supine 
position, blood pressure and pulse rate are to be measured with the patient in a consistent 
position throughout the study. 
When vital sign measurements are scheduled at the same time as blood draws (
 prior 
to the infusion), the blood draw will be obtained at the scheduled time point, and the vital signs 
will be measured prior to, but as close to, the scheduled blood draw as possible. 
Temperature is to be recorded in degrees Celsius (°C) and weight is to be recorded in kilograms. 
10.1.3. 
Physical Examination 
Full physical examinations and limited physical examinations will be performed by the 
Investigator or qualified study staff at the applicable time points specified in the Schedule of 
Events (Table 1). 
Full physical examinations will include examination of general appearance, head, ears, eyes, 
nose, throat, heart, chest (respiratory), abdomen (gastrointestinal), skin, lymph nodes, 
extremities, musculoskeletal, and neurological systems and will be performed 
  
 thereafter. Limited physical examinations will include cardiac, 
pulmonary, abdominal, and symptom-directed examination, and are to be performed 
 
. 
 
 
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10.1.4. 
Clinical Laboratory Tests 
The following routine clinical laboratory tests will be performed at the time points specified in 
the Schedule of Events (Table 1); refer to Section 10.1.4.1 below for instructions regarding 
unscheduled laboratory assessments. Clinical laboratory tests will be collected at the study site or 
at another convenient location, and will be analyzed centrally. 
Routine clinical laboratory tests will be processed according to the Laboratory Manual provided 
for the study and will be analyzed by an accredited central laboratory selected by the Sponsor. 
Samples that are to be collected during dosing visits, as specified in the Schedule of Events 
(Table 1), will be collected prior to the study drug infusion, and may be obtained up to  
 prior to the infusion. 
Chemistry: 
Sodium, chloride, potassium, calcium, glucose, creatinine, blood urea 
nitrogen, albumin, uric acid, total bilirubin, ALP, amylase, ALT, AST, 
GLDH, GGT, lactate dehydrogenase, C-reactive protein, and  
creatine kinase  
Hematology: 
RBCs, total WBCs, hemoglobin, hematocrit, neutrophils, lymphocytes, 
monocytes, eosinophils, basophils, and platelets 
Coagulation screen: Prothrombin time, international normalized ratio, and activated partial 
thromboplastin time 
QUA: 
pH, specific gravity, protein, glucose, ketones, cytology, and hemoglobin 
Renal biomarkers: 
 albumin, UACR/UPCR 
Other:  
eGFR, serum cystatin C, antiplatelet antibodies, serum complement, and 
 urine collection (including protein, albumin, and RBCs; at 
Baseline and again if required as per Section 9.3.2) 
Refer to the Laboratory Manual for information on normal ranges. 
Any value outside of the current reference ranges for the laboratory performing the test will be 
flagged on the laboratory results. The Investigator will determine whether abnormal assessment 
results are clinically significant or not clinically significant (as defined below in Section 10.1.5).  
Serum cystatin C, QUA, and complement testing will be obtained every 
. The first 
morning void will be used if possible. If serum cystatin C or QUA results are abnormal, 
unscheduled labs will be required and results reviewed prior to the next dose. Results must be 
reviewed and confirmed to meet the required thresholds prior to dosing at the subsequent visit, as 
described in Figure 3 and Section 9.3.2.  
Additionally, on infusion visits, a local urine dipstick will be performed and results assessed 
prior to dosing. Unscheduled local QUA will be performed if urine dipstick results are abnormal 
as defined in Figure 2. Unscheduled central QUA, serum cystatin C, and 
 urine collection 
may be required if QUA results are abnormal, as defined in Figure 3 and Section 9.3.2.  
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10.1.4.1. Unscheduled Laboratory Assessments 
Certain laboratory parameters may result in dosing delays, missed dose(s) (Section 9.2.2), or 
study drug discontinuation (Section 7.3). In the event of these abnormal laboratory results, 
additional safety laboratory assessment collections and monitoring are required.  
Before study drug dosing may resume, these unscheduled laboratory assessments may require 
the patient to complete additional visits, or to have additional laboratory assessments collected at 
the patient’s home or at another convenient location, for any or all of the following: 
• Additional blood sample collection  
• Additional spot urine sample collection  
• 
 urine collection  
10.1.5. 
Designation of Clinical Significance  
A laboratory abnormality (Section 11.2.1) deemed clinically significant by the Investigator is to 
be recorded as an AE. A clinically significant abnormality is generally an abnormality, 
confirmed by repeat testing, that is changed sufficiently from Screening/Baseline so that, in the 
judgment of the Investigator, a change in management is warranted. 
10.1.6. 
Electrocardiogram 
A 12-lead ECG will be obtained in triplicate at the time points specified in the Schedule of 
Events (Table 1) and reviewed centrally. These ECGs will be performed at a consistent time of 
day throughout the study and before any invasive procedures (eg, blood sampling or study drug 
infusion). 
 
 
 
  
The Investigator will review the ECG results and determine if the findings are  
clinically significant. 
10.1.7. 
Concomitant Medications, Procedures, and Therapies  
Concomitant medications and procedures, changes in the dosage of concomitant medications, 
and concomitant therapies, including physiotherapeutic interventions, will be reviewed and 
recorded at each visit from the time the patient signs the informed consent form.  
Refer to Section 9.5 for information about prohibited concomitant medications. 
10.2. 
Pharmacokinetic Assessments 
10.2.1. 
Blood Sample Collection 
Plasma samples will be obtained at the time points specified in the Schedule of Events (Table 1), 
and are to be collected via peripheral venipuncture from the contralateral arm used for drug 
infusion. Plasma PK samples may not be collected from an IVAD. 
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Refer to the Laboratory Manual for additional details on handling and processing of  
plasma samples. 
 
 
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11. 
ADVERSE EVENTS AND OTHER SAFETY INFORMATION 
11.1. 
Definitions 
11.1.1. 
Adverse Event  
An AE is any untoward medical occurrence in a clinical trial participant that does not necessarily 
have a causal relationship with the IP. An AE can, therefore, be any unfavorable and unintended 
symptom, sign, disease, condition, or test abnormality that occurs during or after administration 
of an IP, whether or not considered related to the IP. 
Adverse events include: 
• Symptoms described by the patient or signs observed by the Investigator or medical staff 
• The onset of new illness and the exacerbation of pre-existing medical conditions 
• Test abnormalities (laboratory tests, ECG, X-rays, etc.) deemed clinically significant  
(refer to Section 10.1.5 regarding designation of clinical significance)  
Abnormalities present at Screening are considered AEs only if they re-occur after resolution or 
worsen during the AE collection period. 
11.1.2. 
Serious Adverse Event  
An SAE is defined as any AE that results in any of the following: 
• Death: The patient died as the result of the event. 
• Life-threatening event: Any AE that places the patient, in the view of the Investigator or 
Sponsor, at immediate risk of death from the AE as it occurred (ie, does not include an 
AE that, had it occurred in a more severe form, might have caused death) 
• Required or prolonged inpatient hospitalization: The AE resulted in hospitalization or 
prolonged an existing hospitalization.  
o Hospitalizations that are part of the study procedures are exempt unless the 
hospitalization is prolonged (based on the judgment of the Investigator) due to 
 an event. 
o Pre-planned hospitalizations are not considered SAEs unless prolonged due to  
an AE. 
• Persistent or significant disability/incapacity: An AE that results in persistent or 
significant disability or disruption of a person’s ability to conduct normal life functions. 
• Congenital anomaly/birth defect: A congenital anomaly/birth defect that occurs in the 
offspring of a patient exposed to the study drug, or the partner of a patient exposed to the 
study drug. 
 
 


 
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• Important medical event: Medical and scientific judgment should be exercised in 
deciding whether other situations should be considered serious, such as important 
medical events that might not be immediately life-threatening or result in death or 
hospitalization, but might jeopardize the patient or might require intervention to prevent 
one of the other outcomes listed in the definition above. 
11.1.3. 
Adverse Events of Special Interest  
The AESIs in this study are defined below in Sections 11.1.3.1 through 11.1.3.5, and are to be 
reported as instructed in Section 11.4.2.5. Refer to Section 9.2.2.1 for guidance on study drug 
dose interruption/delay in patients who meet certain laboratory criteria, and to Section 7.3 for the 
study stopping rules. 
11.1.3.1. 
AESI Criteria for Liver Test Results 
11.1.3.2. 
AESI Criteria for Renal Test Results 
11.1.3.3. AESI Criteria for Hypersensitivity 
11.1.3.4. AESI Criteria for Platelet Count Results 
11.1.3.5. AESI Criteria for Rhabdomyolysis 
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11.1.4. 
Overdose 
An overdose is defined as administration of a quantity of a medicinal product given (per 
administration or cumulatively) that is above the maximum recommended dose according to the 
authorized product information. Refer to Section 11.4.2.2 for specific guidance on overdose as it 
pertains to SRP-5051. 
11.1.5. 
Medication Error 
A medication error is any preventable incident that may cause or lead to inappropriate study drug 
use or patient harm while the study drug is in the control of the healthcare professional or, in 
certain cases, the patient. Such incidents may be due to healthcare professional practice, product 
labeling, packaging and preparation, procedures for administration, and systems, including the 
following: prescribing, order communication, dispensing, nomenclature, compounding, 
distribution, administration, education, monitoring, and use. 
11.1.6. 
Accidental/Occupational Exposure 
Accidental/occupational exposure is the unintentional exposure to a study drug as a result of 
one’s professional or nonprofessional occupation, or accidental exposure to a nonprofessional to 
whom exposure was not intended (eg, study drug given to wrong patient). 
11.2. 
Collection of Adverse Events 
All AEs, regardless of the source of identification (eg, physical examination, laboratory 
assessment, ECG, reported by patient), must be collected and documented in the eCRF.  
All AEs will be collected and recorded from the time of informed consent/assent through the last 
follow-up visit.  
All AEs and SAEs experienced by a patient, irrespective of the suspected causality, will be 
monitored until the AE or SAE has resolved, any abnormal laboratory values have returned to 
Baseline or normal levels, the event has stabilized and there is a satisfactory explanation for the 
changes observed, the patient is lost to follow-up, or the patient has died. 
All AEs will be followed until the resolution of the AE, completion of the patient’s study 
participation, or study termination, whichever occurs first. All SAEs will be followed until 
resolution or until the condition stabilizes or returns to Baseline status. 
Concomitant illnesses that existed before entry into the study will not be considered AEs unless 
the illness recurs after resolution or worsens during the treatment period. Pre-existing conditions 
will be recorded in the eCRF, as well as on the SAE Report Form’s medical history section. 
Patients who have received at least 1 dose of study drug and are withdrawn from treatment 
(Section 8.6) will be asked to complete an Early Termination visit (to complete the EOS 
assessments) approximately 
 after their last dose of SRP-5051, or within  
 of a withdrawal decision if early termination occurs after a missed dose. Any AEs are to 
be recorded through the EOS/Early Termination Visit.  
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For patients who are found to be ineligible for the study during the Screening Period and are not 
enrolled (ie, screen failures), only SAEs (Section 11.1.2) will be reported (Section 11.4.1). 
If, at any time after the patient has completed participation in the study (Section 8.4), the 
Investigator or study staff becomes aware of an SAE that the Investigator assesses as related to 
the study drug (Section 11.3.1) or related to a study procedure (Section 11.3.2), then the event 
and any known details must be reported promptly to the Sponsor, no later than within  
24 hours of awareness. 
11.2.1. 
Clinical Laboratory Abnormalities 
A laboratory abnormality deemed clinically significant (Section 10.1.5) by the Investigator is to 
be recorded as an AE. Whenever possible, the underlying medical diagnosis (eg, anemia) is to be 
recorded as the AE term. Repeated additional tests and/or other evaluations required to establish 
the significance and etiology of an abnormal result is to be obtained when clinically indicated. 
11.2.2. 
Reporting Disease Progression 
The event of disease progression is not to be reported as an AE in this study. If AEs/SAEs occur 
in relation to disease progression, the AEs/SAEs must be reported per the AE/SAE reporting 
requirements described in this section. 
11.3. 
Classification of Adverse Events 
All AEs, whether serious or nonserious, will be classified by the Investigator according to the 
following rules and definitions. 
11.3.1. 
Relationship to Investigational Product 
For each AE, the Investigator will determine whether there is a reasonable likelihood that the AE 
may have been caused by the study drug, according to the categories below: 
Unrelated: 
There is no reasonable possibility that the event is related to 
the investigational drug product. 
Related: 
There is a reasonable possibility that the event is related to the 
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11.3.2. 
Relationship to Study Procedures 
For each AE, the Investigator will determine whether there is a reasonable possibility that the AE 
may have been caused by the study procedures, according to the categories below: 
Unrelated: 
There is no reasonable possibility that the event is related to 
the study procedures. 
Related: 
There is a reasonable possibility that the event is related to the 
study procedures.  
11.3.3. 
Relationship to Underlying Disease 
For each AE, the Investigator will determine whether there is a reasonable possibility that the AE 
may be related to the underlying disease, according to the categories below: 
Unrelated: 
There is no reasonable possibility that the event is related to 
the underlying disease. 
Related: 
There is a reasonable possibility that the event is related to the 
underlying disease. 
11.3.4. 
Severity of Adverse Events 
The Investigator is to assess the severity of all AEs using the National Cancer Institute 
Common Terminology Criteria for Adverse Events (CTCAE) scale, Version 5.0.  
Events not listed in the CTCAE are to be assessed according to the following scale: 
Grade 1:  
 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2:  
 
Moderate; minimal, local or non-invasive intervention 
indicated; limiting age-appropriate instrumental activities of 
daily living (ADL). 
Grade 3:  
 
Severe or medically significant but not immediately  
life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; limiting self-care ADL. 
Grade 4:  
 
Life-threatening consequences; urgent intervention indicated. 
Grade 5:  
 
Death related to AE. 
Note that “severity” is not the same as “seriousness”, which is defined in Section 11.1.2 
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In addition, laboratory or vital sign-based abnormalities that are defined as Grade 4 in the 
CTCAE solely by laboratory or vital sign measurements are not automatically clinically  
life-threatening; the Investigator must make this clinical assessment, regardless  
of grade. 
11.3.5. 
Outcome of Adverse Events 
“Outcome” describes the status of the AE. The Investigator will provide information regarding 
the patient outcome for each AE. Outcome categories will include “recovered”, “recovered with 
sequelae”, “not recovered”, “fatal”, and “unknown”. 
11.3.6. 
Action Taken Regarding the Investigational Drug Product 
The Investigator will provide information regarding the action taken with respect to the study 
drug in response to the AE. Categories for action taken regarding study drug will include “none”, 
“drug interrupted”, “drug withdrawn”, and “not applicable”. 
11.3.7. 
Expectedness of Adverse Events 
The expectedness of all AEs will be determined by the Sponsor according to the most recent 
version of the SRP-5051 Investigator’s Brochure.  
11.4. 
Recording Adverse Events 
All AEs from the time of providing signed informed consent/assent through the last follow-up 
visit will be recorded in each enrolled patient’s eCRF. All SAEs will also be recorded on the 
SAE form and reported to the Sponsor within 24 hours of awareness. Other safety information, 
such as that pertaining to special situations (Section 11.4.2) and specified AESIs 
(Section 11.1.3), will also be recorded on the specified forms for reporting to the Sponsor within 
24 hours of awareness. 
Information recorded is to include the following: a concise description of the event; date of event 
onset and resolution; determination of seriousness, severity, corrective treatment, outcome, and 
relationship to IP, study procedure, and underlying disease; and any action taken. Resolution 
occurs when the patient has returned to the Baseline state of health, or when further improvement 
or worsening of the event is not expected. 
Whenever possible, a diagnosis will be recorded as an AE, rather than symptoms or isolated 
laboratory abnormalities related to that diagnosis. Several symptoms or laboratory results that are 
associated with the same diagnosis can thus be part of the same AE. A medical or surgical 
procedure is not an AE; rather, the condition leading to the procedure is to be recorded as  
the AE.  
Similarly, death is not an AE, but rather, the outcome of the AE(s) that resulted in death. If the 
AE(s) leading to death are not known, then “death” must be reported as an AE.  
All causes of death are SAEs. In the event of death, every effort is to be made to obtain a death 
certificate and if possible, an autopsy report. If the cause of death is unknown, death will be 
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Any SAE assessed as related to the study drug, occurring after the patient completes the study, 
should be recorded on an SAE form and reported as per the instructions for SAEs provided  
immediately below. 
11.4.1. 
Reporting Serious Adverse Events 
11.4.1.1. Serious Adverse Events 
The Investigator must report all SAEs via email to
 within 24 hours of 
becoming aware of the initial SAE or any follow-up information regarding the SAE, as per the 
information printed on the SAE form and in the SAE Completion guideline. 
11.4.1.2. Suspected Unexpected Serious Adverse Reactions (SUSARs) 
All SUSARs will be handled by appropriate Sponsor (or designee) personnel and reported within 
the required timelines, in an unblinded fashion, to regulatory authorities and the IRB/IEC, per the 
requirements of the concerned competent authorities.  
11.4.2. 
Reporting Special Situations 
11.4.2.1. Pregnancy 
Females have not been included in clinical trials of SRP-5051, and pregnant and/or lactating 
women have not been dosed with SRP-5051.  
Patients in this study must follow the contraceptive requirements as outlined in Inclusion 
Criterion #3 (Section 8.2). If the female partner of a treated male patient becomes pregnant, the 
male patient must notify the Investigator within 24 hours of learning of the pregnancy. The 
Investigator must make every effort to ensure that the pregnant female is aware of the need to 
notify her healthcare provider regarding her male partner’s participation in this clinical trial and 
his potential exposure to SRP-5051. 
The study site staff must complete a pregnancy form and send to the Sponsor via email to 
 within 24 hours of learning of the pregnancy. The study site staff will make 
every effort to follow the pregnancy until the outcome is known. 
11.4.2.2. Overdose 
Currently, there is no basis for determining a clinically meaningful definition of overdose for 
SRP-5051. Therefore, as a preliminary criterion, an overdose is defined as administration of a 
dose 
 higher than the assigned dose per the protocol. For dose-calculation guidance, refer 
to the study-specific Pharmacy Manual. 
An overdose is not an AE. An overdose must be reported even if it does not result in an AE. An 
overdose must be recorded on the appropriate form and sent to the Sponsor via email to 
 within 24 hours. 
11.4.2.3. Medication Error  
Any medication error is to be reported to the Sponsor on a specialized form sent via email to 
within 24 hours of becoming aware, according to the process for reporting 
SAEs (Section 11.4.1). 
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11.4.2.4. Accidental/Occupational Exposure 
Any accidental/occupational exposure (Section 11.1.6) is to be reported to the Sponsor on a 
specialized form sent via email to 
within 24 hours of becoming aware, 
according to the process for reporting SAEs (Section 11.4.1). 
11.4.2.5. Adverse Events of Special Interest 
All AESIs (Section 11.1.3 ) are to be reported on the appropriate form and sent to the Sponsor 
via email to 
 within 24 hours, according to the same guidance provided in 
Section 11.4.1 for reporting SAEs. 
11.4.3. 
Miscellaneous 
11.4.3.1. Unblinding Due to a Medical Emergency 
Not applicable; this is an open-label study.  
11.4.3.2. Responsibilities of the Investigator 
The responsibilities of the Investigator include, but are not limited to, the following: 
• Monitoring and recording all AEs 
• Determining the seriousness, severity, and relationship to IP, study procedure, and 
underlying disease for each AE 
• Determining the onset and end date of each event 
• Providing the initial report of all SAEs, special situations, and noted AESIs to the 
Sponsor or designee within 24 hours of first knowledge  
• Providing follow-up information on SAEs in a timely and proactive manner 
• Responding to queries regarding AEs and SAEs in a timely manner 
• Ensuring that source documentation for all AEs is accurate and complete 
• Ensuring that the study is conducted as defined in this protocol 
Investigators may also report improvement of pre-existing DMD conditions or unexpected 
therapeutic responses. 
11.4.3.3. Responsibilities of the Sponsor 
The responsibilities of the Sponsor include, but are not limited to, the following: 
• Training of Investigator on AE/SAE and AESI definitions, safety assessments, and site 
obligations related to safety monitoring and reporting of AEs/SAEs 
• Training with regard to the accurate and legal reporting of SAEs to all applicable 
regulatory authorities, IRBs/IECs, clinical study sites, and other parties, as appropriate 
and required within the regulated timing 
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12. 
DATA COLLECTION, QUALITY ASSURANCE,  
AND MANAGEMENT 
12.1. 
Recording of Data 
Clinical data for this study will be captured in an electronic format. Electronic data capture will 
be provided by a contract research organization. The Investigator, or personnel delegated by the 
Investigator, will perform primary data collection/perform assessments based on the protocol 
design and capture in source documentation. Source documents are filed at the Investigator’s 
site. All required study information must be recorded on the appropriate CRF screens/forms 
using the CRF Help Text. An eCRF must be completed for each patient that is enrolled. Data 
entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents, or the discrepancies must be explained. The study monitor will conduct 100% 
source data verification to ensure maximum data integrity. All data must be carefully entered in a 
timely fashion to permit meaningful interpretation and study oversight. 
12.2. 
Quality Assurance 
The eCRFs will be reviewed at regular intervals by a clinical monitor from the Sponsor or a 
representative of the Sponsor per the agreed-upon Clinical Monitoring Plan against the source 
documentation for identification and clarification of any discrepancies. The Investigator must 
maintain accurate documentation (source data) that supports the information entered in the 
eCRF. Automated and manual quality checks will be in place to identify discrepancies, such as 
missing data, protocol deviations, out-of-range data, other data inconsistencies, and compliance. 
Requests for data clarification or correction will be documented as electronic queries within the 
eCRF and for the Investigator or site staff to resolve. All changes to the eCRFs will be tracked  
in an electronic audit trail. Investigator Site Files will be reviewed for compliance throughout the 
study. 
Audits may be carried out by the Sponsor’s representatives, and inspections may be performed 
by IRBs/IECs or regulatory authorities before, during, or after the study. The Investigator will 
allow and assist the Sponsor’s representatives and any regulatory agency to have direct access to 
all study records, eCRFs, patient medical records, and other source documentation, IP dispensing 
records and IP storage area, study facilities, and any other source documentation.  
The Investigator must make study files and data accessible to the study monitor, to other 
authorized representatives of the Sponsor, and to the appropriate regulatory authority inspectors. 
12.3. 
Retention of Study Documents 
At study completion, all eCRF data for an individual site will be copied onto a compact disc and 
provided to the Investigator for retention in the Investigator Site Files.  
The length of storage of study documents varies by country and stage of clinical development in 
any region in the world. Therefore, no study documents, including patient records and other 
source data, will be destroyed or moved to a new location without prior written approval from  
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If the Investigator relocates, retires, or withdraws from the clinical study for any reason, all 
records that are required to be maintained for the study are to be transferred to an agreed-upon 
designee.  
If offsite archiving is used, all records must be retrieved and made available for review at the 
time of an audit or regulatory authority inspection. 
 


 
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13. 
STATISTICS 
This section outlines the statistical analysis strategy and procedures for the study. Details of the 
statistical methods will be described in a separate technical document or in the Statistical 
Analysis Plan (SAP).  
13.1. 
Analysis Endpoints 
The study endpoints for evaluation are listed in Section 6.2. 
13.2. 
Analysis Sets 
The following analysis sets will be used for the primary and secondary endpoints in this study: 
• Safety Set: The Safety Set is defined as all patients who enroll in the study and have 
started the study drug (SRP-5051) infusion. The dose group will be designated according 
to the actual dose received. This analysis set will be used for the safety analyses. 
• PK Set: The PK Set is defined as all patients who enroll in the study, have started the 
study drug (SRP-5051) infusion, and have at least 1 PK concentration data collection. 
This analysis set will be used for the PK analyses.  
The analysis sets be used for other endpoints and/or additional analyses will be defined in  
the SAP. 
13.3. 
Statistical Methods 
This section describes the statistical methods that address the primary and secondary objectives 
of the study. 
 
 
13.3.1. 
Safety Analyses 
13.3.1.1. Adverse Events 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  
All AEs will be classified as treatment-emergent AEs (TEAEs) or non-TEAEs. A TEAE is 
defined as an AE that emerges during treatment, having been absent pre-treatment, or worsens 
relative to the pre-treatment state. An AE that does not meet the TEAE definition will be 
classified as a non-TEAE.  
Treatment-emergent AEs will be summarized using the number and percentage of patients 
reporting AEs, by MedDRA System Organ Class (SOC) and preferred term (PT), for each dose 
level and for the overall Safety Set. The ordering of AEs will be based on the AE rate in the 
overall Safety Set. 
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In general, summaries will have AEs categorized into all TEAEs and treatment-related TEAEs. 
Treatment-related TEAEs will be defined as those that the Investigator considers to be related to 
the study drug (Section 11.3.1). 
The following summary tables will be produced: 
• TEAEs 
• TEAEs by severity 
• Treatment-related TEAEs 
• Treatment-related TEAEs by severity 
• SAEs 
• AESIs 
• AEs leading to study drug discontinuation 
• AEs leading to death 
The following listings will be produced: 
• All TEAEs 
• Non-TEAEs 
• SAEs 
• AESIs 
• AEs leading to study drug discontinuation  
• AEs leading to death  
13.3.1.2. Other Safety Assessments 
Clinical laboratory tests, vital signs, ECGs, weight and height, and any other procedures that are 
performed routinely as part of standard of care (eg, annual echocardiogram), as applicable, will 
be summarized descriptively. Additional details will be provided in the SAP. 
13.3.1.3. Prior and Concomitant Medications 
Prior and concomitant medications will be coded by PT using the most recent World Health 
Organization Drug Dictionary (WHODrug) version. The number and percentage of patients in 
the Safety Set with concomitant medications will be tabulated by Anatomical Therapeutic 
Chemical classification pharmacological subgroup and WHODrug PT by dose level.  
At each level of summarization, a patient will be counted once if 1 or more medications at that 
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13.3.2. 
Pharmacokinetic Analyses 
For all patients in the PK Set, plasma concentrations at predose, Cmax (end of infusion), and 
approximately 4 to 6 hours postdose will summarized descriptively. Plasma concentration data 
may be evaluated and combined with clinical PK data from other clinical studies of SRP-5051. 
 
 
 
13.3.3. 
Summaries of Demographics, Baseline Characteristics, and Other Analyses 
13.3.3.1. Patient Disposition, Demographics, and Baseline Characteristics 
The number and percentage of patients completing or prematurely discontinuing from the study 
will be summarized. Reasons for premature discontinuation will also be summarized. 
Demographic characteristics, including age (years), race, and ethnicity; Baseline characteristics, 
including height (cm), weight (kg), and body mass index (kg/m2); 
 
 
13.4. 
Interim Analysis 
No formal interim analysis is planned. 
13.5. 
Sample Size 
The sample size for this LTE study will be determined by the number of patients who participate 
in other studies administering SRP-5051. Up to 60 patients are planned to enroll in this study 
upon completing a Phase 1 (ie, the completed Study 5051-101 [Section 5.4.1.1]) or Phase 2 (eg, 
the ongoing Study 5051-201 [Section 5.4.2.2]) study of SRP-5051
 
 
 
 
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14. 
ETHICS AND OTHER SPECIAL REQUIREMENTS 
14.1. 
 Compliance with Ethical and Regulatory Guidelines 
This study will comply with the ethical and scientific principles governing clinical research as set 
out in the Declaration of Helsinki, ICH E6 (R2) GCP Guideline, and applicable national 
regulations such as the European Clinical Trial Directive 2001/20/EC, European Union Clinical 
Practice Directive 2005/28/EC, and principles of GCP described in 21 Code of Federal 
Regulations parts 50, 54, 56, and 312. 
14.2. 
Institutional and Ethics Review 
Before enrollment of patients into the study, the protocol and informed consent (for study 
participants or parents/legal guardians, if applicable ) and informed assent (for patients, if 
applicable) documents will be reviewed and approved by the appropriate IRB/IEC and regulatory 
authority. Amendments to the protocol and all substantial changes to the trial documentation will 
be subjected to the same IRB/IEC and regulatory authority review requirements as the original 
study protocol.  
The Investigator will promptly notify the IRB/IEC and Sponsor of any SAEs or of any other 
information that might affect the safe use of the IP during the study. Institutional Review Board 
approvals/IEC positive opinions and regulatory authorities’ approvals must be sent to the 
Sponsor, or its designee, before initiation of the study or before an amendment is instituted.  
All correspondence with the IRB/IEC and the regulatory authority must be retained in the study 
regulatory files.  
14.3. 
Informed Consent 
Informed consent from each patient’s parent(s) or legal guardian(s) and informed assent from 
each patient, if applicable, must be obtained before any study-specific Screening or Baseline 
Period evaluations are performed. One copy of the signed informed consent/assent documents 
will be given to the patient; the Investigator will retain the original copies of these documents. 
The informed consent/assent documents, as prepared by the Sponsor (or designee), must be 
reviewed and approved by the IRB/IEC and regulatory authorities, as applicable, before initiation 
of the study.  
14.4. 
Compliance with the Protocol 
All processes and procedures defined in this protocol must be adhered to. Emergency departures 
from the protocol that eliminate an apparent immediate hazard to a particular patient, and are 
deemed by the Investigator as crucial for the safety and well-being of that patient, may be 
instituted for that patient only and documented as deviations. The Investigator will contact the 
Medical Monitor as soon as possible regarding such a deviation. These departures do not require 
pre-approval by the IRB/IEC; however, the IRB/IEC and Medical Monitor must be notified in 
writing as soon as possible in accordance with the IRB/IEC policies after the departure has  
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14.5. 
Confidentiality 
All information regarding the nature of the proposed investigation that is provided to the 
Investigator by the Sponsor, the Sponsor’s designee, or the study monitor, with the exception of 
information that is required by law or regulations to be disclosed to the IRB/IEC, the patient’s 
parent(s) or legal guardian(s), or the appropriate regulatory authority, must be kept in confidence 
by the Investigator in accordance with current global data protection standards (eg, Health 
Insurance Portability and Accountability Act, General Data Protection Regulation). 
Patients will be referenced by an assigned patient identification number on the eCRFs and other 
data collected by the Sponsor. The Investigator must maintain all documents related to the study 
that identify the patient (eg, the signed informed consent document) in strict confidence, except 
to the extent necessary to allow auditing by the appropriate regulatory authorities, the IRB/IEC, 
the study monitor, or the Sponsor or its representatives. 
 


 
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15. 
STUDY DOCUMENTATION AND GENERAL INFORMATION 
15.1. 
Essential Study Documents 
Essential study documents are among the critical documents required before study enrollment is 
to occur. Essential documents, such as the Investigator’s Brochure, study-specific Pharmacy 
Manual, and final protocol, must be kept onsite in a designated study site file.  
The study site files will also contain (including but not limited to) the following: patient study 
drug accountability records, study drug accountability (receipt/dispensing) records, 
Sponsor/Investigator correspondence, IRB/IEC documentation and correspondence, deviations, 
biological sample records, and SAE and Investigational New Drug (IND) safety reports/ 
Safety Alert Letters/SUSARs. 
15.2. 
General Information 
The Investigator should be familiar with and refer, as needed, to the current SRP-5051 
Investigator’s Brochure, along with subsequent Safety Alert Letters, the study-specific Pharmacy 
Manual, the Laboratory Manual, and all other study-specific information that is provided during 
the study initiation visit or throughout the duration of the study. 
15.3. 
Dissemination of Study Results 
The information that is developed during the conduct of this clinical study is considered to be 
strictly confidential. This information may be disclosed only as deemed necessary by the 
Sponsor. At the conclusion of this clinical study, a clinical study report will be prepared. In 
addition, a manuscript may be prepared for publication in a reputable scientific journal under the 
direction of the Sponsor. The Sponsor will publish and communicate the clinical study results, 
irrespective of positive or negative findings. Data generated for this study will be exclusively 
owned by the Sponsor, as detailed in the Clinical Trial Agreement. The study will be registered 
on ClinicalTrials.gov and to any other registries as required by law. After completion of the 
study, results will be disseminated through the applicable public website(s). 
15.4. 
Publication Policy 
All unpublished information given to the Investigator by the Sponsor shall not be published or 
disclosed to a third party without the prior written consent of the Sponsor. The primary 
publication from this study will report the results of the study in accordance with the current 
“Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in 
Medical Journals” (www.ICMJE.org). Publication of the results will occur in a timely manner 
according to applicable regulations.  
The publications committee established by the Sponsor will oversee this process. Additional 
publications may follow. Policies regarding the publication of the study results are defined in the 
Clinical Trial Agreement. 


 
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15.5. 
Product Handling and Complaints Reporting 
If there are any issues during the course of the study related to the quality of the IP, the 
Investigator, clinical site pharmacist, or pharmacy designee should contact the Sponsor or 
designated contract research organization. 


 
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16. 
LIST OF REFERENCES 
Beenakker EA, Fock JM, Van Tol MJ, et al. Intermittent prednisone therapy in Duchenne 
muscular dystrophy: a randomized controlled trial. Arch Neurol. 2005 Jan;62(1):128-32. 
Biggar WD, Harris VA, Eliasoph L, et al. Long-term benefits of deflazacort treatment for boys 
with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006 
Apr;16(4):249-55. 
 
 
Brooke MH, Fenichel GM, Griggs RC, et al. Duchenne muscular dystrophy: patterns of clinical 
progression and effects of supportive therapy. Neurology. 1989 Apr;39(4):475-81. 
Centers for Disease Control and Prevention (CDC). Prevalence of Duchenne/Becker muscular 
dystrophy among males aged 5-24 years – four states, 2007. MMWR Morb Mortal Wkly Rep. 
2009 Oct 16;58(40):1119-22. 
 
 
 
Eagle M, Baudouin SV, Chandler C, et al. Survival in Duchenne muscular dystrophy: 
improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. 
Neuromuscul Disord. 2002 Dec;12(10):926-9. 
Emery AE. Population frequencies of inherited neuromuscular diseases--a world survey. 
Neuromuscul Disord. 1991;1(1):19-29. 
Kohler M, Clarenbach CF, Bahler C, et al. Disability and survival in Duchenne muscular 
dystrophy. J Neurol Neurosurg Psychiatry. 2009;80(3):320-5. 
 
 
Manzur AY, Kuntzer T, Pike M, et al. Glucocorticoid corticosteroids for Duchenne muscular 
dystrophy. Cochrane Database Syst Rev. 2004;(2):CD003725. 
 
 
 
McMillan HJ, Gregas M, Darras BT, et al. Serum transaminase levels in boys with Duchenne 
and Becker muscular dystrophy. Pediatrics. 2011 Jan;127(1):e132-6. 
 
 
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imminent loss of ambulation. J Neurol. 2006 Oct;253(10):1309-16. 
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