Clinical trial NCT03406780
Conditions: Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Neuromuscular Diseases Nervous System Diseases Genetic Diseases, X-Linked Genetic Diseases, Inborn
Keywords: Duchenne Muscular Dystrophy Cell Therapy Performance of the Upper Limb Pulmonary Function Ambulatory Non-Ambulatory Glucocorticoids
Sponsor: Capricor Inc.
Start date: 2018-04-04; Completion date: 2020-03-10
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
HOPE-2 is a double-blind clinical trial evaluating the safety and efficacy of a cell therapy called CAP-1002 in study participants with Duchenne Muscular Dystrophy (DMD). Non-ambulatory and ambulatory boys and young men who meet eligibility criteria will be randomly assigned to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during a 12-month period.

Detailed description:
* Approximately 20 eligible study participants will be randomized to either CAP-1002 or placebo in a 1:1 ratio.
* The trial will include visits at Screening, Baseline/Day 1, Week 4, and Months 3, 6, 9, and 12 with IV infusions of CAP-1002 or placebo on Day 1 and Months 3, 6, and 9.
* Safety evaluations will include adverse events, concomitant medications, physical exam, vital signs, 12-lead ECG, and clinical laboratory testing.
* Efficacy will be evaluated by Performance of the Upper Limb, cardiac MRI, pulmonary function testing, North Star Ambulatory Assessment (ambulatory subjects only), strength testing, and quality of life.
* If trial data suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the recommendation of the Data Safety Monitoring Board (DSMB), will introduce an open-label extension study to offer CAP-1002 to study participants who were randomized to placebo and completed all trial visits during the 12-month period.

Arms: arm 1: Patients will receive 150 million Cardiosphere-derived Cells (CDCs) via intravenous infusion every 3 months for a total of 4 doses. arm 2: Patients will receive a placebo solution via intravenous infusion every 3 months for a total of 4 doses.
Interventions: intervention 1: CAP-1002 intervention 2: Placebo
Intervention descriptions: intervention 1: The active pharmaceutical ingredient in CAP-1002 is Cardiosphere-Derived Cells (CDCs). CDCs are known to secrete numerous bioactive elements (growth factors, exosomes) which impact the therapeutic benefits of the cell-based therapy. The mechanism of action is the composite ability to be immunomodulatory, anti-fibrotic, anti-inflammatory, and pro-angiogenic. intervention 2: Placebo

Protocol documents:
SAP_002.pdf: 
STATISTICAL ANALYSIS PLAN 
Protocol Number 
CAP-1002-DMD-02 
Trial Phase  
Phase 2  
Protocol Title 
A Phase 2, Randomized, Double-Blind, Placebo-
Controlled Trial Evaluating the Safety and Efficacy of 
Intravenous Delivery of Allogeneic Cardiosphere-
Derived Cells in Subjects with Duchenne Muscular 
Dystrophy (HOPE-2) 
Protocol Version 
Amendment 5.0, 27 September 2019 
Product Name or Number 
CAP-1002 Allogeneic Cardiosphere-Derived Cells 
Indication 
Duchenne Muscular Dystrophy 
Sponsor 
Capricor, Inc. 
8840 Wilshire Blvd., 2nd Floor 
Beverly Hills, CA 90211 
USA 
Document Type 
Statistical Analysis Plan 
Prepared by 
 
 
 
 
 
Version Number (Date) 
Final v. 3.0 (20 March 2020) 
This document is confidential and proprietary to Capricor, Inc. and its affiliates. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be reproduced, published, or otherwise disseminated or disclo sed or used 
without the prior written approval of Capricor, Inc. and its affiliates, except that this document may be disclosed in any medium to appropriate 
clinical Investigators, Institutional Review Boards, and others directly involved in the clinical investigation that is the subject of this 
information under the condition that they keep the information strictly confidential. 


STATISTICAL ANALYSIS PLAN 
 
Final v. 3.0 (20 March 2020) 
 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and 
Efficacy of Intravenous Delivery of Allogeneic Cardiosphere-Derived Cells in Subjects with 
Duchenne Muscular Dystrophy (HOPE-2) 
 
 
 
 
 
 
 


STATISTICAL ANALYSIS PLAN 
 
Final v. 3.0 (20 March 2020) 
 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and 
Efficacy of Intravenous Delivery of Allogeneic Cardiosphere-Derived Cells in Subjects with 
Duchenne Muscular Dystrophy (HOPE-2) 
 
 
 
 
 
 


STATISTICAL ANALYSIS PLAN 
 
Final v. 3.0 (20 March 2020) 
 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and 
Efficacy of Intravenous Delivery of Allogeneic Cardiosphere-Derived Cells in Subjects with 
Duchenne Muscular Dystrophy (HOPE-2) 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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REVISION HISTORY 
 
Version 
Date 
Summary of Revision(s) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term 
Explanation 
Term 
Explanation 
10MWRT 
10-Meter Walk/Run Time 
GGT 
Gamma-Glutamyl Transferase 
AE 
Adverse Event 
HLA 
Human Leukocyte Antigen 
ALT 
Alanine Aminotransferase 
IFR 
Inspiratory Flow Reserve 
AR(1) 
Auto-Regressive 
IL 
Interleukin 
AST 
Aspartate Aminotransferase 
IP 
Investigational Product 
ATC 
Anatomic Therapeutic 
Chemical 
ITT 
Intent-to-Treat 
BMI 
Body Mass Index 
IV 
Intravenous 
BSA  
Body Surface Area  
IWRS 
Interactive Web Response 
System 
BUN 
Blood Urea Nitrogen 
kg 
Kilograms 
CBC 
Complete Blood Count 
K-R 
Kenward-Roger 
CDC 
Cardiosphere-Derived Cells 
LV 
Left Ventricle / Left 
Ventricular 
CEC 
Clinical Events Committee 
M cells 
Million cells 
CK-MB 
Creatine kinase MB Isoenzyme 
MedDRA 
Medical Dictionary for 
Regulatory Activities 
CK-MM 
Creatine kinase MM Isoenzyme
MEP 
Maximum Expiratory Pressure 
CLIA 
Clinical Laboratory 
Improvement Amendments 
MFI 
Mean Fluorescence Intensity 
cm 
Centimeters 
MIP 
Mean Inspiratory Pressure 
CURE 
Circumferential Uniformity 
Ratio Estimate 
mITT 
Modified Intent-to-Treat 
CXCL10 
C-X-C Motif Chemokine 10 
MMRM 
Mixed-Model Repeated 
Measures 
DMD 
Duchenne Muscular Dystrophy 
MRI 
Magnetic Resonance Image 
DMD UL- PROM DMD Upper Limb Patient- 
Reported Outcome Measures 
NSAA 
North Star Ambulatory 
Assessment 
DMD-LMS 
DMD Lifetime Mobility Scale 
PCF 
Peak Cough Flow 
DSA 
Donor-Specific Antibody 
PEF 
Peak Expiratory Flow 
DSMB 
Data Safety Monitoring Board 
PFT 
Pulmonary Function Test 
ECG 
Electrocardiogram 
PI 
Primary Investigator 
FEV1 
Forced Expiratory Volume in 1 
Second 
PODCI 
Pediatric Outcomes Data 
Collection Instrument 
FVC 
Force Vital Capacity 
PP 
Per Protocol 


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Term 
Explanation 
Term 
Explanation 
PROM 
Patient-Reported Outcome 
Measure 
SpO2 
Peripheral Capillary 
Hemoglobin Oxygen 
Saturation 
PT 
Preferred Term 
SVC 
Slow Vital Capacity 
PUL 
Performance of the Upper 
Limb 
TEAE 
Treatment-Emergent Adverse 
Events 
RBC 
Red Blood Cell 
TLF 
Tables, Listings and Figures 
SAP 
Statistical Analysis Plan 
TNF-α 
Tumor Necrosis Factor Alpha 
SD 
Standard Deviation 
WBC 
White Blood Cell 
SOC 
System Organ Class 
WHODrug 
Global 
World Health Organization 
Drug Global Dictionary 
SOP 
Standard Operating Procedures 
 
 
 
 
 


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TABLE OF CONTENTS 
1 
STUDY OVERVIEW ..........................................................................................................9 
2 
STUDY OBJECTIVES AND ENDPOINTS .......................................................................9 
2.1 
Study Objectives ..............................................................................................................9 
2.1.1 Primary .........................................................................................................................9 
2.1.2 Secondary .....................................................................................................................9 
2.2 
Study Endpoints .............................................................................................................10 
2.2.1 Primary Safety Endpoint ............................................................................................10 
2.2.2 Secondary Safety Endpoints ......................................................................................10 
2.2.3 Primary Efficacy Endpoint.........................................................................................10 
2.2.4 Secondary Efficacy Endpoints ...................................................................................10 
2.2.5 Exploratory Efficacy Endpoints .................................................................................10 
3 
STUDY DESIGN...............................................................................................................11 
3.1 
Sample Size and Randomization....................................................................................12 
3.2 
Data Safety Monitoring Board .......................................................................................13 
3.3 
Interim Analyses ............................................................................................................13 
3.3.1 Interim Analysis .........................................................................................................13 
3.3.2 Interim Plus Analysis .................................................................................................13 
3.3.3 Interim Plus 2 Analysis ..............................................................................................13 
3.3.4 Interim Plus 3 Analysis ..............................................................................................14 
4 
GENERAL STRATEGIES FOR DATA PRESENTATION ............................................14 
4.1 
Treatment Groups ..........................................................................................................14 
4.2 
Study Day.......................................................................................................................14 
4.3 
Handling of Dropouts or Missing Data ..........................................................................15 
4.4 
Multiplicity ....................................................................................................................15 
4.5 
Analysis Populations ......................................................................................................15 
5 
STUDY POPULATION PARAMETERS .........................................................................16 
5.1 
Eligibility and Informed Consent...................................................................................16 
5.2 
Protocol Deviations ........................................................................................................16 
5.3 
Demographics and Baseline Characteristics ..................................................................17 
5.4 
Medical Status Questionnaire ........................................................................................17 
5.5 
General Medical History ................................................................................................17 


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5.6 
DMD Medical History ...................................................................................................17 
5.7 
Donor-Specific Antibodies ............................................................................................18 
5.8 
Physical Examination.....................................................................................................18 
5.9 
Prior and Concomitant Medications ..............................................................................18 
5.10 
Planned Medical/Surgical Procedures ...........................................................................19 
5.11 
IP Administration ...........................................................................................................19 
5.12 
Subject Study Progress...................................................................................................19 
5.13 
Subject Disposition ........................................................................................................19 
6 
EFFICACY ANALYSES ..................................................................................................19 
6.1 
Primary Efficacy Endpoint.............................................................................................19 
6.2 
Secondary Efficacy Endpoints .......................................................................................20 
6.3 
Exploratory Efficacy Endpoints .....................................................................................20 
6.3.1 PUL Scale ..................................................................................................................20 
6.3.2 Strength Testing .........................................................................................................21 
6.3.3 DMD Upper Limb PROM .........................................................................................21 
6.3.4 Pediatric Outcomes Data Collection Instrument........................................................21 
6.3.5 DMD Lifetime Mobility Scale ...................................................................................21 
6.3.6 North Star Ambulatory Assessment and 10-Meter Walk/Run Time .........................22 
6.3.7 Pulmonary Function Testing ......................................................................................22 
6.3.8 Cardiac MRI...............................................................................................................22 
6.3.9 Biomarkers .................................................................................................................23 
6.3.10 Resource Utilization...................................................................................................23 
7 
SAFETY ANALYSES.......................................................................................................23 
7.1 
Adverse Events ..............................................................................................................23 
7.1.1 Clinical Events Committee ........................................................................................23 
7.2 
Partner Reported Pregnancy...........................................................................................24 
7.3 
Laboratory Tests (Hematology, Serum Chemistry, and Urinalysis)..............................24 
7.4 
Vital Signs, Height, Weight and BMI ............................................................................24 
7.5 
12-Lead Electrocardiograms ..........................................................................................24 
8 
DEVIATIONS FROM STATISTICAL METHODS IN THE PROTOCOL ....................25 
9 
Appendices .........................................................................................................................26 
9.1 
APPENDIX A: Schedule of Assessments .....................................................................26 


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9.2 
APPENDIX B: Table of Contents – Interim Analysis Tables and Listings ..................30 
9.3 
APPENDIX C: Table of Contents – Interim Plus Analysis Tables and Listings ..........35 
9.4 
APPENDIX D: Table of Contents – Interim Plus 2 Analysis Tables and 
Listings ...........................................................................................................................38 
9.5 
APPENDIX E: Table of Contents – Interim Plus 3 Analysis Tables and 
Listings ...........................................................................................................................41 
9.6 
APPENDIX F: Table of Contents – Final Analysis Tables and Listings ......................44 
 
 
 


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1 
STUDY OVERVIEW 
Duchenne muscular dystrophy (DMD) is a severe, X-linked, progressive disease affecting 
approximately one in 3,600 to 9,200 male births caused by mutations in the dystrophin gene 
resulting in the absence of or non-functional dystrophin protein. 
DMD occurs in early childhood, with degeneration occurring progressively in the skeletal 
musculature and ultimately in the heart and respiratory muscles, resulting in premature death. 
Progressive weakness and muscle atrophy caused by degenerating muscle fibers begins in the 
lower extremities and pelvis before spreading into the upper extremities. Other symptoms 
include loss of some reflexes, a waddling gait, frequent falls, difficulty when rising from a sitting 
or lying position or when climbing stairs, changes to overall posture, and impaired breathing. 
Many children precipitously lose the ability to run or jump. The atrophied muscles, in particular 
the calf muscles, and less commonly, muscles in the buttocks, shoulders, and arms, may be 
enlarged by an accumulation of fat and connective tissue, causing them to look larger and 
healthier than they actually are (“pseudohypertrophy”). Bone thinning and scoliosis are common. 
Ultimately, a wheelchair becomes necessary, in most cases between 12 to 15 years of age.  
No pharmacologic or biological therapies proven to stop or reverse the progression of DMD have 
been approved in the US. Disease management consists primarily of preventive measures as well 
as active interventions to address the primary and secondary aspects of the disorder. 
CAP-1002 is intended to be used as a therapeutic to improve the morbidities associated with DMD 
and thus improve or prevent decline in muscle function through its composite immune-modulatory, 
anti-fibrotic, and regenerative mechanisms of action. 
 
 
 
 
 
 
2 
STUDY OBJECTIVES AND ENDPOINTS 
2.1 Study Objectives 
2.1.1 Primary  
To evaluate the safety and efficacy of intravenous CAP-1002 administered every three months in 
subjects with DMD and impaired skeletal muscle function.   
2.1.2 Secondary 
To evaluate the impact of repeated intravenous (IV) administrations of CAP-1002 on exploratory 
efficacy assessments of skeletal and cardiac muscle function, and quality of life. 


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2.2 Study Endpoints 
2.2.1 Primary Safety Endpoint 
The primary safety endpoints include the incidence of the following from baseline through the 
12-month timepoint: 
• Acute respiratory decompensation within 2 hours following Investigational Product (IP) 
administration 
• Hypersensitivity reaction 
− Hypersensitivity reaction is defined as a clinical syndrome including, but not limited 
to, fever, leukocytosis, or rash with onset ≤ 2 hours post infusion and lasting < 24 
hours, in the absence of clinical signs of concomitant infection.  
• All-cause mortality 
• Serious adverse events 
• Treatment-emergent adverse events related to IP or administration procedure 
• Immune sensitization syndrome 
− Immune sensitization syndrome shall be defined as: (a) clinical signs and symptoms 
consistent with systemic inflammation (e.g., fever, leukocytosis, rash, or arthralgia) 
with onset ≥ 24 hours post infusion and the absence of clinical signs of concomitant 
infection, AND (b) elevation of anti-human leukocyte antigen (HLA) antibodies 
against the donor cells [i.e., donor-specific antibodies (DSAs)], detected ≤ 30 days 
following onset of syndrome, of (i) ≥ 2000 mean fluorescent intensity (MFI) if 
baseline MFI ≤ 1000, or (ii) ≥ 2 times baseline otherwise 
2.2.2 Secondary Safety Endpoints 
The secondary safety endpoint is the incidence and severity of all adverse events (AEs) through 
the 12-month timepoint. 
2.2.3 Primary Efficacy Endpoint 
The primary efficacy endpoint is change from baseline to the 12-month timepoint in functional 
capacity as assessed by the mid-level (elbow) dimension of the PUL 1.2. 
2.2.4 Secondary Efficacy Endpoints 
The secondary efficacy endpoints include the change from baseline for the following: 
• Mid-level (elbow) dimension of the PUL 1.2 at Months 3, 6, and 9 (Month 12 is the 
primary endpoint). 
• Regional systolic left ventricular (LV) wall thickening as assessed by cardiac magnetic 
resonance imaging (MRI) at Months 6 and 12. 
2.2.5 Exploratory Efficacy Endpoints 
The exploratory efficacy endpoints include the change from baseline to each assessment 
timepoint for the following assessments: 
• All subjects 
− High-level (shoulder) dimension of the PUL 1.2 
− High-level (shoulder) dimension of the PUL 2.0 


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− Mid-level (elbow) dimension of the PUL 2.0 
− Distal-level (wrist and hand) dimension of the PUL 1.2 
− Distal-level (wrist and hand) dimension of the PUL 2.0 
− Grip strength 
− Key and tip-to-tip pinch strength 
− Elbow flexion strength 
− Slow vital capacity (SVC), forced expiratory volume in one second (FEV1), forced 
vital capacity (FVC), peak expiratory flow (PEF), maximum inspiratory pressure 
(MIP), maximum expiratory pressure (MEP), peak cough flow (PCF), and inspiratory 
flow reserve (IFR) 
− LV structure and function as assessed by cardiac MRI including ejection fraction, 
end-diastolic volume, end-systolic volume, stroke volume, regional wall thickness, 
and circumferential strain 
− Biomarkers may include those for muscle inflammation (osteopontin); systemic 
inflammation (interleukin 1 beta [IL-1ß], IL-2, -6 and -10; tumor necrosis factor alpha 
[TNF-α] and C-X-C motif chemokine 10 [CXCL10] ); muscle damage (troponin I 
[cardiac, fast skeletal, slow skeletal], troponin T, creatine kinase MM isoenzyme 
[CK-MM], creatine kinase MB isoenzyme [CK-MB], creatine kinase [total], creatine 
phosphate, and creatinine); and muscle regeneration (myostatin and follistatin) 
− DMD Upper Limb Patient-Reported Outcome Measures (DMD UL-PROM) 
− Pediatric Outcomes Data Collection Instrument (PODCI) 
− DMD Lifetime Mobility Scale (DMD-LMS) 
− Resource utilization including the incidence of hospitalizations for orthopedic injury 
or surgery, pulmonary infections, and antibiotic usage 
 
• Ambulatory subjects only  
− 10-Meter Walk/Run Time (10MWRT) 
− Incidence of loss of ambulation (defined by 10MWRT > 30 seconds) 
− North Star Ambulatory Assessment (NSAA) 
3 
STUDY DESIGN 
This Phase 2, multi-center, randomized, double-blind, placebo-controlled trial will assess the 
safety and efficacy of allogeneic cardiosphere-derived cells (CDCs), or CAP-1002, administered 
as four IV infusions, one every three months, for the treatment of subjects with DMD. Subjects 
with a clinical diagnosis of DMD confirmed by genetic testing and evidence of skeletal muscle 
impairment will undergo a battery of tests and procedures during a 30-day screening period to 
determine eligibility based on protocol inclusion and exclusion criteria.  
Eligible subjects will be prospectively randomized in stratified permuted blocks to CAP-1002 or 
placebo (1:1 ratio) approximately 7 days prior to the first IV infusion of IP on Day 1. 
Randomization will be stratified by site and entry item score of the PUL 1.2. Subjects will 
undergo baseline safety and efficacy assessments (APPENDIX A) prior to the first infusion of IP 
(CAP-1002 or placebo). Administration of IP (Day 1) should occur within a maximum of 14 
days following randomization; if a delay of more than 14 days between randomization and IP 
administration is unavoidable, a conversation between the Investigator and Medical Monitor 


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should occur to determine the need for repeat assessments prior to infusion. Subjects that are not 
randomized may be re-screened at the discretion of the Investigator. 
Subjects will complete study assessments at Screening; Baseline (≤ 2 days prior to Day 1); Day 
1; Week 4 (±7 days); and Months 3, 6, 9, and 12 (±14 days, each). If the subject can travel to the 
investigative site, blood samples will be collected at Week 6 (±7 days) and Month 4.5 (±14 
days). 
All IV infusions will be conducted in an outpatient setting at the investigative site on Day 1 and 
Months 3, 6, and 9. Prior to each IP infusion, medication(s) will be administered to the subject as 
determined by the Investigator based on the pre-treatment guidelines and/or institutional 
protocols to minimize the risk of potential severe allergic reactions such as anaphylaxis. Subjects 
will be observed in the outpatient setting for at least two hours post infusion and then discharged 
the same day if medically cleared by the site Investigator. 
As part of these visits, subjects will complete a safety phone call 14 days (±3 days) after each IP 
infusion, and if clinically indicated, an unscheduled in-person visit will be performed at the 
investigative site with targeted assessments based on presentation of signs and symptoms. 
Blood samples for DSA testing will be collected at Baseline, Week 4, 14-30 days prior to the IP 
infusions scheduled for the Month 3, 6 and 9 visits, and Month 12. Blood collections for clinical 
laboratory and DSA testing at Week 4 and pre-dose DSA testing at Months 3, 6, and 9 will occur 
either at the investigative site or remotely at a designated central laboratory patient service 
center. Blood collection for biomarker and exploratory biomarker testing at Week 6 and Month 
4.5 will be conducted for those subjects who are able to travel to the investigative site. 
A schematic of the study design is displayed in Figure 1. 
If trial evidence suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the 
recommendation of the Data Safety Monitoring Board (DSMB), will introduce an open-label 
extension study to offer CAP-1002 to subjects who were randomized to placebo and completed 
the 12-month follow-up period of the original trial.  
Figure 1 Trial Design 
  
3.1 Sample Size and Randomization 
This trial will be limited to a total of 20 randomized subjects. 


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This is a double-blind, placebo-controlled trial. Subjects who meet all enrollment criteria will be 
prospectively randomized in stratified permuted blocks to CAP-1002 or placebo (1:1 ratio) via 
an interactive web-based response system (IWRS) accessed directly by site personnel who have 
been delegated this responsibility by the Principal Investigator (PI). Randomization will be 
stratified by site and entry item score of the PUL 1.2 at Screening (Stratum I: Score of 2 or 3; 
Stratum II: Score of 4 or 5). Subjects will be randomized approximately 7 days in advance of 
their first IP infusion (Day 1). The central randomization will be generated in SAS or comparable 
software using permuted random block sizes held in confidence by the statistician preparing the 
master randomization list. 
3.2 Data Safety Monitoring Board 
The DSMB will act in a senior advisory capacity to Capricor regarding data and safety matters 
throughout the duration of the trial. The objectives, roles and responsibilities of the DSMB, as 
well as the format and frequency of their meetings, are documented in the DSMB charter. 
3.3 Interim Analyses 
3.3.1 Interim Analysis 
The interim analysis was performed
 
 
 
  
 
The objective of the interim analysis was to evaluate demographic data for the Intent-to-Treat 
(ITT) Population, study drug exposure data for the Safety Population, efficacy data for the ITT 
Population, Modified Intent-to-Treat (mITT) Population and Per Protocol (PP) Population, and 
safety and adverse event data for the Safety Population. A summary of all listings and tables that 
were generated to support the analysis of the interim data are outlined in Section 9.2 
(APPENDIX B). 
The results of the interim analysis were reviewed by the DSMB. Following the interim analysis, 
enrollment in the trial was discontinued (Protocol Amendment 5 dated September 27, 2019). 
Subsequently, three additional interim analyses with updated datasets were performed and are 
described below. 
3.3.2 Interim Plus Analysis 
The interim plus analysis was performed
. The objective of the interim 
plus analysis was to further evaluate unblinded efficacy data for the ITT and PP populations. A 
summary of all listings and tables that were generated are outlined in Section 9.3 (APPENDIX 
C). 
3.3.3 Interim Plus 2 Analysis 
The interim plus analysis was performed on 
 The objective of the interim plus 
2 analysis was to further evaluate unblinded efficacy for the ITT and PP populations and 


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unblinded adverse event data for the Safety Population. A summary of all listings and tables that 
were generated are outlined in Section 9.4 (APPENDIX D). 
3.3.4 Interim Plus 3 Analysis 
The interim plus analysis was performed on 
. The objective of the interim plus 3 
analysis was to further evaluate unblinded efficacy data for the ITT Population and unblinded 
adverse event data for the Safety Population. A summary of all listings and tables that were 
generated are outlined in Section 9.5 (APPENDIX E). 
4 
GENERAL STRATEGIES FOR DATA PRESENTATION 
Data with qualifiers (e.g., “<”) will be listed with the qualifier but summarized without the 
qualifier. Subject data listings will include data collected for all subjects. Listings will be sorted 
by treatment, site, subject number, nominal visit, date and time (as applicable), unless otherwise 
indicated. 
Categorical analyses will be summarized using counts and percentages. Percentages will be 
based on the number of subjects in the analysis set for whom there are non-missing data, unless 
otherwise specified. Continuous variables, including change from baseline, will be summarized 
using descriptive statistics [n, mean, standard deviation (SD), median, minimum, maximum]. 
All statistical comparisons will be performed using two-sided tests at α=0.05 significance level, 
unless specifically stated otherwise. P-values will be presented to four decimal places. P-values 
<0.0001 will be presented as “< 0.0001.”  
All analyses will be performed using SAS v 9.3 or higher (SAS Institute, Inc, Cary, North 
Carolina, USA).  Validation and quality control of the tables, listings and figures (TLFs) will 
follow the appropriate
 standard operating procedures (SOPs). 
4.1 Treatment Groups 
The treatment groups to be presented will be those who receive CAP-1002, those who receive 
placebo, and all subjects (as applicable). 
4.2 Study Day 
The day of first IP administration is defined as Day 1. All other study days will be labeled 
relative to Day 1. Thus, study day for a particular event date on or after Day 1 is calculated as: 
(Date of event – Date of first IP administration + 1). An event that occurs prior to Day 1 is 
calculated as: (Date of event – Date of IP administration). 
The duration of an event will be calculated as (Event end date – Event start date + 1). Day 0 will 
not be used. 
The baseline value for each subject is the last non-missing value obtained prior to the time of the 
first IP administration on Day 1. 


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4.3 Handling of Dropouts or Missing Data 
Subject-level listings will present data as reported. Missing or partially missing dates that are 
required for date-dependent definitions (e.g., treatment-emergent adverse events (TEAEs), 
concomitant medications) will be assumed to be the most conservative date possible. 
For the primary efficacy endpoint, no imputation will be performed and the mixed-model 
repeated measures (MMRM) analysis will use all available data to estimate the mean treatment 
effect. 
An AE with a completely missing start date will be considered treatment-emergent; similarly, an 
AE that started the same month and year as IP administration but with missing start day will be 
considered treatment-emergent.  
AEs with missing seriousness will be counted as “serious” in tables and missing in listings; 
likewise, AEs with missing severity will be counted as “severe” in tables and missing in listings, 
and AEs with missing relatedness to the IP and/or IP administration procedure will be counted as 
“possible” and missing in listings.  
Medical history with missing stop dates will be considered ongoing. Medications with missing 
stop dates will be considered in concurrent use during the study and counted in the summary 
table of concomitant medications unless the start date is after the last IP administration. 
4.4 Multiplicity 
No multiplicity adjustments will be made to any alpha levels used for statistical testing 
for efficacy endpoints.  P-values < 0.05 at the interim analysis were used as an indication 
of treatment effect for all efficacy endpoints.  P-values for all subsequent analyses 
performed are considered nominal, without conclusions drawn about statistical 
significance levels. 
4.5 Analysis Populations 
The following analysis populations will be defined.  
Safety Population: The Safety population will be defined as all subjects who 
receive IP. Safety endpoints for subjects will be summarized and analyzed 
according to the treatment actually received. All safety analyses will be based 
on the Safety population. 
Intent-to-Treat (ITT) Population: The ITT population will be defined as all 
subjects who are randomized. Subjects will be summarized and analyzed in the 
treatment group to which they are randomized. The analysis of the primary and 
secondary efficacy endpoints (mid-level PUL 1.2) will be based on the ITT 
population. 
Modified Intent-to-Treat (mITT) Population: For each efficacy parameter, the 
mITT population included subjects in the ITT population who had at least a 
baseline observation (i.e., mITT populations are parameter-specific). Subjects 
were summarized and analyzed in the treatment group to which they were 
randomized. At the interim analysis, the primary and secondary efficacy (mid-
level PUL 1.2) parameter analyses were repeated using the mITT population as 


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a supportive analysis. It was found that the mITT Population is equivalent to 
the ITT Population, so the mITT population was not considered for subsequent 
analyses and will not be considered for the final analysis. 
Per Protocol (PP) Population: The PP population will include subjects who 
receive IP with no protocol deviations/violations that could significantly 
impact the completeness, accuracy and/or reliability of the trial data. The list 
of subjects in the per protocol population will be compiled prior to database 
lock. The primary, secondary and exploratory efficacy endpoint analyses will 
be evaluated using the PP population.  
A summary of the number and percentage of subjects in each analysis population will be 
provided. For the mITT population, the number and percentage will be based on the 
primary efficacy endpoint. A listing of subject assignment into each analysis population 
will also be displayed. 
5 
STUDY POPULATION PARAMETERS 
The study population parameters to be listed and summarized are described below. The ITT 
population will be used for the listings and summaries. Some of the summaries may also be done 
for other analysis populations defined in Section 4.5. All summaries will be presented by 
treatment group. 
5.1 Eligibility and Informed Consent 
Eligibility and informed consent parameters will be listed and will include date of informed 
consent/assent, consent to the collection and storage of exploratory biomarkers, participation in 
HOPE-1 protocol, protocol version, inclusion and/or exclusion criteria that were not met, if 
applicable, randomization date, and PUL 1.2 entry item score at randomization. 
The number of subjects meeting all screening eligibility criteria and reasons for screen failure 
will be summarized. 
5.2 Protocol Deviations 
Protocol deviations will be listed and may include, but are not limited to: 
• Visit not done or out-of-window 
• Assessment not completed or out-of-window 
• Inclusion/Exclusion 
• Informed Consent/Assent 
• IP Administration 
The number and percentage of subjects with a protocol deviation will be summarized by protocol 
deviation category.  


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5.3 Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be listed and summarized. Demographic 
characteristics consist of age, sex, ethnicity, and race. A subject’s age in years is calculated using 
the date of the informed consent/assent and date of birth using the following formula: 
 
Age = [(Informed Consent/Assent Date – Birth Date + 1)/365.25]. 
Based on age, patients will be categorized as either pediatric (age <= 16) or adult (age > 16).  
Baseline characteristics to be summarized include ulna length, height, weight, body mass index 
(BMI), screening PUL 1.2 entry item score, screening PUL 1.2 entry item score binary 
stratification (2, 3 vs. 4, 5) and dystrophin mutation type. In addition, subjects using a wheelchair 
or scooter for part-time and for full-time will be summarized. Subject height is either measured 
(i.e., standing height) or calculated from the subject’s ulna length. 
5.4 Medical Status Questionnaire 
Subject medical status will be displayed in subject listings, which will include date of 
completion, frequency of walker and manual/power wheelchair or scooter use, ventilatory 
support, supplemental oxygen use, and frequency of falls in the last 30 days. 
5.5 General Medical History 
General medical history will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA) version 21.0.  Medical history will be listed and summarized. The summary will be 
presented by MedDRA System Organ Class (SOC) and Preferred Term (PT). At each level of 
subject summarization, a subject will be counted only once if that subject experienced the event 
more than once. 
5.6 DMD Medical History 
The following DMD medical history will be listed and summarized:  
• Age at diagnosis (years), 
• Age at first chronic glucocorticoid (years), 
• Loss of stair climb and age at loss of stair climb (years), 
• Loss of stair descend and age at loss of stair descend (years), 
• Use of a walker and age at first walker use (years), 
• Part-time use of a manual/power wheelchair or scooter and age at first part-time use of a 
manual/power wheelchair or scooter (years), 
• Transition to full-time use of a manual/power wheelchair or scooter and age at first 
full-time use of a manual/power wheelchair or scooter (years), 
• Start of non-invasive ventilatory support and age non-invasive ventilatory support started 
(years), 


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• Use of a mechanical cough assist device and age at first mechanical cough assist device 
use (years), 
• History of spine surgery, 
• History of symptomatic heart failure and age at first symptoms of heart failure (years), 
and 
• History of medical (non-surgical) hospitalizations. 
The following genetic testing results included in the DMD medical history will be listed: 
• Date genetic testing sample collected 
• Name of testing lab (if Clinical Laboratory Improvement Amendments (CLIA) certified) 
• Mutation type 
• Exon 
5.7 Donor-Specific Antibodies 
Donor, donor profiles, allele, HLA, HLA Class and MFI will be listed by subject and visit. 
Subject HLA profiles will be provided in a separate listing. 
DSA data will be analyzed in the context of immune sensitization syndrome should there be an 
occurrence. 
5.8 Physical Examination 
All physical examination results will be listed. A shift table will be presented by body system for 
physical examination findings. 
5.9 Prior and Concomitant Medications 
Prescription, over-the-counter, and alternative medication use will be coded to drug class, 
preferred drug name, and generic/trade drug name using the World Health Organization Drug 
Global dictionary (WHODrug Global) version September 1, 2017. Medications that were 
stopped before the start of the IP administration procedure will be considered “pre-treatment.” 
All other medications will be considered “concomitant.” Medications that were started or 
ongoing at the time the IP administration procedure was started will be considered “baseline” (a 
subset of “concomitant”). Pre-treatment, baseline, and concomitant medications will be listed 
separately.  
Frequencies and percentages of subjects reporting or receiving cardiac and steroid medications 
will be summarized by WHODrug Global Anatomic Therapeutic Chemical (ATC) Level 2 and 
Preferred Term. Pre-treatment and baseline cardiac and steroid medications will be summarized 
separately from concomitant cardiac and steroid medications.  
At each level of subject summarization, subjects who reported one or more medication within 
that level are only counted once for that level. 


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5.10 Planned Medical/Surgical Procedures 
All reported elective medical and/or surgical procedures (e.g., wisdom tooth extraction) that 
were not the result of an adverse event will be displayed in subject listings. For each procedure, 
the type of procedure, indication, and start/end date will be reported. 
Any administered medication(s) related to the planned medical/surgical procedure(s) will be 
captured as a concomitant medication. 
5.11 IP Administration 
Details of IP administration will be listed. The number of subjects that completed IP infusion at 
each visit will be summarized. This is defined as subjects that completed (without interruption or 
syringe pump interrupted and restarted) both IP syringe administrations. For each visit, the total 
dose delivered (M cells) from both the first and second IP syringe administration, the number of 
patients who completed each IP syringe administration, reasons IP syringe was not completed, 
duration of IP administration (minutes), and total dose of IP syringe delivered (M cells) will be 
summarized. In addition, for the second IP syringe, the reasons the second IP syringe was not 
administered will also be summarized. 
5.12 Subject Study Progress 
A listing of subject study progress will show dates of per protocol study visits and unscheduled 
visits. The number of subjects who completed each visit will be summarized. 
5.13 Subject Disposition 
All screen failures will be listed along with the primary reason for screen failure. 
Subject disposition will be summarized by treatment group for the ITT population overall, by 
site, and by the binary stratification of entry item score of PUL 1.2 at screening. The number of 
subjects who completed the study, the number of subjects who discontinued from the study, and 
the primary reason for discontinuation will be summarized. 
6 
EFFICACY ANALYSES 
Listings and summaries of the efficacy parameters will be done for the ITT population, unless 
indicated otherwise. All summaries will be presented by treatment group. Efficacy parameters 
are described below. 
6.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is change from baseline to Month 12 in the mid-level (elbow) 
dimension of the PUL 1.2. The hypothesis set to be tested is: 
Ho: μc - μp = 0 
Ha: μc - μp ≠ 0 
where μc and μp are population mean absolute changes from baseline in CAP-1002- and placebo-
treated patients, respectively. 


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A MMRM analysis will be used to analyze the primary efficacy endpoint using the ITT 
population. The results for Month 3, 6, 9 and 12 visits will be modeled with visit, treatment, and 
treatment-by-visit interaction as the main effects; baseline measurement, site and binary 
stratification of entry item score of the PUL 1.2 at screening (2, 3 vs. 4, 5) will be included as 
covariates in the model. An autoregressive (AR(1)) covariance structure will be the covariance 
structure to model within-subject errors. The Kenward-Roger’s (K-R) approximation will be 
used to estimate the denominator degrees of freedom. The primary comparison will be the 
contrast between CAP-1002 and placebo at Month 12.  
As a supportive analysis, the analysis may be evaluated in the PP population. 
6.2 Secondary Efficacy Endpoints 
Supportive secondary efficacy endpoints will be change from baseline in: 
• Mid-level (elbow) dimension of the PUL 1.2 at Months 3, 6, and 9; 
• Regional systolic LV wall thickening at Months 6 and 12. 
For both secondary efficacy endpoints, the same model described in Section 6.1 will be used. For 
the mid-level (elbow) PUL 1.2 analysis, the comparisons of interest will be the contrasts between 
CAP-1002 and placebo at Months 3, 6, and 9. For the regional systolic LV wall thickening 
analysis, the comparisons of interest will be the contrasts between CAP-1002 and placebo at 
Months 6 and 12.  
As supportive analyses, these analyses may be evaluated in the PP population. 
6.3 Exploratory Efficacy Endpoints 
For an exploratory analysis, the mean change from baseline for the endpoints defined below will 
be analyzed using the same model described in Section 6.1. 
As supportive analyses, these analyses may be evaluated in the PP population. 
6.3.1 PUL Scale 
All subjects, regardless of ambulatory status, will complete testing in both the 1.2 and 2.0 
modules in the same preferred arm. All observed values will be listed. Observed totals and 
changes from baseline for each dimension [high-level (shoulder), mid-level (elbow), distal-level 
(wrist and hand)] will also be listed. 
Using the model defined in Section 6.1, the comparisons of interest will be the contrasts between 
CAP-1002 and placebo for change from baseline in the following: 
• Combined mid-level (elbow) and distal-level (hand and wrist) dimensions of the PUL 
1.2 at Months 3, 6, 9, and 12; 
• Combined high-level (shoulder), mid-level (elbow) and distal-level (hand and wrist) 
dimensions of the PUL 1.2 at Months 3, 6, 9, and 12; 
• Mid-level (elbow) dimension of the PUL 2.0 at Months 3, 6, 9, and 12; 
• Combined mid-level (elbow) and distal-level (hand and wrist) dimensions of the PUL 
2.0 at Months 3, 6, 9, and 12; 


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• Combined high-level (shoulder), mid-level (elbow) and distal-level (hand and wrist) 
dimensions of the PUL 2.0 at Months 3, 6, 9, and 12. 
6.3.2 Strength Testing 
All subjects, regardless of ambulatory status, will complete grip, pinch (tip and key), and elbow 
flexion strength testing on the same side throughout the duration of the trial. Absolute values will 
be measured and their corresponding changes from baseline will be listed and summarized. 
Using the model defined in Section 6.1, the comparisons of interest will be the contrasts between 
CAP-1002 and placebo for change from baseline in the following: 
• Grip strength at Months 3, 6, 9, and 12; 
• Tip-to-tip pinch strength at Months 3, 6, 9, and 12; 
• Key pinch strength at Months 3, 6, 9, and 12; 
• Elbow flexion strength at Months 3, 6, 9, and 12. 
6.3.3 DMD Upper Limb PROM 
The subject or parent/caretaker will evaluate the perceived difficulty in performing the activities 
of daily living classified into four domains including Food/Nutrition, Self Care, 
Household/Environment, and Leisure and Communication. Observed values and changes from 
baseline, overall and for each domain separately, will be listed and summarized. 
Using the model defined in Section 6.1, the comparisons of interest will be the contrasts between 
CAP-1002 and placebo at Months 3, 6, 9, and 12 for change from baseline in each domain and 
overall total score. 
6.3.4 Pediatric Outcomes Data Collection Instrument 
Subjects and parent/caretaker will complete the PODCI questionnaires independently of one 
another. Observed values for each of the 6 scales (Upper Extremity and Physical Function, 
Transfer and Basic Mobility, Sports and Physical Functioning, Pain/Comfort, Happiness and 
Global Function) will be listed. 
6.3.5 DMD Lifetime Mobility Scale 
The subject and parents/caretakers will complete the DMD-LMS questionnaires independently of 
one another. Observed values for each of the 3 sub-domains (Walking and Moving, Changing 
and Maintaining Body Positions, Moving and Handling Objects) will be listed separately for 
subject-reported and parent/caretaker-reported values. 
Using the model defined in Section 6.1, the comparisons of interest will be the contrasts between 
CAP-1002 and placebo at Months 3, 6, 9, and 12. The variable of interest is the change from 
baseline in the total score of a domain, calculated by summing selected items from the respective 
domain: 
• Changing and Maintaining Body Positions Domain – Items 1, 2, 3, 6, 7, 8, 10, 13, 16, 17, 
20, 22, 23, 24, 27 


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• Moving and Handling Objects Domain – Items 1, 2, 3, 4, 5, 7, 10, 11, 12, 13, 14, 15, 16, 
17, 18, 19, 20, 22, 25, 28, 29, 31, 33, 36, 39, 42, 45, 47 
6.3.6 North Star Ambulatory Assessment and 10-Meter Walk/Run Time 
Ambulatory subjects will complete the NSAA and 10MWRT. All observed values will be listed.  
6.3.7 Pulmonary Function Testing 
Pulmonary function tests (PFTs) will measure SVC, FVC, FEV1, PEF, MIP, MEP, PCF, and 
IFR. All observed values will be displayed in subject listings. 
Observed absolute values and changes from baseline will be summarized for FVC, PEF, and 
IFR. Percent predicted and changes from baseline will be summarized for FVC and PEF. 
Using the model defined in Section 6.1, the comparisons of interest will be the contrasts between 
CAP-1002 and placebo at Months 3, 6, 9, and 12 for change from baseline in the following 
parameters: 
• FVC, absolute value and percent predicted 
• PEF, absolute value and percent predicted 
• IFR, absolute value 
6.3.8 Cardiac MRI 
LV structure and function as assessed by cardiac MRI include the following parameters: 
• LV (myocardium) mass 
• LV end-systolic volume 
• LV end-systolic volume index 
• LV end-diastolic volume 
• LV end-diastolic volume index 
• LV stroke volume 
• LV ejection fraction 
• systolic wall thickening (anterior LV, lateral LV, inferior LV, septal LV) 
• regional wall motion [dyssynchrony index, circumferential uniformity ratio estimate 
(CURE)] 
• circumferential strain (global, anterior LV, lateral LV, inferior LV, septal LV) 
• LV wall thickness 
o end-systolic wall thickness average (anterior, lateral, inferior, septal) 
o end-diastolic wall thickness average (anterior, lateral, inferior, septal) 
In additional, the LV mass index (g/m2) will be calculated as 
 
LV Mass Index (g/m2) = LV Mass (g)/BSA (m2) 
where Body Surface Area (BSA) = 0.007184 * Height (cm)0.725 * Weight (kg)0.425. Height and 
weight measurements closest to the MRI scan will be used. The standing height will be used, if 
provided; otherwise, the height from ulna length will be used. 


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All observed values will be displayed in subject listings. Observed values and changes from 
baseline will be summarized for all parameters except LV wall thickness.  
Using the model defined in Section 6.1, the comparisons of interest will be the contrasts between 
CAP-1002 and placebo at Months 6 and 12 for change from baseline in all parameters except LV 
wall thickness. 
6.3.9 Biomarkers 
All observed values will be listed for biomarkers, which may include osteopontin, IL-1ß, IL-2, 
IL-6, IL-10, TNF-α, CXCL10, troponin I (cardiac, fast skeletal, slow skeletal), troponin T, CK-
MM, CK-MB, creatine kinase (total), creatine phosphate, creatinine, myostatin, and follistatin. 
6.3.10 Resource Utilization 
No endpoint-specific displays will be produced. 
7 
SAFETY ANALYSES 
Listings and summaries of the safety parameters will be done for the Safety population. All 
summaries will be presented by treatment group. Safety parameters are described below. 
7.1 Adverse Events 
AEs will be coded using MedDRA coding system (Version 21.0). Potential primary safety 
endpoints, described in Section 2.2.1, will be adjudicated by an independent Clinical Events 
Committee (CEC). 
The following AEs are defined as treatment-emergent AEs (TEAEs): 
- 
AEs occurring after the initiation of the IV catheter placement for the initial dose of IP; or 
- 
AEs with completely missing start date, or similarly, AEs that started the same month and 
year as IP administration but with missing start day. 
Subject listings of all adverse events as reported will be provided. A separate listing will be done 
for TEAEs as adjudicated by the CEC.  Serious AEs, primary safety endpoints as adjudicated, 
TEAEs adjudicated as related to IP or administration procedure, and hypersensitivity reactions as 
adjudicated will be listed separately.   
All summary tables will be reported using TEAEs as adjudicated by the CEC. A summary of the 
primary safety endpoints will be presented. In addition, TEAEs related to IP or administration 
procedure and hypersensitivity reactions will be summarized. 
AEs will be displayed by MedDRA SOC and PT, with subjects who have the same AE counted 
only once for that event and subjects who have more than one AE within a SOC counted only 
once in that SOC. The numbers and percentages of subjects reporting an event, as well as the 
number of events that were reported, will be calculated by treatment group.  
7.1.1 Clinical Events Committee 
In order to apply some level of consistency and standardization, all potential primary safety 
endpoints will be adjudicated by a CEC. The CEC can combine AEs reported separately into a 


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single AE, can change the event description (i.e., the term used to report the AE) and can change 
the status of the reported event to a non-AE. 
Any adjudicated event, including changed event descriptions, will be MedDRA-coded. 
7.2 Partner Reported Pregnancy 
Data from the Pregnancy Report Form will be listed, if applicable. 
7.3 Laboratory Tests (Hematology, Serum Chemistry, and Urinalysis) 
Hematological testing will include complete blood count (CBC), white blood cells (WBC) 
differential (absolute and percentage), hemoglobin, hematocrit, and platelet count. 
Serum chemistry testing will include basic metabolic panel (Glucose, Sodium, Potassium, 
Chloride, Bicarbonate, Blood Urea Nitrogen (BUN), Creatinine, Calcium), comprehensive 
hepatic panel (Albumin, Alkaline Phosphatase, Total Protein, Alanine Aminotransferase (ALT), 
Aspartate Aminotransferase (AST), Gamma-Glutamyl Transferase (GGT), Direct Bilirubin, 
Total Bilirubin), and Creatine Kinase. Creatine Kinase isoenzymes (CK – Total, CK – BB, CK – 
MB, and CK – MM) will be included in displays as serum chemistry parameters. 
Urinalysis analytes that will be tested include appearance, bilirubin, color, nitrite, occult blood, 
pH, protein, specific gravity, glucose, ketones, red blood cells (RBC) and WBC. If required, 
microscopic analysis of sediment will be performed and reported per occurrence. 
For hematology, serum chemistry, and urinalysis quantitative tests, summary statistics will be 
presented for the observed values at each visit.  Summary statistics will also be presented for the 
change from baseline values to each post-baseline visit. Scheduled assessments will be 
summarized, and unscheduled events will only be listed.  
For all tests, results will be displayed in subject listings, with those values falling outside the 
laboratory reference range flagged.  Laboratory reference ranges will be provided by the 
laboratory site(s) and will be included in an appendix of the clinical study report. 
7.4 Vital Signs, Height, Weight and BMI 
Vital signs will include systolic and diastolic blood pressure, heart rate, respiratory rate, body 
temperature and pulse oximetry (SpO2). Pre-infusion observed values and changes from baseline 
will be summarized at each post-baseline visit. Scheduled assessments will be summarized, and 
unscheduled events will only be listed.  
 
Listings of vital signs, ulna length, height, weight, and BMI will be provided. Height will either 
be measured (i.e., standing height) or calculated from the subject's ulna length. 
7.5 12-Lead Electrocardiograms  
All 12-lead electrocardiogram (ECG) results will be displayed in subject listings. 


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8 
DEVIATIONS FROM STATISTICAL METHODS IN THE 
PROTOCOL 
This final version 3.0 of the statistical analysis plan (SAP) supersedes all previous versions. 
There were no changes to the conduct of the study since the last protocol amendment. Analyses 
planned but not performed and the rationales for the changes are as follows. 
The following exploratory efficacy endpoints will not be analyzed: 
• High-level (shoulder) dimension of the PUL 1.2; 
• Distal-level (wrist and hand) dimension of the PUL 1.2; 
• High-level (shoulder) dimension of the PUL 2.0; 
• Distal-level (wrist and hand) dimension of the PUL 2.0; 
• Grip strength, percent predicted, at Months 3, 6, 9, and 12; 
• Tip-to-tip pinch strength, percent predicted, at Months 3, 6, 9, and 12; 
• Key pinch strength, percent predicted, at Months 3, 6, 9, and 12; 
• Elbow flexion strength, percent predicted, at Months 3, 6, 9, and 12; 
• PODCI scales (subject and parent) at Months 3, 6, 9, and 12; 
• Parent/caretaker-reported DMD-LMS at Months 3, 6, 9, and 12; 
• NSAA at Months 3, 6, 9, and 12; 
• 10MWRT at Months 3, 6, 9, and 12; 
• Incidence of loss of ambulation (10MWRT > 30 seconds) at Months 3, 6, 9, and 12; 
• Biomarkers at Months 3, 6, 9, and 12; 
• Resource utilization, including hospitalizations for orthopedic injury or surgery and for 
pulmonary infections, over the course of the trial. 
 
Originally, it was planned to perform a supportive analysis of the primary efficacy endpoint on 
the mITT Population. However, it was discovered that the mITT Population is equivalent to the 
ITT Population, so analyses of efficacy will only be performed on the ITT and PP populations.  
Also, originally, it was planned to perform the secondary and exploratory efficacy endpoint 
analyses on the PP population only. However, it was decided that the same model will be used 
for the secondary and exploratory endpoints as in the primary efficacy endpoint, so the analyses 
will be done on the ITT Population as well for all efficacy endpoints except DMD-LMS. 
 
 






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1  
Sites will complete assessments in the following sequence: 1) QOL (DMD UL-PROM, PODCI, and DMD-LMS), 2) safety and other trial assessments, 
excluding blood and urine collections (e.g., vital signs, height, weight, 12-lead electrocardiogram [ECG], etc.), 3) pulmonary function testing (PFT),  
4) PUL 1.2 and 2.0, 5) grip strength, 6) pinch strength (key and tip-to-tip), 7) elbow flexion strength, 8) NSAA (if ambulatory), 9) blood and urine 
collections, 10) cardiac MRI (if applicable), and 11) IP Infusion (if applicable). All efforts must be made for the same clinical evaluator to complete 
assessments for the same subject at the same time of day throughout the trial (preferably in the morning). 
2  
All attempts must be made to perform the trial assessments indicated for the Month 12 visit (i.e., final comprehensive visit) for subjects that decide 
to early terminate from the trial before completion and after starting at least one IP infusion. 
3    Subjects will be randomized between approximately 7 days in advance of their first IP infusion on Day 1. This lead time is to ensure adequate IP shipping 
times (see IP Manual for shipping specifications). Randomization will be stratified by site and entry item score of the PUL 1.2 at screening. 
Administration of IP on Day 1 should occur within a maximum of 14 days following randomization; if a delay of more than 14 days between 
randomization and IP administration is unavoidable, a conversation between the Investigator and Medical Monitor should occur to determine the need for 
repeat assessments prior to infusion. Subjects that are not randomized may be re-screened at the discretion of the Investigator. 
4  
Updates regarding frequency of wheelchair use, transition to wheelchair full time, ventilatory support, and frequency of falls. 
5  
A blood sample for tryptase should be obtained within 3 hours of the onset of allergic signs or symptoms, and a second red top tube should be drawn 
within 3 hours of a severe allergic reaction, and frozen at -20°C, for other future analyses. 
6  
All IP infusions will be conducted in an outpatient setting at the investigative site. Prior to each IP infusion, medications will be administered to 
the subject as determined by the Investigator based on the pre-treatment guidelines provided by Capricor and/or institutional protocols to minimize 
the risk of potential severe allergic reactions such as anaphylaxis. Subjects will be observed for at least 2 hours post infusion, including pulse 
oximetry monitoring for at least 30 minutes post infusion. Sites will observe local institutional policies related to parenteral infusions and post-
infusion monitoring. 
7  
A safety phone call will be performed 14 days (±3 days) after each IP infusion, and if clinically indicated, an unscheduled in-person visit will be 
performed at the investigative site with targeted assessments based on presentation of signs and symptoms. 
8  
Ulna length will be measured in all subjects. Standing height will be measured if a subject is capable. If standing height cannot be measured, height 
will be calculated using a measurement of ulna length per Section 13.1.2 of the protocol. 
9  
Paired forced-maneuver testing will be performed on Screening Day 1 and Day 2 (approximately 24 hours between testing sessions) to confirm 
acceptable FVC variance (exclusion criterion 7). PFT testing sequence: SVC, forced maneuver (FEV1/FVC/PEF), MIP, MEP, PCF, and IFR. 
10  Blood collections for clinical laboratory and DSA testing at Week 4 and pre-dose DSA testing at Months 3, 6, and 9 will occur either at the 
investigative site or remotely at a designated central laboratory patient service center. 
11  Blood and urine samples will be collected using trial-specific laboratory kits, and then shipped to and tested at a central laboratory. Required sample 
collection for a visit may occur on multiple days; if the visit includes an IP infusion, sample collections should occur prior to IP administration. 
Baseline blood samples may be collected on Day 1 prior to IP administration to reduce number of venipunctures. 
12  Basic metabolic panel (Glucose, Sodium, Potassium, Chloride, Bicarbonate, BUN, Creatinine, Calcium), comprehensive hepatic panel (Albumin, 
Alkaline Phosphatase, Total Protein, ALT, AST, GGT, Direct Bilirubin, Total Bilirubin). 
13  CBC with WBC differential, hemoglobin, hematocrit and platelet count 
14  Appearance, bilirubin, color, nitrite, occult blood, pH, protein, specific gravity, glucose, ketones, RBC, and WBC. If required, microscopic analysis of 
sediment will be performed and reported per occurrence 


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15  DMD genetic testing will be available at screening for subjects who have not previously completed genetic testing or whose historical genetic 
results were not performed at a CLIA-certified laboratory as determined by an Investigator. The turn-around time for final results may exceed the 
30-day screening window; allow 29-49 days for receipt of final test results. 
16   Week 6 and Month 4.5 blood samples will only be collected at the investigative site.  
17 
Biomarkers may include those of muscle inflammation (osteopontin); systemic inflammation (IL-1ß, IL-2, IL-6, IL-10, TNF-α, CXCL10); muscle 
damage (troponin I [cardiac, fast skeletal, slow skeletal], troponin T, CK-MM, CK-MB, creatine kinase [total], creatine phosphate, and creatinine); and 
muscle regeneration (myostatin and follistatin). 
18  Collected only if separate informed consent and/or assent provided  
19  Subjects will undergo cardiac MRI if they are physically capable as determined by an Investigator. Subjects that cannot complete a cardiac MRI as part of 
the trial will complete an echocardiogram at screening using the site’s local equipment, acquisition protocol, and evaluation procedures. The reported LVEF 
from a local interpretation, whether it’s measured via cardiac MRI or echocardiogram, will be used to assess eligibility (exclusion criterion 1). 


Statistical Analysis Plan 
 
Final v. 3.0 
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CONFIDENTIAL 
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9.2 APPENDIX B: Table of Contents – Interim Analysis Tables and Listings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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9.3 APPENDIX C: Table of Contents – Interim Plus Analysis Tables and 
Listings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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9.4 APPENDIX D: Table of Contents – Interim Plus 2 Analysis Tables and 
Listings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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9.5 APPENDIX E: Table of Contents – Interim Plus 3 Analysis Tables and 
Listings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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20 March 2020 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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9.6 APPENDIX F: Table of Contents – Final Analysis Tables and Listings 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
Final v. 3.0 
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20 March 2020 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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Statistical Analysis Plan 
 
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SAP Addendum  Post Hoc Analysis HOPE-2 Study 
1. Introduction 
 
The following analyses are post-hoc. The additional efficacy analyses outlined below were 
deemed necessary to assess the robustness of inferences from the pre-specified analyses to 
violations of the normality assumptions in the pre-specified analyses that arose from the smaller-
than-planned sample size. For completeness, this Addendum reinstates multiple protocol-
specified endpoints previously removed from the final analysis via the Final SAP v3.0.  In 
addition, Adverse Event and cardiac and steroid medication summaries and listings are further 
detailed in this Addendum. 
  
2. Efficacy Analyses 
 
A parametric linear mixed effects model for repeated measures (MMRM) is the pre-specified 
analysis for all primary, secondary, and exploratory endpoints of the study. The original study 
and statistical analysis plan anticipate a total sample size of around 80 subjects. However, the 
final number of subjects enrolled in the study is 20. Because of the smaller sample size, the 
primary analysis model is less likely to be robust to departures for certain assumptions1. Beyond 
simply identifying if violations of assumptions exist, a critical aspect of model checking is to 
understand the consequences violations (if present) had on data interpretations2. 
 
Specifically, the smaller than intended sample size necessitates increased scrutiny on the 
assumption of the normality of residuals in the pre-specified primary, parametric MMRM 
analysis. Concern regarding robustness to departures from normality of the residuals supports the 
use of additional analyses to supplement the pre-specified model in the HOPE-2 trial.  
 
A common method for dealing with non-normality in a study with less than 30 subjects is to 
employ a non-parametric test1. Non-parametric models generally require fewer assumptions than 
parametric models and therefore inferences from non-parametric models are less dependent on 
assumptions1.2. However, parametric analyses generally have more power if assumptions are 
valid, which is also an important consideration when sample size is small. Data transformations 
can be used to alter the original distribution into a transformed distribution for which the 
normality assumption is more likely to be valid with small sample sizes while retaining use of a 
parametric model. Therefore, a data transformation can be used to satisfy normality assumptions 
without the loss of power inherent to non-parametric methods.   
 
Results from a non-parametric and / or data-transformed analyses can be compared to the 
corresponding results from a parametric analysis to assess the consequences of departures from 
assumed conditions. Additional sensitivity analyses can be used to assess the robustness of other 
aspects of the primary and sensitivity modeling approaches2. 
 
 
 


2.1. Assessment of Departures from Normality Assumptions and their Consequences in 
the HOPE-2 Trial 
 
The residuals from the pre-specified model of the primary analysis in the HOPE-2 trial will be 
plotted in a histogram and inspected visually. An inferential assessment for departure from 
normality will be implemented via the Shapiro-Wilk test.  
 
A data transformation approach will be implemented that retains as many aspects of the primary 
analysis as possible. This approach will model changes from baseline (and baseline values) after 
transforming (converting) them to percentile ranks. The primary model will then be fit to the 
percentile ranks. The estimates from this alternative analysis will be re-transformed back to the 
original scale to facilitate interpretation on the original scale.  
 
2.2. Details of the Data Transformed Model  
 
The primary efficacy analysis is change from baseline to Month 12 in the mid-level (elbow)  
dimension of the PUL 1.2 assessed via a parametric linear MMRM model to compare treatment 
groups in mean change from baseline to Month 12. If non-normality of the residuals is identified 
via the procedure identified in Section 2, a data transformation will be applied and then the 
primary MMRM model will be applied to the transformed data. This primary MMRM model on 
the transformed data tests the same hypotheses. 
  
Ho: µc - µp = 0  
Ha: µc - µ
  
 
where µc and µp are population mean of changes from baseline in CAP-1002- and placebo-
treated subjects, respectively, which on the transformed data is also a test of the medians because 
the mean and the median of a distribution of percentiles are the same.  
 
To implement this model, an MMRM analysis will be used to analyze the percentile ranked 
primary efficacy endpoint data using the same pre-specified ITT population. Data from the post-
baseline visits (Month 3, 6, 9 and 12) will be modelled with visit, treatment, and treatment-by-
visit interaction as the main effects, and ranked baseline score, site and binary stratification of 
entry item score of the PUL 1.2 at screening (2, 3 vs. 4, 5) as covariates. A First Order 
Autoregressive (AR(1)) covariance structure will be used to model the within-subject errors. The 
Kenward-
-R) approximation will be used to estimate the denominator degrees of 
freedom. The primary comparison will be the contrast between CAP-1002 and placebo at Month 
12.   
 
For a given outcome, this analysis will be implemented by calculating the percentile rank of each 
change-from-baseline value relative to all observed change-from-baseline values for that 
outcome (across all subjects and all post-baseline observation times).  The percentile ranked 
change-from-baseline is the dependent variable in the model.  
This modeling approach will be applied to primary, secondary, and some exploratory endpoints 
for the ITT Population only.   


In addition, for PUL and Cardiac MRI outcomes, Global Statistical Tests3 (GST) will be 
calculated as the averaged percentile ranked change-from-baseline.  
 
2.3. Sensitivity Models 
 
Several sensitivity models will be constructed to assess the robustness of the non-parametric 
model described above to other potential aspects of model misspecification. These analyses are 
described below and will only be performed for the primary endpoint in the ITT Population. 
 
2 3 1  P rmuta ion est 
Permutation tests at each analysis Visit (Month 3, 6, 9, and 12) will also be conducted as a non-
parametric test for assessing robustness of the primary MMRM result. Permutation tests will be 
conducted by randomly sampling (without replacement) all possible permutations of the 
 and 
 values of the outcome variable, where 
, 
 are the number of subjects in placebo and 
treatment, respectively, at time . The p-value is the proportion of permuted samples that have a 
test statistic larger than that of the observed data. 
 
2 .2. Study Site 
An additional issue related to the smaller than originally intended sample size is the number of 
subjects per site. Ideally, there should be at least two subjects per site per treatment at each post 
baseline visit in order to cleanly estimate the site effect and the treatment effect along with the 
uncertainty / inconsistency in those effects. If the number of observations falls below this 
threshold, the treatment and site effects become (partially) confounded and treatment effect 
estimates may be biased.  
 
In the smaller than planned HOPE-2 study, two sites have only 1 subject, and 3 sites have only 1 
subject per arm. Therefore, confounding and the resulting potential bias in the estimated 
treatment effect is a concern. Two sensitivity models will be performed to assess the effect from 
this potential confounding. Each change detailed below will be implemented in the non-
parametric model described above. 
1. Site will be pooled until there were at least 2 subjects per pooled site per treatment arm. 
This will be achieved by starting with the site(s) with the fewest subjects and pooling 
with the next largest site(s) until the criterion is achieved. 
2. Site will be removed from the model. 
 
2 3. . 
u li r R moval 
In addition to conducting the non-parametric analyses, outlier (unusual) observations that are 
driving the non-normality can be removed so that the normality assumptions of the pre-specified 
parametric model hold. After removal of the outlier subject(s) from the data, the residuals can be 
reassessed for normality both graphically and inferentially via the Shapiro-Wilk Test.  
 
Although outlier removal can be a useful sensitivity analysis, it is not usually an appropriate 
primary approach because it violates the intention-to-treat principle that is central to unbiased 
assessment and is a focus of ICH E9 statistical guidance. Removing just one subject in this small 


sample would remove 5% of the data and is therefore deemed less useful than non-parametric 
analyses, especially given that no a priori cut off for identifying outliers was pre-specified. 
 
2 3.4. Impu ation  Missing Da a 
 
The selected endpoints to be evaluated using imputation of missing data are as follows: 
 change from baseline for the mid-level (elbow) dimension of the PUL 1.2 at Months 3, 6, 
9, and 12 
 change from baseline for the combined high-level (shoulder), mid-level (elbow), and 
distal-level (hand and wrist) dimensions of the PUL 2.0 at Months 3, 6, 9, and 12 
 change from baseline for LVEF as assessed by cardiac MRI at Months 3, 6, 9, and 12 
 
The sensitivity of the analysis of the selected endpoints above to missing data will be evaluated 
in the ITT population using two different techniques to impute that missing data:  
1. Last z-score carried forward 
and 
2. Multiple imputation with 500 replicates using control-based pattern imputation for 
monotone missing data 
 
To implement the first method, z-scores will be calculated by visit using all raw observed values 
at that visit prior to carrying the last available z-score forward to any missing data points. Once 
all missing data is imputed with the last available z-score, change from baseline in raw z-score 
will be calculated and analyzed using the primary MMRM, and percentile ranked change from 
baseline in raw z-score will be calculated and analyzed using the primary MMRM. 
 
Subjects who do not have data for an intermediate visit but do have data for subsequent visits 
may reasonably follow the same trajectory as subjects in their respective arm, but subjects who 
discontinue treatment may follow the same trajectory as placebo-arm subjects. To use this 
reasoning with multiple imputation, intermediate missing data will first be imputed with random 
sampling using non-
the resulting 
missing data pattern will be monotone. The remaining missing data will then be imputed with 
random sampling from non-missing placebo arm data. Once all missing data is imputed, change 
from baseline will be calculated and analyzed using the primary MMRM, and percentile ranked 
change from baseline will be calculated and analyzed using the primary MMRM. 
 
2 3.5. Additi nal Tran forma ion  
 
The sensitivity of the analysis of change from baseline for the mid-level (elbow) dimension of 
the PUL 1.2 at Months 3, 6, 9, and 12 to data transformations will be evaluated in the ITT 
population using two additional data transformation methods on the raw baseline and change 
from baseline values:  
1. Ordinal ranking 
and 
2. Cube-root transformation 
 


Once the data is transformed using the above methods, the transformed values will be analyzed 
using the primary MMRM. 
 
2.4. Additional Parameters 
 
In addition to the protocol-specified efficacy endpoints, other meaningful parameters may be 
analyzed, such as combined PUL dimensions (e.g., combined mid-level (elbow) and distal-level 
(hand and wrist) dimension) for the ITT Population and PP Populations. 
 
2.5. Data Visualization 
 
Figures depicting model-adjusted least-squares means (LS-Means) by visit broken out by 
treatment arm will be produced for the primary, secondary, and some exploratory efficacy 
outcomes. This will apply to both raw and transformed outcome measures and their 
corresponding model estimates. 
 
A forest plot will be produced for all PUL endpoints showing the magnitude, significance, and 
errors associated with several measures at Month 12 simultaneously. This plot will also include 
the GST of all PUL outcomes at Month 12. The same forest plot will be produced for Cardiac 
MRI outcomes, including the corresponding GST. Forest plots will only be produced for 
transformed outcome measures. 
 
All figures will be produced for the ITT Population only. 
 
2.6. Protocol-Specified Endpoints Previously Removed from Analysis 
The final version 3.0 of the statistical analysis plan removed some protocol-specified exploratory 
endpoints from the final analysis. This Addendum reinstates the following exploratory efficacy 
endpoints for analysis: 
 High-level (shoulder) dimension of the PUL 1.2; 
 Distal-level (wrist and hand) dimension of the PUL 1.2; 
 High-level (shoulder) dimension of the PUL 2.0; 
 Distal-level (wrist and hand) dimension of the PUL 2.0; 
 Grip strength, percent predicted, at Months 3, 6, 9, and 12; 
 Tip-to-tip pinch strength, percent predicted, at Months 3, 6, 9, and 12; 
 Key pinch strength, percent predicted, at Months 3, 6, 9, and 12; 
 Elbow flexion strength, percent predicted, at Months 3, 6, 9, and 12; 
 Pediatric Outcomes Data Collection Instrument (PODCI) scales (subject and parent) at 
Months 3, 6, 9, and 12; 
 Parent/caretaker-reported DMD Lifetime Mobility Scale (DMD-LMS) at Months 3, 6, 9, 
and 12; 


 North Star Ambulatory Assessment (NSAA) at Months 3, 6, 9, and 12; 
 Biomarkers at Months 3, 6, 9, and 12. 
All PUL and strength endpoints above will be analyzed using summary statistics, the primary 
MMRM, and the percentile ranked model described above for the ITT and PP Populations. All 
available data listed for the ITT population. 
CK Isoenzyme biomarkers will be analyzed similarly but for the safety population, with all 
available data listed for the safety population within the serum chemistry laboratory listing. 
Other biomarkers will be analyzed only using the percentile ranked model for the ITT 
population, with all available data listed for the ITT population. 
PODCI, parent/caretaker-reported DMD-LMS, and NSAA endpoints above will be listed for the 
ITT Population. 
The following exploratory efficacy endpoints will not be reinstated: 
 10-Meter Walk/Run Time (10MWRT) at Months 3, 6, 9, and 12; 
 Incidence of loss of ambulation (10MWRT > 30 seconds) at Months 3, 6, 9, and 12; 
 Resource utilization, including hospitalizations for orthopedic injury or surgery and for 
pulmonary infections, over the course of the trial. 
 
3. Safety Analyses 
 
3.1. Adverse Events 
 
This study utilized an independent Clinical Events Committee (CEC) to adjudicate all potential 
primary safety endpoints. The CEC data review was conducted in a blinded fashion and the 
results were provided only when the adjudication process yielded a different conclusion on the 
Treatment-Emergent Adverse Events (TEAE) as compared to the original TEAE assessment 
(i.e., the raw TEAE data). Since the adjudicated AE data set only contains the subset of adverse 
events which the adjudication committee reviewed, these data will be listed separately and not 
summarized due to their sparseness. In order to provide a comprehensive assessment of all 
TEAEs, the raw TEAE data will be reported in listings and summary tables for the safety 
population.  
 
3.2. Cardiac and Steroid Medications 
 
Frequencies and percentages of subjects reported or receiving WHODrug Global cardiac 
medications at any time on or after Day 1 (date of first IP exposure) will be both summarized by 
WHODrug Global Anatomic Therapeutic Chemical (ATC) Level 2 and Preferred Term and 
listed. 
 
Frequencies and percentages of subjects reported or receiving WHODrug Global steroid 
medications at any time on or after Day 1 (date of first IP exposure) will be summarized 
separately for systemic use and non-systemic use, where steroid medications with reported 


indications as DMD, DMD treatment, or SOC for DMD are considered for systemic use, and 
steroid medications with other indications are considered for non-systemic use. Both summaries 
will be presented by WHODrug Preferred Term. All steroid medications on study, along with 
their reported indications, will be listed. 
 
4. Pharmacoeconomic Analysis 
 
An exploratory analysis was planned to explore all-cause hospitalizations, hospitalizations for 
orthopedic injury/surgery or pulmonary infections, and antibiotic usage. Billing information was 
not to be collected; rather, standardized, composite or bundled costings of national averages was 
planned to be used in the analysis. Given the small sample size and minimal observations on 
trial, this analysis was not completed. 
 
 
References 
1. 
Siegel S. Nonparametric Statistics. Am Stat 1957;11(3):13 9. 
2. 
Mallinckrodt CH. and Ilya Lipkovich.  A practical guide to analyzing longitudinal clinical 
trial data.  CRC Press.  Boca Raton.  2017 (Chapter 11). 
3. 
O'Brien PC. Procedures for comparing samples with multiple endpoints. Biometrics 1984; 
40: 1079-87. 
 
 



Prot_001.pdf: 
 
CLINICAL TRIAL PROTOCOL 
A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL 
EVALUATING THE SAFETY AND EFFICACY OF INTRAVENOUS DELIVERY OF 
ALLOGENEIC CARDIOSPHERE-DERIVED CELLS IN SUBJECTS WITH 
DUCHENNE MUSCULAR DYSTROPHY (HOPE-2) 
Protocol Number: 
CAP-1002-DMD-02 
Trial Phase: 
Phase 2 
Product Name: 
CAP-1002 Allogeneic 
Cardiosphere-Derived Cells 
IND Number: 
 
Indication: 
Duchenne Muscular Dystrophy 
Sponsor: 
Capricor, Inc. 
8840 Wilshire Blvd., 2nd Floor 
Beverly Hills, CA  90211 
Sponsor Contact: 
 
Original: 
Amendment 1.0: 
Amendment 2.0: 
Amendment 3.0: 
Amendment 4.0: 
Amendment 5.0: 
20-Oct-2017
01-Dec-2017
28-Feb-2018
09-Jul-2018
17-Jan-2019
27-Sep-2019
This document is confidential and proprietary to Capricor, Inc. and its affiliates. Acceptance of this document constitutes agreement by 
the recipient that no unpublished information contained herein will be reproduced, published, or otherwise disseminated or disclosed or 
used without the prior written approval of Capricor, Inc. and its affiliates, except that this document may be disclosed in any medium to 
appropriate clinical Investigators, Institutional Review Boards, and others directly involved in the clinical investigation that is the subject 
of this information under the condition that they keep the information strictly confidential.  


CAP-1002-DMD-02 
Allogeneic Cardiosphere-Derived Cells 
Protocol Amendment 5.0 
27-Sep-2019
Page 2 of 117 
Capricor, Inc. - Company Confidential 
INVESTIGATOR’S AGREEMENT 
Trial Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial 
Evaluating the Safety and Efficacy of Intravenous Delivery of Allogeneic 
Cardiosphere-Derived Cells in Subjects with Duchenne Muscular 
Dystrophy 
Short Title: 
Halt myOPathy progrEssion in Duchenne (HOPE-2) 
Protocol Number: 
CAP-1002-DMD-02 
Amendment 5.0: 
27-Sep-2019
I have read this clinical trial protocol and agree to conduct the trial according to the investigational 
plan.  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 






CAP-1002-DMD-02 
 
Allogeneic Cardiosphere-Derived Cells 
Protocol Amendment 5.0 
 
27-Sep-2019  
 
Page 5 of 117 
 
 
Capricor, Inc. - Company Confidential 
 
2. 
SYNOPSIS 
Name of Sponsor: Capricor, Inc.  
Name of Investigational Product: CAP-1002 Allogeneic Cardiosphere-Derived Cells 
Name of Active Ingredient: Cardiosphere-Derived Cells 
IND Number: 
 
Title of Trial: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety 
and Efficacy of Intravenous Delivery of Allogeneic Cardiosphere-Derived Cells in Subjects with 
Duchenne Muscular Dystrophy 
Trial Name: Halt myOPathy progrEssion (HOPE-2) 
Trial Centers: Up to 15 (USA) 
National Principal Investigator: 
  
Principal Investigators: This is a multi-center trial with multiple Principal Investigators. 
Study Period: Approximately 24 months 
Phase of Development: 2 
Objectives:  
Primary: Evaluate the safety and efficacy of intravenous (IV) CAP-1002 administered every three 
months in subjects with Duchenne muscular dystrophy (DMD) and impaired skeletal muscle function   
Secondary: Evaluate the impact of repeated IV administrations of CAP-1002 on exploratory efficacy 
assessments of skeletal and cardiac muscle function, and quality of life 
Methodology: This Phase 2, multi-center, randomized, double-blind, placebo-controlled trial will assess 
the safety and efficacy of allogeneic cardiosphere-derived cells (CDCs), or CAP-1002, administered as 
four IV infusions, one every three months, for the treatment of subjects with DMD. Subjects with a 
clinical diagnosis of DMD confirmed by genetic testing and evidence of skeletal muscle impairment will 
undergo a battery of tests and procedures during a 30-day screening period to determine eligibility based 
on protocol inclusion and exclusion criteria.  
Eligible subjects will be prospectively randomized in stratified permuted blocks to CAP-1002 or placebo 
(1:1 ratio). To allow sufficient time for delivery of Investigational Product (IP), subjects must be 
randomized approximately 7 days in advance of their first IV infusion of Investigational Product (IP) on 
Day 1. Randomization will be stratified by site and entry item score of the Performance of the Upper 
Limb 1.2 (PUL). Subjects will undergo baseline safety and efficacy assessments (Table 3) prior to the 
first infusion of IP (CAP-1002 or placebo). Administration of IP (Day 1) should occur within a maximum 
of 14 days following randomization; if a delay of more than 14 days between randomization and IP 
administration is unavoidable, a conversation between the Investigator and Medical Monitor should 
occur to determine the need for repeat assessments prior to infusion. Subjects who are not randomized 
may be re-screened at the discretion of the Investigator.  


CAP-1002-DMD-02 
 
Allogeneic Cardiosphere-Derived Cells 
Protocol Amendment 5.0 
 
27-Sep-2019  
 
Page 6 of 117 
 
 
Capricor, Inc. - Company Confidential 
 
Subjects will complete study assessments at Screening; Baseline (≤ 2 days prior to Day 1); Day 1; Weeks 
4 and 6 (±7 days, each); Month 3 (±14 days), Month 4.5 (±14 days), and Months 6, 9, and 12 (±14 days, 
each).  
All IV infusions will be conducted in an outpatient setting at the investigative site on Day 1 and Months 
3, 6, and 9. Prior to each IP infusion, medications will be administered to the subject as determined by 
the Investigator based on the pre-treatment guidelines provided by Capricor and/or institutional protocols 
to minimize the risk of potential severe allergic reactions such as anaphylaxis.  Subjects will be observed 
in the outpatient setting for at least two hours post infusion and then discharged the same day if medically 
cleared by the site Investigator. As part of these visits, subjects will complete a safety phone call 14 days 
(±3 days) after each IP infusion, and if clinically indicated, an unscheduled in-person visit will be 
performed at the investigative site with targeted assessments based on presentation of signs and 
symptoms. 
Blood samples for donor-specific antibody (DSA) testing will be collected at Baseline, Week 4, 14-30 
days prior to the IP infusions scheduled for the Month 3, 6 and 9 visits, and Month 12. Blood collections 
for clinical laboratory and DSA testing at Week 4and pre-dose DSA testing at Months 3, 6, and 9 will 
occur either at the investigative site or remotely at a designated central laboratory patient service center. 
Blood collection for biomarker and exploratory biomarker testing at Week 6 and Month 4.5 will be 
conducted for those subjects who are able to travel to the investigative site.  
If trial evidence suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the 
recommendation of the Data Safety Monitoring Board (DSMB), will introduce an open-label extension 
study to offer CAP-1002 to subjects who were randomized to placebo and completed the 12-month 
follow-up period of the original trial.  
The primary safety endpoints include the incidence of the following from baseline through the 12-month 
timepoint:  
• 
Acute respiratory decompensation within 2 hours following IP administration 
• 
Hypersensitivity reaction  
− 
Hypersensitivity reaction is defined as a clinical syndrome including, but not limited to, 
fever, leukocytosis, or rash with onset ≤ 2 hours post infusion and lasting < 24 hours, in 
the absence of clinical signs of concomitant infection.  
• 
All-cause mortality 
• 
Serious adverse events 
• 
Treatment-emergent adverse events related to IP or administration procedure 
• 
Immune sensitization syndrome 
− 
Immune sensitization syndrome shall be defined as: (a) clinical signs and symptoms 
consistent with systemic inflammation (e.g., fever, leukocytosis, rash, or arthralgia) with 
onset ≥ 24 hours post infusion and the absence of clinical signs of concomitant infection, 
AND (b) elevation of anti-human leukocyte antigen (HLA) antibodies against the donor 
cells (i.e., DSAs), detected ≤ 30 days following onset of syndrome, of (i) ≥ 2000 mean 
fluorescent intensity (MFI) if baseline MFI ≤ 1000, or (ii) ≥ 2 times baseline otherwise 


CAP-1002-DMD-02 
 
Allogeneic Cardiosphere-Derived Cells 
Protocol Amendment 5.0 
 
27-Sep-2019  
 
Page 7 of 117 
 
 
Capricor, Inc. - Company Confidential 
 
The primary efficacy endpoint is change from baseline to the 12-month timepoint in functional capacity 
as assessed by the mid-level (elbow) dimension of the PUL 1.2. 
The secondary safety endpoint is the incidence and severity of all adverse events through the 12-month 
timepoint.  
The secondary efficacy endpoints include the change from baseline for the following: 
• 
Mid-level (elbow) dimension of the PUL 1.2 at Months 3, 6, and 9 (Month 12 is the primary 
endpoint) 
• 
Regional systolic left ventricular (LV) wall thickening as assessed by cardiac magnetic 
resonance imaging (MRI) at Months 6 and 12  
The exploratory efficacy endpoints include the change from baseline to each assessment timepoint for 
the following assessments: 
• 
All subjects 
− 
High-level (shoulder) dimension of the PUL 1.2 
− 
High-level (shoulder) dimension of the PUL 2.0  
− 
Mid-level (elbow) dimension of the PUL 2.0 
− 
Distal-level (wrist and hand) dimension of the PUL 1.2 
− 
Distal-level (wrist and hand) dimension of the PUL 2.0 
− 
Grip strength  
− 
Key and tip-to-tip pinch strength  
− 
Elbow flexion strength 
− 
Slow vital capacity (SVC), forced expiratory volume in one second (FEV1), forced vital 
capacity (FVC), peak expiratory flow (PEF), maximum inspiratory pressure (MIP), 
maximum expiratory pressure (MEP), peak cough flow (PCF), and inspiratory flow 
reserve (IFR) 
− 
LV structure and function as assessed by cardiac MRI including ejection fraction, end-
diastolic volume, end-systolic volume, stroke volume, regional wall thickness, and 
circumferential strain 
− 
Biomarkers may include those for muscle inflammation (osteopontin); systemic 
inflammation (interleukin 1 beta [IL-1ß], IL-2, -6 and -10; tumor necrosis factor alpha 
[TNF-α] and C-X-C motif chemokine 10 [CXCL10]; muscle damage (troponin I 
[cardiac, fast skeletal, slow skeletal], troponin T, creatine kinase MM isoenzyme [CK-
MM], creatine kinase MB isoenzyme [CK-MB], creatine kinase [total], creatine 
phosphate, and creatinine); and muscle regeneration (myostatin and follistatin)  
− 
DMD Upper Limb Patient-Reported Outcome Measures (DMD UL-PROM) 
− 
Pediatric Outcomes Data Collection Instrument (PODCI) 


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− 
DMD Lifetime Mobility Scale (DMD-LMS) 
− 
Resource utilization including the incidence of hospitalizations for orthopedic injury or 
surgery, pulmonary infections, and antibiotic usage 
• 
Ambulatory subjects only  
− 
10-Meter Walk/Run Time (10MWRT)  
− 
Incidence of loss of ambulation (defined by 10MWRT > 30 seconds)  
− 
North Star Ambulatory Assessment (NSAA)  
Oversight of the trial will be provided by the blinded trial Steering Committee, an independent, unblinded 
DSMB, and an independent, blinded Clinical Events Committee (CEC) that will adjudicate all potential 
primary safety endpoints. 
Number of Subjects: Twenty (20) subjects will be randomized in the trial. 
Diagnosis and Main Criteria for Inclusion: Subjects with DMD and evidence of skeletal muscle 
impairment will be evaluated for eligibility to participate in the trial. 
Inclusion Criteria Assessed within 30 Days Prior to Randomization Unless Otherwise Noted:  
1. Male subjects at least 10 years of age at time of consent 
2. Willing and able to provide informed consent to participate in the trial if ≥ 18 years of age, and 
assent with parental or guardian informed consent if < 18 years of age 
3. Diagnosis of DMD based on clinical and phenotypic manifestations consistent with DMD (e.g., 
family history of DMD, elevated creatine kinase, dystrophin muscle biopsy, calf 
pseudohypertrophy, Gowers’ sign, and gait impairment before 7 years of age) with confirmatory 
genetic testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified 
laboratory. See exclusion criteria 4 and 5 for mutation-specific exclusions.   
4. Performance of the Upper Limb entry item score 2-5 
5. If ambulatory, 10-meter walk/run velocity < 1 meter/second 
6. Loss of independent ambulation by 18th birthday (standing unassisted or ability to take, at most, 
several steps independently is not considered ambulation)  
7. Receiving standard of care therapy at an experienced, multidisciplinary, DMD center as 
evidenced by regular cardiac and pulmonary monitoring, systemic glucocorticoid treatment, and 
at-home range of motion exercises  
8. Treatment with a systemic glucocorticoid is required for at least 12 months prior to 
randomization.  The dose must remain stable for at least 6 months prior to randomization with 
the exception of either weight-based dose adjustment or a decrease in steroid dose of ≤ 10% for 
toxicity.  For patients on chronic deflazacort, treatment with an equivalent dose of prednisone 
or prednisolone for a period of ≤ 30 days to bridge lack of availability of deflazacort during the 
6 months prior to randomization is acceptable 
9. Current and up-to-date immunizations according to children and adolescent Centers for Disease 
Control immunization schedule, unless contraindicated, including the following: meningococcal 


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and meningococcal B; tetanus, diphtheria & acellular pertussis (Tdap); and pneumococcal 
polysaccharide vaccinations 
10. Adequate venous access for parenteral IP infusions and routine blood collections in the 
judgement of the Investigator  
11. Assessed by the Investigator as willing and able to comply with the requirements of the trial 
 
Exclusion Criteria Assessed within 30 Days Prior to Randomization Unless Otherwise Indicated: 
1. Left ventricular ejection fraction (LVEF) < 35%  
2. Elbow-flexion contractures > 30° in both extremities  
3. Body mass index (BMI) > 45  
4. Documentation of exon 44 skip-amenable mutation(s) in the dystrophin gene (see Appendix 1 
for comprehensive list of mutations) 
5. Documentation of dystrophin deletion mutation(s) encompassing and limited to exons 3-7 
6. Percent predicted FVC (FVC%p) < 35% 
7. Inability to perform consistent FVC measurements within ±15% during paired testing at 
screening 
8. Risk of near-term respiratory decompensation in the judgment of the investigator, or the need 
for initiation of non-invasive ventilator support as defined by serum bicarbonate ≥ 29 mmol/L 
at screening  
9. History of non DMD-related chronic respiratory disease requiring ongoing or intermittent 
treatment including, but not limited to, asthma, bronchitis, and tuberculosis 
10. Acute respiratory illness within 30 days prior to screening 
11. Initiation of non-invasive ventilation within 30 days prior to screening, or the anticipated need 
to initiate non-invasive ventilation within the 12 months following screening 
12. Planned or anticipated thoracic or spinal surgery within the 12 months following randomization  
13. Planned or anticipated lower extremity surgery within the 12 months following randomization, 
if ambulatory 
14. Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products 
15. Initiation of treatment with metformin or insulin within 3 months prior to randomization 
16. Initiation of treatment with an FDA-approved exon skipping therapy for the treatment of DMD 
within 24 months prior to randomization or dose adjustments to the therapy within 12 months 
prior to randomization with the exception of weight-based dose adjustments 
17. Treatment with human growth hormone (HGH) within 3 months prior to randomization, unless 
on a stable dose (as determined by the site PI) for at least 24 months prior to randomization  
18. Treatment with idebenone within 3 months prior to randomization 
19. Treatment with a cell therapy product within 12 months prior to randomization 


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20. Treatment with an investigational product within 6 months prior to randomization
21. History, or current use, of drugs or alcohol that could impair their ability to comply with
participation in the trial
22. Inability to comply with the investigational plan and follow-up visit schedule for any reason, in
the judgment of the investigator
Investigational Product, Dosage and Mode of Administration: 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects assigned to CAP-1002 will receive a total dose of 150 million CDCs 
per administration.  
Duration of Treatment: CAP-1002 (150 million CDCs) or placebo is administered once every 3 
months for a total of 4 administrations. 
Duration of Trial: All subjects will be followed until 12 months post Day 1. 
Criteria for evaluation: 
Efficacy  
The following efficacy outcome measures will be performed at Months 3, 6, 9 and 12 unless otherwise 
specified: 
•
Skeletal muscle function: PUL (1.2 and 2.0), grip strength, key and tip-to-tip pinch strength,
elbow flexion strength, and, if ambulatory, NSAA
•
Pulmonary function: SVC, FVC, FEV1, PEF, MIP, MEP, PCF, and IFR




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Analysis Populations  
The following analysis populations will be defined for the trial: 
Safety Population: Subjects who begin an infusion of IP. Safety endpoints for subjects will be 
summarized and analyzed according to the treatment actually received. 
Intent-to-Treat (ITT) Population: Subjects who were randomized. Subjects will be summarized and 
analyzed in the treatment group to which they were randomized. 
Modified Intent-to-Treat (mITT) Population: For each efficacy parameter, the mITT population will 
include subjects in the ITT population who have a baseline observation (i.e., mITT populations are 
parameter-specific). Subjects will be summarized and analyzed in the treatment group to which they 
were randomized. 
Per Protocol Population: Subjects who received IP with no deviations/violations that could significantly 
impact the completeness, accuracy and/or reliability of the trial data. The list of subjects in the per 
protocol population will be compiled prior to database lock.  
Interim Analysis for Futility 
An interim analysis was performed based on data collected for the twenty treated subjects and submitted 
to the DSMB for review. The DSMB made a recommendation to continue the trial as originally designed. 
After review of the DSMB recommendation, the Sponsor decided to continue trial follow-up for the 
currently enrolled subjects but to terminate further enrollment in the trial. No additional interim analyses 
are planned.  
Safety Analysis 
Safety parameters will be evaluated using the safety population. The incidence of adverse events and 
any serious adverse events will be summarized by event types and the proportion of subjects with those 
events. There are no formal tests of hypotheses associated with the primary safety endpoint. 
Efficacy Analysis 
The primary efficacy endpoint will be evaluated in the ITT population, with possible supportive analyses 
in the mITT and PP populations. Comparisons between treatment groups on efficacy endpoints will be 
done using repeated measures linear models. Other analyses may also be done using appropriate 
parametric or non-parametric methods, depending on distributions of the data and whether or not model 
assumptions are met. An algorithm detailing the decision-making process for performing the primary 
efficacy analysis, in light of features of the data that cannot be known until the data are observed (e.g., 
outliers), will be detailed in the SAP. 
Pharmacoeconomic Analysis 
The pharmacoeconomic analysis will be done using the safety population. 


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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
SPONSOR APPROVAL .................................................................................................................3 
PROCEDURES IN CASE OF EMERGENCY ...............................................................................4 
2. 
SYNOPSIS ...................................................................................................................5 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............13 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................20 
5. 
INTRODUCTION ......................................................................................................23 
5.1. 
Background .................................................................................................................23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.4. 
Risks and Benefits ......................................................................................................28 
5.5. 
Trial Rationale ............................................................................................................29 
5.6. 
Dose Justification ........................................................................................................30 
5.6.1. 
Dosing Interval ...........................................................................................................30 
5.6.2. 
Dose Selection ............................................................................................................30 
5.6.3. 
Repeat Administrations ..............................................................................................31 
5.7. 
Trial Population ..........................................................................................................32 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................33 
6.1. 
Primary Objective .......................................................................................................33 
6.2. 
Secondary Objectives .................................................................................................33 
7. 
INVESTIGATIONAL PLAN .....................................................................................34 
7.1. 
Overall Trial Design ...................................................................................................34 
7.2. 
Trial Endpoints ...........................................................................................................35 
7.2.1. 
Primary Endpoints ......................................................................................................35 
7.2.2. 
Secondary Endpoints ..................................................................................................35 


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7.2.3. 
Exploratory Endpoints ................................................................................................35 
7.3. 
Number of Subjects ....................................................................................................36 
7.4. 
Treatment Assignment ................................................................................................37 
7.5. 
Dose Adjustment Criteria ...........................................................................................37 
7.6. 
Criteria for Trial Termination .....................................................................................37 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................42 
8.1. 
Subject Inclusion Criteria ...........................................................................................42 
8.2. 
Subject Exclusion Criteria ..........................................................................................43 
8.3. 
Screen Failures ............................................................................................................44 
8.4. 
Subject Withdrawal Criteria .......................................................................................44 
9. 
TREATMENT OF SUBJECTS ..................................................................................45 
9.1. 
Description of Investigational Product .......................................................................45 
9.2. 
Concomitant Medications ...........................................................................................45 
9.3. 
Treatment Compliance ................................................................................................45 
9.4. 
Randomization ............................................................................................................45 
9.5. 
Blinding ......................................................................................................................45 
9.6. 
Emergency Unblinding of Investigational Product ....................................................46 
10. 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT .............47 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.6. 
Discontinuation of Medications Prior to Infusion ......................................................51 
10.7. 
Administration ............................................................................................................51 
10.8. 
Post-Infusion Monitoring............................................................................................53 
10.9. 
14-Day Post-Infusion Monitoring...............................................................................53 
10.10. 
Accountability .............................................................................................................53 
10.11. 
Handling and Disposal ................................................................................................54 
11. 
ASSESSMENT OF EFFICACY ................................................................................55 


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11.1. 
Sequence of Assessments ...........................................................................................55 
11.2. 
Efficacy Assessment Training ....................................................................................55 
11.3. 
Performance of the Upper Limb .................................................................................55 
11.4. 
Pulmonary Function Testing.......................................................................................56 
11.4.1. 
Slow Vital Capacity ....................................................................................................56 
11.4.2. 
Spirometry ..................................................................................................................56 
11.4.3. 
Maximal Inspiratory & Expiratory Pressures .............................................................57 
11.4.4. 
Peak Cough Flow ........................................................................................................57 
11.4.5. 
Inspiratory Flow Reserve ............................................................................................57 
11.5. 
Strength Testing ..........................................................................................................57 
11.5.1. 
Grip Strength ..............................................................................................................58 
11.5.2. 
Pinch Strength .............................................................................................................58 
11.5.3. 
Elbow Flexion Strength ..............................................................................................58 
11.6. 
North Star Ambulatory Assessment ...........................................................................58 
11.7. 
Cardiac MRI ...............................................................................................................58 
11.8. 
Quality of Life Assessments .......................................................................................59 
11.8.1. 
DMD Upper Limb PROM ..........................................................................................59 
11.8.2. 
DMD Lifetime Mobility Scale....................................................................................59 
11.8.3. 
Pediatric Outcomes Data Collection Instrument ........................................................59 
11.9. 
Biomarkers ..................................................................................................................59 
11.10. 
Exploratory Biomarkers ..............................................................................................60 
12. 
OTHER TRIAL ASSESSMENTS .............................................................................61 
12.1. 
Demographics & Baseline Characteristics .................................................................61 
12.2. 
Medical Status Questionnaire .....................................................................................61 
12.3. 
Medical History ..........................................................................................................61 
12.4. 
Prior and Concomitant Medications ...........................................................................61 
12.5. 
Planned Medical/Surgical Procedures ........................................................................61 
12.6. 
DMD Genetic Mutation Testing .................................................................................61 
13. 
ASSESSMENT OF SAFETY .....................................................................................63 
13.1. 
Safety Parameters .......................................................................................................63 
13.1.1. 
Vital Signs ..................................................................................................................63 
13.1.2. 
Weight and Height ......................................................................................................63 
13.1.3. 
Physical Examination .................................................................................................63 


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13.1.4. 
Electrocardiogram (ECG) ...........................................................................................64 
13.1.5. 
Immunologic Assessments .........................................................................................64 
13.1.6. 
Clinical Laboratory Assessments ...............................................................................64 
13.1.6.1. 
Hematology .................................................................................................................64 
13.1.6.2. 
Serum Chemistry ........................................................................................................65 
13.1.6.3. 
Urinalysis ....................................................................................................................65 
13.2. 
Adverse and Serious Adverse Events .........................................................................65 
13.2.1. 
Definition of Adverse Events .....................................................................................65 
13.2.1.1. 
Adverse Event (AE) ....................................................................................................65 
13.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................66 
13.2.1.3. 
Expected Adverse Events ...........................................................................................66 
13.2.1.4. 
Unexpected Adverse Events .......................................................................................67 
13.2.1.5. 
Other Adverse Event (OAE) .......................................................................................67 
13.2.2. 
Relationship to Investigational Product ......................................................................67 
13.2.3. 
Recording Adverse Events .........................................................................................68 
13.2.4. 
Reporting Adverse Events ..........................................................................................69 
13.2.5. 
Pregnancy Reporting ..................................................................................................70 
13.2.6. 
Adverse Event Follow-up ...........................................................................................70 
14. 
STATISTICS ..............................................................................................................71 
14.1. 
General Considerations ...............................................................................................71 
14.2. 
Sample Size ................................................................................................................71 
14.3. 
Analysis Population ....................................................................................................71 
14.4. 
Safety Analysis ...........................................................................................................71 
14.4.1. 
Safety Endpoints .........................................................................................................71 
14.4.2. 
Adverse Events ...........................................................................................................72 
14.4.3. 
Medications .................................................................................................................72 
14.4.4. 
Clinical Laboratory Evaluations .................................................................................72 
14.4.5. 
Donor-Specific Antibodies .........................................................................................72 
14.4.6. 
Physical Examination .................................................................................................73 
14.4.7. 
12-Lead ECG, Vital Signs, and Weight......................................................................73 
14.5. 
Efficacy Analysis ........................................................................................................73 
14.5.1. 
Primary Efficacy Endpoint .........................................................................................73 
14.5.2. 
Secondary Efficacy Endpoints ....................................................................................73 


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14.5.3. 
Exploratory Efficacy Endpoints .................................................................................73 
14.6. 
Statistical Methods ......................................................................................................74 
14.6.1. 
Multiplicity .................................................................................................................74 
14.6.2. 
Missing Data ...............................................................................................................74 
14.6.3. 
Interim Analysis for Futility .......................................................................................75 
15. 
TRIAL OVERSIGHT .................................................................................................76 
15.1. 
Steering Committee ....................................................................................................76 
15.2. 
Clinical Events Committee (CEC) ..............................................................................76 
15.3. 
Data Safety Monitoring Board ....................................................................................76 
16. 
SOURCE DATA AND TRIAL DOCUMENTS ........................................................77 
16.1. 
Electronic Data Capture ..............................................................................................77 
16.2. 
Trial Monitoring .........................................................................................................77 
16.2.1. 
Source Document Requirements ................................................................................78 
16.3. 
Audits and Inspections ................................................................................................79 
16.4. 
Retention of Records ..................................................................................................79 
17. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................80 
17.1. 
Qualifications and Trainings .......................................................................................80 
17.2. 
Good Clinical Practices (GCP) ...................................................................................80 
17.3. 
HIPAA or Other Privacy Training ..............................................................................80 
17.4. 
Site Initiation ..............................................................................................................80 
17.5. 
Protocol Deviations ....................................................................................................81 
18. 
ETHICS ......................................................................................................................82 
18.1. 
Ethics Review .............................................................................................................82 
18.2. 
Ethical Conduct of the Trial .......................................................................................82 
18.3. 
Written Informed Consent and Assent .......................................................................82 
18.3.1. 
Obtaining Informed Consent and Assent ....................................................................83 
18.4. 
Subject Confidentiality ...............................................................................................83 
19. 
PUBLICATION POLICY ..........................................................................................84 
20. 
REFERENCES ...........................................................................................................85 
21. 
APPENDICES ............................................................................................................89 
21.1. 
Appendix I: Exon 44-Skip Amenable Dystrophin Mutations ....................................89 
21.2. 
Appendix II: Pre-Infusion Guidance for Minimizing Risk of Potential Severe 
Hypersensitivity Reaction ...........................................................................................90 


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21.3. 
Summary of Changes – Amendment 1.0 ....................................................................91 
21.4. 
Summary of Changes – Amendment 2.0 ....................................................................94 
21.5. 
Summary of Changes – Amendment 3.0 ....................................................................98 
21.6. 
Summary of Changes – Amendment 4.0 ..................................................................104 


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LIST OF TABLES 
 
 
Table 2: 
Abbreviations and Specialist Terms ...........................................................................20 
Table 3: 
Schedule of Assessments ............................................................................................39 
 
 
Table 5: 
Height Calculation from Ulna Length ........................................................................63 
 
 
 
LIST OF FIGURES 
Figure 1: 
Trial Design ................................................................................................................38 
 
 
 
  


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this trial protocol. 
Table 2: 
Abbreviations and Specialist Terms  
Term 
Explanation 
 
Term 
Explanation 
%p 
Percent Predicted 
 
CXCL10 
C-X-C Motif Chemokine 10 
10MWR 
10-Meter Walk/Run 
 
DCM 
Dilated Cardiomyopathy 
10MWRT 
10-Meter Walk/Run Time 
 
DMD 
Duchenne 
Muscular 
Dystrophy 
6MWT 
Six-Minute Walk Test 
 
DMD 
UL-
PROM 
DMD Upper Limb Patient-
Reported Outcome Measures 
ACEi 
angiotensin-converting 
enzyme inhibitor 
 
DMD-LMS 
DMD Lifetime Mobility Scale 
AE 
Adverse Event 
 
DMSO 
Dimethyl Sulfoxide 
ALT 
Alanine Aminotransferase 
 
DSA 
Donor-Specific Antibody 
AST 
Aspartate Aminotransferase 
 
DSMB 
Data Safety Monitoring Board 
BMI 
Body Mass Index 
 
ECG 
Electrocardiogram 
BUN 
Blood Urea Nitrogen 
 
EDC 
Electronic Data Capture 
C 
Celsius 
 
ESR 
Expedited Safety Report 
CBC 
Complete Blood Count 
 
ET 
Early Termination 
CDC 
Cardiosphere-Derived Cells 
 
FDA 
U.S. 
Food 
and 
Drug 
Administration 
CEC 
Clinical Events Committee 
 
FEV1 
Forced Expiratory Volume in 
1 Second 
CFR 
Code of Federal Regulations 
 
FVC 
Force Vital Capacity 
CK-MB 
Creatine 
kinase 
MB 
Isoenzyme 
 
GCP 
Good Clinical Practice 
CK-MM 
Creatine 
kinase 
MM 
Isoenzyme 
 
GMP 
Good Manufacturing Practice 
CLIA 
Clinical 
Laboratory 
Improvement Amendments 
 
HED 
Human Equivalent Dose 
CRF 
Case Report Form 
 
HEENT 
Head, Eyes, Ears, Nose, and 
Throat 
CRO 
Clinical 
Research 
Organization 
 
HFrEF 
Heart Failure with Reduced 
Ejection Fraction 
CT 
Computerized Tomography 
 
HGH 
Human Growth Hormone 


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Term 
Explanation 
 
Term 
Explanation 
Term 
Explanation 
 
Term 
Explanation 
HIPAA 
Health Insurance Portability 
and Accountability Act 
 
MedDRA 
Medical 
Dictionary 
for 
Regulatory Activities 
HLA 
Human Leukocyte Antigen 
 
MEP 
Mean Expiratory Pressure 
  
 
 
MFI 
Mean Fluorescence Intensity 
IB 
Investigator's Brochure 
 
MHC 
Major 
Histocompatibility 
Complex 
ICH 
International Conference of 
Harmonisation 
 
MI 
Myocardial Infarction 
IFR 
Inspiratory Flow Reserve 
 
MIP 
Mean Inspiratory Pressure 
IL 
Interleukin 
 
mITT 
Modified Intent-to-Treat 
IND 
Investigational 
New 
Drug 
Application 
 
mL 
Milliliter 
IP 
Investigational Product 
 
MOP 
Manual of Procedures 
IRB 
Institutional Review Board 
 
MRI 
Magnetic Resonance Image 
ITT 
Intent-to-Treat 
 
MSC 
Mesenchymal Stem Cells 
IV 
Intravenous 
 
NSAA 
North 
Star 
Ambulatory 
Assessment 
IWRS 
Interactive Web Response 
System 
 
OAE 
Other Adverse Events 
L 
Liter 
 
p.r.n. 
As Needed 
LDH 
Lactate Dehydrogenase 
 
PCF 
Peak Cough Flow 
LGE 
Late 
Gadolinium 
Enhancement 
 
PE 
Physical Exam 
LV 
Left 
Ventricle 
/ 
Left 
Ventricular 
 
PEF 
Peak Expiratory Flow 
LVEDV 
Left 
Ventricular 
End-
Diastolic Volume 
 
PFT 
Pulmonary Function Test 
LVEF 
Left 
Ventricular 
Ejection 
Fraction 
 
PI 
Principal Investigator 
LVESV 
Left Ventricular End-Systolic 
Volume 
 
PODCI 
Pediatric 
Outcomes 
Data 
Collection Instrument 
M 
Million 
 
PP 
Per Protocol 
MACE 
Major Adverse Cardiac Event 
 
PROM 
Patient-Reported 
Outcome 
Measure 
MCB 
Master Cell Bank 
 
PT 
Preferred Term 
 


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Term 
Explanation 
 
Term 
Explanation 
PUL 
Performance of the Upper 
Limb 
 
SVC 
Slow Vital Capacity 
QOL 
Quality of Life 
 
Tdap 
Tetanus, 
Diphtheria, 
and 
Acellular Pertussis 
RBC 
Red Blood Cell 
 
TEAE 
Treatment-Emergent Adverse 
Events 
RV 
Residual Volume 
 
TIMI 
Thrombolysis in Myocardial 
Infarction 
SAE 
Serious Adverse Event 
 
TLC 
Total Lung Capacity 
SAP 
Statistical Analysis Plan 
 
TNF-α 
Tumor Necrosis Factor Alpha 
SD 
Standard Deviation 
 
v/v 
Volume to Volume 
SOC 
System Organ Class 
 
WBC 
White Blood Cell 
SpO2 
Peripheral 
Capillary 
Hemoglobin 
Oxygen 
Saturation 
 
WHO-DD 
World Health Organization 
Drug Dictionary 
SUSAR 
Serious, 
Unexpected 
Suspected Adverse Reaction 
 
 
 
 


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5. 
INTRODUCTION 
5.1. 
Background 
Duchenne muscular dystrophy (DMD) is a severe, X-linked, progressive disease affecting 
approximately one in 3,600 to 9,200 male births (Mah et al., 2014). It is caused by mutations in 
the dystrophin gene resulting in the absence of or non-functional dystrophin protein (Hoffman et 
al., 1988). 
Dystrophin is a cytoplasmic protein encoded by the dmd gene, which links cytoskeletal actin 
filaments to membrane proteins. The dystrophin protein acts as a shock absorber during muscle 
fiber contraction by linking the actin of the contractile apparatus to the layer of connective tissue 
that surrounds each muscle fiber (Koenig et al., 1988; Fairclough et al., 2013; Aartsma-Rus et al., 
2016). 
Due to the lack of dystrophin, the connection between the actin cytoskeleton and connective tissue 
is lost, inducing excessive membrane fragility and permeability, dysregulation of calcium 
homeostasis, and oxidative damage, which results in muscle cell necrosis and a chronic 
inflammatory state. Initially, muscle necrosis is followed by regeneration, but with age, the 
regenerative ability of myofibers is lost and muscle fibers are gradually replaced by connective 
and adipose tissue. It has been postulated that chronic injury and regeneration induce satellite cell 
exhaustion. Recent studies suggest that the absence of dystrophin in satellite cells impairs their 
ability to divide properly, thus reducing the generation of myogenic progenitors that are needed 
for proper muscle regeneration (Dumont et al., 2015). As a consequence, muscle function is lost 
(Muntoni et al., 2003; Deconinck and Dan, 2007; Falzarano et al., 2015). 
DMD occurs in early childhood, with degeneration occurring progressively in the skeletal 
musculature and ultimately in the heart and respiratory muscles, resulting in premature death 
(Hendriksen et al., 2015). Progressive weakness and muscle atrophy caused by degenerating 
muscle fibers begins in the lower extremities and pelvis before spreading into the upper 
extremities. Other symptoms include loss of some reflexes, a waddling gait, frequent falls, 
difficulty when rising from a sitting or lying position or when climbing stairs, changes to overall 
posture, and impaired breathing. Many children precipitously lose the ability to run or jump. The 
atrophied muscles, in particular the calf muscles, and less commonly, muscles in the buttocks, 
shoulders, and arms, may be enlarged by an accumulation of fat and connective tissue, causing 
them to look larger and healthier than they actually are (“pseudohypertrophy”). Bone thinning and 
scoliosis are common. Ultimately, a wheelchair becomes necessary, in most cases between 12 to15 
years of age (Henricson et al., 2013).  
As the disease progresses, the muscles in the diaphragm that assist in breathing and coughing 
become weaker. Affected individuals experience breathing difficulties, respiratory infections, and 
swallowing problems. Almost all DMD patients will develop cardiomyopathy (Aartsma-Rus et al., 
2016). Pneumonia, compounded by cardiac involvement, is the most frequent cause of death, 
which typically occurs in the late teens or early 20s. However, improvements in multidisciplinary 
care, in particular respiratory care and various forms of assisted ventilation, have extended the life 
expectancy; numerous individuals with DMD now survive into their 30s, and some even into their 
40s (Emery, 2002; Bushby et al., 2010; Bushby et al., 2010). 


















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 Further information about the allergic reactions is found in the Investigator’s 
Brochure and Section 13.2.1.3.   
These collective data suggest that repeat administration of CAP-1002 should be reasonably safe in 
humans. However, the risk of severe allergic reactions should be minimized by administration of 
medications that will be determined by the Investigator based on the pre-treatment guidelines 
provided by Capricor (Section 21.2) and/or institutional protocols.   
5.7. 
Trial Population 
The target population for this trial includes pediatric and adult males with a diagnosis of DMD, 
evidence of skeletal muscle impairment regardless of ambulatory status, and on a stable regimen 
of systemic glucocorticoids (see Inclusion Criterion 8 for additional details regarding stable 
regimen of systemic glucocorticoids).   


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6. 
TRIAL OBJECTIVES AND PURPOSE 
6.1. 
Primary Objective 
The primary objective of this trial is to evaluate the safety and efficacy of intravenous CAP-1002 
administered every three months in subjects with DMD and impaired skeletal muscle function.   
6.2. 
Secondary Objectives 
The secondary objective of this trial is to evaluate the impact of repeated IV administrations of 
CAP-1002 on exploratory efficacy assessments of skeletal and cardiac muscle function, and 
quality of life.  


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Trial Design 
This Phase 2, multi-center, randomized, double-blind, placebo-controlled trial will assess the 
safety and efficacy of allogeneic CDCs, or CAP-1002, administered as four IV infusions, one every 
three months, for the treatment of subjects with DMD. Subjects with a clinical diagnosis of DMD 
confirmed by genetic testing and evidence of skeletal muscle impairment will undergo a battery of 
tests and procedures during a 30-day screening period to determine eligibility based on protocol 
inclusion and exclusion criteria.  
Eligible subjects will be prospectively randomized in stratified permuted blocks to CAP-1002 or 
placebo (1:1 ratio) approximately 7 days prior to the first IV infusion of IP on Day 1. 
Randomization will be stratified by site and entry item score of the PUL 1.2 module. Subjects will 
undergo baseline safety and efficacy assessments (Table 3) prior to the first infusion of IP (CAP-
1002 or placebo). Administration of IP (Day 1) should occur within a maximum of 14 days 
following randomization; if a delay of more than 14 days between randomization and IP 
administration is unavoidable, a conversation between the Investigator and Medical Monitor 
should occur to determine the need for repeat assessments prior to infusion. Subjects that are not 
randomized may be re-screened at the discretion of the Investigator. 
Subjects will complete study assessments at Screening; Baseline (≤ 2 days prior to Day 1); Day 1; 
Weeks 4 (±7 days); and Months 3,6, 9, and 12 (±14 days, each). If the subject can travel to the 
investigative site, blood samples will be collected at Week 6 (±7 days) and Month 4.5 (±14 days).  
All IV infusions will be conducted in an outpatient setting at the investigative site on Day 1 and 
Months 3, 6, and 9. Prior to each IP infusion, medication(s) will be administered to the subject as 
determined by the Investigator based on the pre-treatment guidelines (see Section 21.2) and/or 
institutional protocols to minimize the risk of potential severe allergic reactions such as 
anaphylaxis. Subjects will be observed in the outpatient setting for at least two hours post infusion 
and then discharged the same day if medically cleared by the site Investigator. As part of these 
visits, subjects will complete a safety phone call 14 days (±3 days) after each IP infusion, and if 
clinically indicated, an unscheduled in-person visit will be performed at the investigative site with 
targeted assessments based on presentation of signs and symptoms.  
Blood samples for DSA testing will be collected at Baseline, Week 4, 14-30 days prior to the IP 
infusions scheduled for the Month 3, 6 and 9 visits, and Month 12. Blood collections for clinical 
laboratory and DSA testing at Week 4 and pre-dose DSA testing at Months 3, 6, and 9 will occur 
either at the investigative site or remotely at a designated central laboratory patient service center. 
Blood collection for biomarker and exploratory biomarker testing at Week 6 and Month 4.5 will 
be conducted for those subjects who are able to travel to the investigative site.  
If trial evidence suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the 
recommendation of the Data Safety Monitoring Board (DSMB), may introduce an open-label 
extension study to offer CAP-1002 to subjects who were randomized to placebo and completed 
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7.2. 
Trial Endpoints 
7.2.1. 
Primary Endpoints 
The primary safety endpoints include the incidence of the following from baseline through the 12-
month timepoint:  
• Acute respiratory decompensation within 2 hours following IP administration 
• Hypersensitivity reaction  
− Hypersensitivity reaction is defined as a clinical syndrome including, but not 
limited to, fever, leukocytosis, or rash with onset ≤ 2 hours post infusion and lasting 
< 24 hours, in the absence of clinical signs of concomitant infection.  
• All-cause mortality 
• Serious adverse events 
• Treatment-emergent adverse events related to IP or administration procedure 
• Immune sensitization syndrome 
− Immune sensitization syndrome shall be defined as: (a) clinical signs and symptoms 
consistent with systemic inflammation (e.g., fever, leukocytosis, rash or arthralgia) 
with onset ≥ 24 hours post infusion and the absence of clinical signs of concomitant 
infection, AND (b) elevation of anti-human leukocyte antigen (HLA) antibodies 
against the donor cells (i.e., DSAs), detected ≤ 30 days following onset of 
syndrome, of (i) ≥ 2000 MFI if baseline MFI ≤ 1000, or (ii) ≥ 2 times baseline 
otherwise 
The primary efficacy endpoint is change from baseline to the 12-month timepoint in functional 
capacity as assessed by the mid-level (elbow) dimension of the PUL 1.2. 
7.2.2. 
Secondary Endpoints 
The secondary safety endpoint is the incidence and severity of all adverse events through the 12-
month timepoint.  
The secondary efficacy endpoints include the change from baseline for the following: 
• Mid-level (elbow) dimension of the PUL 1.2 at Months 3, 6, and 9 (Month 12 is the 
primary endpoint) 
• Regional systolic left ventricular wall thickening as assessed by cardiac MRI at Months 
6 and 12  
7.2.3. 
Exploratory Endpoints 
The exploratory efficacy endpoints include the change from baseline to each assessment timepoint 
for the following assessments: 
• All subjects 
− High-level (shoulder) dimension of the PUL 1.2 




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7.4. 
Treatment Assignment 
Subjects will be prospectively randomized in stratified permuted blocks in a 1:1 allocation to 
intravenous infusion of either CAP-1002 or placebo. See Section 9.4 for additional details related 
to randomization.   
7.5. 
Dose Adjustment Criteria 
There are no planned dose adjustments. Should an acute toxicity arise during the infusion (e.g., 
hypersensitivity reaction, pulmonary decompensation, etc.), the infusion should be terminated 
immediately, and the actual total dose administered recorded. Any decision about re-challenging 
in a subsequent infusion should be made after discussions with the Investigator, Medical Monitor, 
Data Safety Monitoring Board (DSMB), and other medical experts that may be required to make 
an informed decision. 
7.6. 
Criteria for Trial Termination 
The trial may be terminated at any time and for any reason, including, but not limited to, a 
recommendation by the DSMB for safety reasons, an action by the FDA, or decision by Capricor. 


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Figure 1: 
Trial Design 






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3 Subjects must will be randomized between approximately 7 days in advance of their first IP infusion on Day 1. This lead time is to ensure adequate IP shipping 
times (see IP Manual for shipping specifications). Randomization will be stratified by site and entry item score of the PUL1.2 at screening. Administration of 
IP on Day 1 should occur within a maximum of 14 days following randomization; if a delay of more than 14 days between randomization and IP administration 
is unavoidable, a conversation between the Investigator and Medical Monitor should occur to determine the need for repeat assessments prior to infusion. 
Subjects that are not randomized may be re-screened at the discretion of the Investigator.  
4 Updates regarding frequency of wheelchair use, transition to wheelchair full time, ventilatory support, and frequency of falls.  
5 
A blood sample for tryptase should be obtained within 3 hours of the onset of allergic signs or symptoms, and a second red top tube should be drawn within 3 
hours of a severe allergic reaction, and frozen at -20°C, for other future analyses.  
6 All IP infusions will be conducted in an outpatient setting at the investigative site. Prior to each IP infusion, medications will be administered to the subject as 
determined by the Investigator based on the pre-treatment guidelines provided by Capricor and/or institutional protocols to minimize the risk of potential severe 
allergic reactions such as anaphylaxis.  Subjects will be observed for at least 2 hours post infusion, including pulse oximetry monitoring for at least 30 minutes 
post infusion. Sites will observe local institutional policies related to parenteral infusions and post-infusion monitoring.  
7 A safety phone call will be performed 14 days (±3 days) after each IP infusion, and if clinically indicated, an unscheduled in-person visit will be performed at 
the investigative site with targeted assessments based on presentation of signs and symptoms. 
8 Ulna length will be measured in all subjects. Standing height will be measured if a subject is capable. If standing height cannot be measured, height will be 
calculated using a measurement of ulna length per Section 13.1.2.  
9 Paired forced-maneuver testing will be performed on Screening Day 1 and Day 2 (approximately 24 hours between testing sessions) to confirm acceptable FVC 
variance (exclusion criterion 7). PFT testing sequence: SVC, forced maneuver (FEV1/FVC/PEF), MIP, MEP, PCF, and IFR. 
10 Blood collections for clinical laboratory and DSA testing at Week 4 and pre-dose DSA testing at Months 3, 6, and 9 will occur either at the investigative site or 
remotely at a designated central laboratory patient service center. 
11 Blood and urine samples will be collected using trial-specific laboratory kits, and then shipped to and tested at a central laboratory. Required sample collection 
for a visit may occur on multiple days; if the visit includes an IP infusion, sample collections should occur prior to IP administration. Baseline blood samples 
may be collected on Day 1 prior to IP administration to reduce number of venipunctures.  
12 Basic metabolic panel (Glucose, Sodium, Potassium, Chloride, Bicarbonate, BUN, Creatinine, Calcium), comprehensive hepatic panel (Albumin, Alkaline 
Phosphatase, Total Protein, ALT, AST, GGT, Direct Bilirubin, Total Bilirubin). 
13 CBC with WBC differential, hemoglobin, hematocrit and platelet count 
14 Appearance, bilirubin, color, nitrite, occult blood, pH, protein, specific gravity, glucose, ketones, RBC, and WBC. If required, microscopic analysis of sediment 
will be performed and reported per occurrence 
15 DMD genetic testing will be available at screening for subjects who have not previously completed genetic testing or whose historical genetic results were not 
performed at a CLIA-certified laboratory as determined by an Investigator. The turn-around time for final results may exceed the 30-day screening window; 
allow 29-49 days for receipt of final test results. 
16 Week 6 and Month 4.5 blood samples will only be collected at the investigative site. 17 
Biomarkers 
may 
include 
those 
of 
muscle 
inflammation 
(osteopontin); systemic inflammation (IL-1ß, IL-2, IL-6, IL-10, TNF-α, CXCL10); muscle damage (troponin I [cardiac, fast skeletal, slow skeletal], troponin 
T, CK-MM, CK-MB, creatine kinase [total], creatine phosphate, and creatinine); and muscle regeneration (myostatin and follistatin). 
18 Collected only if separate informed consent and/or assent provided 
19 Subjects will undergo cardiac MRI if they are physically capable as determined by an Investigator. Subjects that cannot complete a cardiac MRI as part of the 
trial will complete an echocardiogram at screening using the site’s local equipment, acquisition protocol, and evaluation procedures. The reported LVEF from 
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8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Subjects who meet all inclusion criteria and no exclusion criteria will be eligible for randomization 
in the trial.  
8.1. 
Subject Inclusion Criteria 
Inclusion criteria will be assessed within 30 days prior to randomization unless otherwise noted:  
1. Male subjects at least 10 years of age at time of consent 
2. Willing and able to provide informed consent to participate in the trial if ≥ 18 years of age, 
and assent with parental or guardian informed consent if < 18 years of age 
3. Diagnosis of DMD based on clinical and phenotypic manifestations consistent with DMD 
(e.g., family history of DMD, elevated creatine kinase, dystrophin muscle biopsy, calf 
pseudohypertrophy, Gowers’ sign, and gait impairment before 7 years of age) with 
confirmatory genetic testing performed at a Clinical Laboratory Improvement 
Amendments (CLIA)-certified laboratory. See exclusion criteria 4 and 5 for mutation-
specific exclusions.   
4. Performance of the Upper Limb entry item score 2-5 
5. If ambulatory, 10-meter walk/run velocity < 1 meter/second  
6. Loss of independent ambulation by 18th birthday (standing unassisted or ability to take, at 
most, several steps independently is not considered ambulation) 
7. Receiving standard of care therapy at an experienced, multidisciplinary, DMD center as 
evidenced by regular cardiac and pulmonary monitoring, systemic glucocorticoid 
treatment, and at-home range of motion exercises  
8. Treatment with a systemic glucocorticoid is required for at least 12 months prior to 
randomization.  The dose must remain stable for at least 6 months prior to randomization 
with the exception of either weight-based dose adjustment or a decrease in steroid dose of 
≤ 10% for toxicity.  For patients on chronic deflazacort, treatment with an equivalent dose 
of prednisone or prednisolone for a period of ≤ 30 days to bridge lack of availability of 
deflazacort during the 6 months prior to randomization is acceptable 
9. Current and up-to-date immunizations according to children and adolescent Centers for 
Disease Control immunization schedule, unless contraindicated, including the following: 
meningococcal and meningococcal B; tetanus, diphtheria & acellular pertussis (Tdap); and 
pneumococcal polysaccharide vaccinations 
10. Adequate venous access for parenteral IP infusions and routine blood collections in the 
judgement of the Investigator  
11. Assessed by the Investigator as willing and able to comply with the requirements of the 
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8.2. 
Subject Exclusion Criteria 
Exclusion criteria will be assessed within 30 days prior to randomization unless otherwise 
indicated: 
1. Left ventricular ejection fraction (LVEF) < 35%  
2. Elbow-flexion contractures > 30° in both extremities  
3. Body mass index (BMI) > 45  
4. Documentation of exon 44 skip-amenable mutation(s) in the dystrophin gene (see Appendix 
1 for comprehensive list of mutations) 
5. Documentation of dystrophin deletion mutation(s) encompassing and limited to exons 3-7 
6. Percent predicted FVC (FVC%p) < 35% 
7. Inability to perform consistent FVC measurement within ±15% during paired testing at 
screening 
8. Risk of near-term respiratory decompensation in the judgment of the investigator, or the 
need for initiation of non-invasive ventilator support as defined by serum bicarbonate ≥ 29 
mmol/L at screening  
9. History of non DMD-related chronic respiratory disease requiring ongoing or intermittent 
treatment, including, but not limited to, asthma, bronchitis, and tuberculosis 
10. Acute respiratory illness within 30 days prior to screening 
11. Initiation of non-invasive ventilation within 30 days prior to screening, or the anticipated 
need to initiate non-invasive ventilation within the 12 months following screening 
12. Planned or anticipated thoracic or spinal surgery within the 12 months following 
randomization  
13. Planned or anticipated lower extremity surgery within the 12 months following 
randomization, if ambulatory 
14. Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products 
15. Initiation of treatment with metformin or insulin within 3 months prior to randomization 
16. Initiation of treatment with an FDA-approved exon skipping therapy for the treatment of 
DMD within 24 months prior to randomization or dose adjustments to the therapy within 
12 months prior to randomization with the exception of weight-based dose adjustments.  
17. Treatment with human growth hormone (HGH) within 3 months prior to randomization, 
unless on a stable dose (as determined by the site PI) for at least 24 months prior to 
randomization  
18. Treatment with idebenone within 3 months prior to randomization 
19. Treatment with a cell therapy product within 12 months prior to randomization 
20. Treatment with an investigational product within 6 months prior to randomization 


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21. History, or current use, of drugs or alcohol that could impair their ability to comply with 
participation in the trial 
22. Inability to comply with the investigational plan and follow-up visit schedule for any 
reason, in the judgment of the investigator 
8.3. 
Screen Failures 
Any subject who provides written informed consent/assent and is ultimately not randomized for 
whatever reason will be classified as a screen failure. All subjects, including screen failures, must 
be accounted for in the clinical database.  
Screen failures may be re-screened at the discretion of the Investigator using the originally 
assigned screening number.   
8.4. 
Subject Withdrawal Criteria 
Every effort will be made to have each randomized subject complete all elements of the trial. If a 
subject has started at least one IP infusion and withdraws prior to trial completion, all attempts 
must be made to perform the trial assessments indicated for the Month 12 visit (i.e., final 
comprehensive visit). 
Criteria for withdrawal from trial participation include the following reasons: 
• A subject may withdraw his consent at any time without prejudice to his care.  
• At the discretion of the Investigator, the subject may be withdrawn from the trial for 
lack of adherence to the investigational plan.  
• A subject may be withdrawn from the trial for an acute reaction to IP or other safety 
issue that prevents repeat infusions. In this instance, the subject should be followed on 
schedule until completion of assessments through the Month 12 visit or for at least 3 
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Site personnel and trial subjects, staff members at clinical research organizations (CROs), core 
laboratory personnel, and Clinical Event Committee (CEC) members will remain blinded to 
subject treatment assignments until follow-ups have been completed on the currently enrolled 
subjects. This is a double-blind, placebo-controlled trial. IP will be prepared for IV infusion by 
site personnel who have been appropriately delegated by the Principal Investigator. The IP 
syringes once prepared will appear identical for both treatment groups. However, an 
investigational pharmacist may be able to differentiate CAP-1002 from placebo based on the 
opacity of the thawed concentrate observed during IP preparation. For this reason, the 
investigational pharmacists will have limited interaction with the blinded investigative site 
personnel.  
Please refer to Section 9.6 for more information related to emergency unblinding of the 
investigational product.   
9.6. 
Emergency Unblinding of Investigational Product 
To maintain the overall scientific integrity of the clinical trial, further unblinding or code breaks 
should occur only in exceptional circumstances when knowledge of the actual treatment is 
absolutely essential for further management and treatment of the subject. Subject safety must 
always be the first consideration in making such a determination. Investigators are encouraged to 
discuss with the Medical Monitor prior to unblinding. In case of an emergency, the Investigator 
has the sole responsibility for determining if unblinding of a subject’s treatment assignment is 
warranted. If unblinding is deemed to be necessary, the Investigator should use the mechanism for 
emergency unblinding through the IWRS. If a subject’s treatment assignment is unblinded, 
Capricor must be notified within 24 hours after breaking the blind. The date and reason that the 
blind was broken must be recorded in the source documentation and case report form, as 
applicable. The Investigator is encouraged to maintain the blind as much as possible. Knowledge 
of the actual allocation can generally be limited and not disclosed to the subject and/or other trial 
personnel including personnel at other investigative sites, monitors, or other personnel involved in 
the trial; nor should there be any written or verbal disclosure of the code in any corresponding 
subject documents. Unblinding should not necessarily be a reason for termination from the trial. 
















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10.11. 
Handling and Disposal   
All IP materials will be disposed following each IP infusion. Site personnel will follow institutional 
policies on the proper disposal of containers and disposables coming into contact with the IP. 
Generally, disposal like other biohazard red-bag trash that is ultimately incinerated should be 
sufficient to meet local institutional policies and any other regulations or laws. 
 


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11. 
ASSESSMENT OF EFFICACY 
Assessments to evaluate efficacy will be performed at trial visits as indicated in Table 3.  
11.1. 
Sequence of Assessments 
To the best of the site’s ability, subjects should complete assessments in the following sequence 
and at the same time of day throughout the trial (preferably in the morning). Assessments must be 
completed prior to IP infusion (if applicable).  
• Quality of Life  
− DMD Upper Limb Function Patient-Reported Outcome Measures (DMD UL-
PROM)  
− Pediatric Outcomes Data Collection Instrument (PODCI) 
− DMD Lifetime Mobility Scale (DMD-LMS) 
• Safety and other trial assessments, excluding blood and urine collections (e.g., vital 
signs, height, weight, 12-lead ECG, etc.) 
• Pulmonary function testing 
• Performance of Upper Limb 1.2 and 2.0 
• Grip strength  
• Key and tip-to-tip pinch strength 
• Elbow flexion strength 
• North Star Ambulatory Assessment (ambulatory subjects only) 
• Blood and urine collections 
• Cardiac MRI 
11.2. 
Efficacy Assessment Training 
Site personnel must complete trial-specific training prior to conducting efficacy assessments for 
the trial. Standardization and consistency are essential. All efforts must be made to have the same 
clinical evaluators conduct the PFT; PUL; grip, pinch, and elbow flexion strength; and NSAA 
assessments, and the same imaging technologist conduct the cardiac MRI for a subject throughout 
the duration of the trial. The clinical evaluator performing the functional assessments with the 
subject should not administer the QOL of questionnaires to the subject. Additional details 
regarding training requirements can be found in Section 17.1 and the trial’s Manual of Procedures 
(MOP).  
11.3. 
Performance of the Upper Limb 
The Performance of the Upper Limb was designed specifically for assessing upper limb function 
in ambulant and non-ambulant DMD patients (Pane et al., 2014). All the tasks included in the PUL 
were selected to address patient prioritized activities of daily living that are typical regardless of 
age, including preschool children. The PUL includes an entry item to define the starting functional 


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testing level for a subject. The remaining PUL items are divided into three regional dimensions: 
high-level (shoulder), mid-level (elbow), and distal-level (wrist and hand). Trial subjects will 
complete testing in both the 1.2 and 2.0 modules in the same preferred arm throughout the course 
of the trial when PUL testing is required.  
Elbow contractures will be measured in each arm of a subject prior to the start of PUL testing at 
each visit that requires testing.  
PUL equipment will be standardized across investigative sites and provided by Capricor. 
Additional details regarding the PUL requirements can be found in the trial’s MOP and Clinical 
Evaluator Binder.  
11.4. 
Pulmonary Function Testing 
Pulmonary function testing (PFT) in this trial will measure slow vital capacity (SVC), forced vital 
capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), 
maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), peak cough flow 
(PCF), and inspiratory flow reserve (IFR). PFTs will be performed using equipment that meets or 
exceeds the minimal performance recommendations of the American Thoracic Society/European 
Respiratory Society and that will be provided by a centralized core lab.  
Site personnel must complete competency testing on a volunteer prior to conducting PFTs with a 
trial subject.  
Subjects will complete PFTs in the seated position prior to any other functional outcome 
measurements (i.e., PUL 1.2 & 2.0, NSAA, grip, pinch, and elbow flexion strength, and cardiac 
MRI). Every effort should be made to complete a subject’s PFTs at approximately the same time 
in the morning at each trial visit. Additional details regarding each PFT technique and requirements 
are included in the Site Manual provided by the core lab. This manual should be followed for all 
pulmonary function testing.   
11.4.1. 
Slow Vital Capacity  
SVC maneuvers will be performed prior to spirometry (forced maneuvers) because of the potential 
for muscular fatigue and volume history effects.  
Subjects will perform at least three acceptable SVC maneuvers (with no more than five total 
attempts) until the highest SVC is no more than 0.150 L greater than the next highest measurement. 
The largest acceptable SVC value will be reported.  
11.4.2. 
Spirometry 
At least three acceptable spirometry efforts (with no more than five attempts) will be obtained for 
FEV1, FVC, and PEF determinations. Acceptable forced maneuvers will have a satisfactory start 
of test and end of test (i.e., a plateau in the volume-time curve) and be free from artifacts due to 
cough, early termination, poor effort, obstructed mouthpiece, equipment malfunction, or other 
reasons. 
Quality control standards will be implemented within a testing session. The largest FEV1, FVC, 
and PEF from the 3 acceptable efforts will be reported, even if they do not come from the same 


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effort. The two largest accepted FVC values should be within ± 15% of each other. Additionally, 
the two largest accepted PEF values should be within ± 15% of each other.  
Subjects will complete paired spirometry testing at screening to confirm acceptable variance in 
FVC (exclusion criterion 7). Testing will occur on Screening Day 1 and Screening Day 2 separated 
by approximately 24 hours.  
11.4.3. 
Maximal Inspiratory & Expiratory Pressures 
Maximal inspiratory pressure (MIP) and maximal expiratory mouth pressure (MEP) are simple 
tests in which patients generate as much inspiratory or expiratory pressure as possible against a 
blocked mouthpiece. Because lung volume cannot change significantly during measurement, 
results are to a large extent independent of the properties of the lungs. They are general tests of 
neuromuscular function of the combined diaphragm, abdominal, intercostal, and accessory 
muscles (Evans and Whitelaw, 2009). 
Subjects will perform the MIP maneuvers (from residual volume (RV)) first, and the MEP 
maneuvers (from total lung capacity (TLC)) second.  
There must be at least 3 acceptable maneuvers from a maximum of five per session.  
The two largest accepted values should be within ± 15% of each other.  
Subjects will sustain maximal efforts for a total of 3-4 seconds until a plateau in pressure is 
achieved for at least 1.5 seconds.  
Site personnel must carefully judge outlier efforts, which need to be eliminated if the pressure 
reading showed no gradual increase to the plateau value, suggesting a sharp peak value. 
11.4.4. 
Peak Cough Flow 
Subjects will perform at least three cough maneuvers (with no more than five total attempts) from 
TLC for PCF determination. Site personnel must evaluate each maneuver to determine if it meets 
acceptability criteria. The largest, acceptable PCF value will be reported. 
11.4.5. 
Inspiratory Flow Reserve 
Subjects will perform at least three maximum inspiratory flow-volume maneuvers (with no more 
than five total attempts).  From stable tidal breathing, subjects will expire to RV and then inspire 
to TLC with maximum effort. Site personnel must evaluate each maneuver to determine if it meets 
acceptability criteria. The largest, acceptable inspiratory flow reserve value will be reported. 
11.5. 
Strength Testing 
Strength testing will be performed using standardized equipment that will be provided by Capricor. 
All subjects will complete grip, pinch (tip and key), elbow flexion strength testing, regardless of 
ambulatory status, on the same side throughout the duration of the trial.  Additional details 
regarding the strength testing requirements can be found in the trial’s MOP and Clinical Evaluator 
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11.5.1. 
Grip Strength 
Subjects will complete grip strength testing in the same hand throughout the course of the trial. 
Subjects will provide maximal voluntary isometric contractions for at least three seconds. A 
subject will perform contractions until the highest observed value from a valid effort is within 10% 
of the next, highest valid effort. Subjects will perform no more than five efforts. The greatest value 
from a valid effort, regardless of reproducibility, will be captured.  
11.5.2. 
Pinch Strength 
All subjects will complete “tip-to-tip” and “key” pinch strength testing, regardless of ambulatory 
status, using the same hand throughout the duration of the trial. A subject will perform pinch 
assessments for a given testing position (i.e., “tip-to-tip” or “key”) until the highest observed value 
from a valid effort is within 10% of the next, highest valid effort but, not exceeding five efforts. 
The greatest value from a valid effort for a testing position, regardless of reproducibility, will be 
captured.  
11.5.3. 
Elbow Flexion Strength 
All subjects will complete elbow flexion strength testing on the same side throughout the duration 
of the trial. A subject will perform the isometric maneuver until the highest observed value from a 
valid effort is within 10% of the next, highest valid effort up to a maximum of five efforts. The 
greatest value from a valid effort, regardless of reproducibility, will be captured.  
11.6. 
North Star Ambulatory Assessment 
The NSAA is a functional scale designed specifically for ambulatory patients with DMD. Only 
ambulatory subjects – defined as those able to complete the 10MWR without assistance – will 
complete the NSAA. The scale is composed of 17 items that range from the 10MWR to rise from 
floor. Each item will be graded on a 3-point scale. The 10MWRT will be measured and recorded 
during each testing session. Additional details regarding the NSAA testing requirements can be 
found in the trial’s MOP. 
11.7. 
Cardiac MRI 
Subjects will undergo cardiac MRI at the Screening, Month 6 and Month 12 visits (or, Early 
Termination Visit) if they are physically capable as determined by an Investigator. Subjects that 
complete the cardiac MRI will have sufficient attention span, ability to maintain a breath-hold, 
lack significant contractures that would otherwise make lying flat difficult, and fit properly within 
the MRI scanner.  
A subject’s screening cardiac MRI case will require evaluation by a site’s radiologist using 
institutional procedures. The reported LVEF from the local interpretation will be used to assess 
eligibility (exclusion criterion 1). 
It is anticipated that the duration of each MRI session will be 30-45 minutes. Acquisition 
parameters and techniques are specified in the MRI Imaging Manual. The site-based MRI 
technologists will be trained and certified in the common acquisition protocol prior to initiation of 
enrollment at each site. All trial images and applicable imaging data will be sent to and centrally 
read at an independent, central, imaging core by DMD cardiovascular MRI and imaging experts.  


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Subjects that cannot complete a cardiac MRI as part of the trial will complete an echocardiogram 
at screening using the site’s local equipment, acquisition protocol, and evaluation procedures. The 
reported LVEF from the local interpretation will be used to assess eligibility (exclusion criterion 
1).    
11.8. 
Quality of Life Assessments 
Site personnel must complete trial-specific training prior to administering the QOL questionnaires 
to a trial subject and parent/caretaker. Clinical evaluators that perform functional evaluations (e.g., 
PUL, PFTs, NSAA, and grip, pinch, and elbow flexion strength) are not to perform the QOL 
assessments. All subjects, regardless of ambulatory status, are to complete QOL assessments at 
trial visits per Table 3.  
11.8.1. 
DMD Upper Limb PROM 
The DMD Upper Limb Patient-Reported Outcome Measures (DMD UL-PROM) evaluates the 
perception of upper limb function in children and young males with DMD. The questionnaire 
consists of 32 items that cover four domains of activities of daily living: 1) food, 2) self-care, 3) 
household and environment, and 4) leisure and communication. The subject or parent/caretaker, if 
required, will evaluate the perceived difficulty in performing the activity on a three-level scale: 
cannot do, can do with difficulty, or can do easily.  
11.8.2. 
DMD Lifetime Mobility Scale 
The Duchenne Muscular Dystrophy Lifetime Mobility Scale (DMD-LMS) is comprised of three 
sub-domains: 1) walking and moving, 2) transfers and trunk stability, and 3) carrying, moving, 
and handling objects. Each subdomain is scored out of 100 points. The questionnaire, completed 
separately by both the trial subject and parent/caretaker, facilitates patient-reported outcomes of 
function that can be combined with clinically-relative milestones specific to patients with DMD.  
11.8.3. 
Pediatric Outcomes Data Collection Instrument  
The PODCI is designed to assess a subject’s overall health, pain and ability to participate in normal 
daily activities, as well as in more vigorous activities associated with young people. Eight scales 
offer a broad view of the physical, mental, and attitudinal condition for the young subject, as well 
as their treatment expectations.  
Separate subject and parent/caretaker PODCI questionnaires have been validated for pediatric 
(ages 2-11 years) and adolescent (ages 11-18 years) subjects. The subject and parent/caretaker 
must complete the questionnaires independently of one another. All prompts must be answered per 
the questionnaire’s instructions. Document all reasons for refusals and non-compliance. 
11.9. 
Biomarkers 
The following biomarkers will be collected using standardized kits and may be batch tested at a 
designated central laboratory: 
• Muscle inflammation: osteopontin  
• Systemic inflammation: IL-1β, IL-2, IL-6, IL-10, TNF-α, and CXCL10 


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• Muscle damage: troponin I (cardiac, fast skeletal, slow skeletal), troponin T, CK-MM, 
CK-MB, creatine kinase (total), creatine phosphate, and creatinine 
• Muscle regeneration: myostatin and follistatin 
The date of each collection will be captured. Reference the Laboratory Manual for additional 
details regarding the collection, processing, storage, and shipping of biomarker samples.  
11.10. 
Exploratory Biomarkers 
For subjects who provide separate consent and/or assent, blood samples for clinical research into 
exploratory biomarkers that have not been pre-identified will be collected, processed, and shipped 
to central laboratory for storage and/or analysis (including any future analysis). The date and time 
of collection will be captured. Reference the Laboratory Manual for additional details regarding 
the collection, processing, storage, and shipping of biomarker samples. 
 


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12. 
OTHER TRIAL ASSESSMENTS 
Other trial assessments will be performed as indicated in Table 3. 
12.1. 
Demographics & Baseline Characteristics 
For all subjects screened, date of birth, ethnicity, race, and dystrophin mutation type and analytical 
method will be captured. 
12.2. 
Medical Status Questionnaire 
Subjects will be evaluated for the following at screening and throughout the course of the trial:  
• Frequency of manual/power wheelchair use 
• Age permanently transitioned to a wheelchair full time  
• Ventilatory support 
• Frequency of falls 
Changes in ambulatory status (i.e., transition from ambulatory to non-ambulatory) will be 
evaluated by a subject’s performance in the 10MWR as part of the NSAA.  
12.3. 
Medical History 
Relevant and significant medical/surgical history will be collected at Screening and updated at 
Baseline.  
12.4. 
Prior and Concomitant Medications 
All medications taken within one month prior to the screening visit through trial completion will 
be captured. Medications will be reviewed at each trial visit and any medication changes, including 
new and discontinuations, will be recorded.  
For each medication, generic name, indication, dose, frequency, route, and starting and stopping 
dates/times (if applicable) will be collected. The trade name of the medication is to be reported for 
combination therapies (e.g., Alka-Seltzer, Advair, etc.). 
12.5. 
Planned Medical/Surgical Procedures 
Data associated with any elective medical and/or surgical procedure (e.g., wisdom tooth 
extraction) that is not the result of an adverse event will also be captured.   
For each procedure, the type of procedure, indication, and start date/time will be recorded. Any 
administered medication(s) related to the planned medical/surgical procedure(s) will be captured 
as a concomitant medication.  
12.6. 
DMD Genetic Mutation Testing 
DMD genetic testing will be available at screening for subjects who have not previously completed 
genetic testing or whose historical genetic results were not performed at a CLIA-certified 
laboratory as determined by an Investigator. The need for genetic testing should be assessed early 


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in the screening process, and if required, initial screening should be limited to genetic testing only 
since the turn-around time for final results may exceed the normal 30-day screening window. 
Blood samples for DMD genetic testing will be collected and analyzed at a CLIA-certified central 
laboratory. Allow 29 to 49 days for receipt of test results. 
 


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13. 
ASSESSMENT OF SAFETY 
13.1. 
Safety Parameters 
Safety assessments will be performed as indicated in Table 3. 
13.1.1. 
Vital Signs 
Heart rate, systolic and diastolic blood pressure, respiratory rate, body temperature, and blood 
oxygen saturation (SpO2) will be measured after the subject has rested for approximately 5 minutes 
and before performing ECG and spirometry testing. A single set of values will be captured. 
A subject’s SpO2 will be monitored for at least 30 minutes following each IP infusion (see 
Section 10.8). 
Vital signs will be performed using equipment provided by investigative sites that has been 
properly calibrated per institutional guidelines.  
13.1.2. 
Weight and Height 
Weight, ulna length, and standing height measurements will be performed.  
Investigative sites will make every effort to perform a weight measurement without the subject’s 
wheelchair or other assistive device (e.g., walker), if applicable.  
Ulna length will be measured in all subjects. Standing height will be measured if a subject is 
capable. If standing height cannot be measured, height will be calculated using the subject’s ulna 
length (Gauld et al., 2004). It is critical to reduce variability in ulna length and standing height 
measurements across investigative sites. Therefore, site personnel must complete trial-specific 
training prior to measuring a subject’s ulna length and standing height. 
Table 5: 
Height Calculation from Ulna Length 
Height (cm) = 
[4.605 x Ulna Length (cm)]  
+ [1.308 x Age (years)] 
+ 28.003  
Centimeter and year entries must include decimal 
places. If a subject is 18 years or older, enter “18” in 
the formula for age.  
 
13.1.3. 
Physical Examination 
The physical exam (PE) is not considered a standard of care assessment as the examiner will be 
assessing for research events. Therefore, the physical exam is to be conducted only by an 
Investigator, or designated site personnel (e.g., nurse practitioners, physician assistants, research 
fellows) listed on the Delegation of Authority Log.    
The physical examination will be a review of the major organ systems including: general 
appearance, HEENT, lymphatic, respiratory, cardiovascular, chest, abdomen, gastrointestinal, and 
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Clinically significant findings prior to investigational product administration are to be captured as 
medical history.  
Clinically significant findings after the start of investigational product administration are captured 
and reported as AEs, if they meet the definition of an AE per Section 13.2.1. 
13.1.4. 
Electrocardiogram (ECG) 
All ECG measurements will be obtained in the supine position with standardized equipment that 
meet institutional standards for clinical use. Site personnel must complete trial-specific training 
prior to ECG measurements. A 12-lead ECG measurement and rhythm strip (10 seconds) will be 
obtained after measurement of vital signs and before spirometry testing.  
The Investigator, a designated Sub-Investigator, or other appropriately trained site personnel will 
be responsible for performing 12-lead ECG assessments. The Investigator must provide his/her 
dated signature on the original paper tracing, attesting to the authenticity of the ECG machine 
interpretation, or their over-read and reinterpretation. 
ECG data will be electronically transmitted to an independent cardiologist, contracted by Capricor, 
and evaluated. The independent cardiologist, blinded to treatment assignment, will conduct an 
over-read of the ECG measurements required for the trial. Investigative sites will receive a report 
with the independent cardiologist’s ECG interpretations that must be reviewed, signed, and dated 
by an Investigator.  
13.1.5. 
Immunologic Assessments 
Serum for DSA testing and whole blood for HLA typing will be collected at each site at baseline, 
and then shipped to a central laboratory for analysis (See Laboratory Manual for shipping 
instructions).  
DSA collections at the Week 4 (±7 days) visit and 14-30 days prior to the planned date of the 
second, third, and fourth IP infusions will be assessed to determine MCB lot compatibility. These 
follow-up collections will occur either at the investigative site or remotely at a designated central 
laboratory patient service center. 
DSA samples may also be collected in the setting of clinical suspicion of immune sensitization 
syndrome in the judgment of the Investigator. See Section 7.2.1 for additional details regarding 
immune sensitization syndrome as a safety endpoint.  
13.1.6. 
Clinical Laboratory Assessments 
All blood samples are to be collected following the standard institutional procedures for blood and 
urine collection and submitted to a central laboratory for analysis.  
Instructions on collection, processing, storage and shipping the samples to the central laboratory 
are located in the Laboratory Manual. 
13.1.6.1. Hematology 
Hematological testing will include complete blood count (CBC) with white blood cell (WBC) 
differential, hemoglobin, hematocrit and platelet count 


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13.1.6.2. Serum Chemistry 
Serum chemistry testing will include: basic metabolic panel (Glucose, Sodium, Potassium, 
Chloride, Bicarbonate, BUN, Creatinine, Calcium), comprehensive hepatic panel (Albumin, 
Alkaline Phosphatase, Total Protein, ALT, AST, GGT, Direct Bilirubin, Total Bilirubin), and 
Creatine Kinase 
13.1.6.3. Urinalysis 
Analytes that will be tested include: appearance, bilirubin, color, nitrite, occult blood, pH, protein, 
specific gravity, glucose, ketones, red blood cell (RBC), and WBC. If required, microscopic 
analysis of sediment will be performed and reported per occurrence.  
13.2. 
Adverse and Serious Adverse Events 
13.2.1. 
Definition of Adverse Events 
13.2.1.1. Adverse Event (AE) 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related. It may be indicated by physical sign, symptom, clinically significant 
laboratory abnormalities, and/or disease temporally associated with a medical (investigational) 
treatment, procedure, or product, whether or not related to the medical (investigational treatment, 
procedure or product.  This definition includes intercurrent illnesses or injuries, exacerbation of 
pre-existing conditions, or events occurring due to abuse or overdose.   
Any condition that was pre-existing is not an adverse event unless there is a change in the nature, 
severity, or degree of the condition.  
Clinical laboratory abnormalities are considered AEs when deemed clinically significant by the 
Investigator and/or lead to a change in the subject’s functional status.  
An AE does not include:  
• Medical or surgical procedures (e.g., colonoscopy, biopsy). The medical condition that 
leads to the procedure is an AE. 
• Social or convenience hospital admissions where an untoward medical occurrence did 
not occur. 
• Day-to-day fluctuations of pre-existing disease or conditions present or detected at the 
start of the trial that do not worsen. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied unless more severe than expected for the subject’s 
condition. 
All Investigators conducting investigative studies supported by Capricor must report both expected 
and unexpected SAEs to Capricor, or designee, and their individual Institutional Review Board 
(IRB) in compliance with their institutional policies. Please see Section 13.2.4 or further details 
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Other risks of the infusion procedure include those risks that are possible with the intravenous 
administration. These include risks related to infection, bleeding, pain, and bruising and/or 
hematoma at the vascular access site(s).   
13.2.1.4. Unexpected Adverse Events 
An AE is considered “unexpected” if it is not listed in the Investigator’s Brochure or is not listed 
at the specificity or severity that has been observed, if the Investigator’s Brochure is not required 
or available, or if it is not consistent with the risk information described in the general 
investigational plan or elsewhere in the current application. 
“Unexpected,” as used in this definition, also refers to adverse events or suspected adverse 
reactions that are mentioned in the Investigator’s Brochure as occurring with a class of drugs or as 
anticipated from the pharmacological properties of the drug, but are not specifically mentioned as 
occurring with the particular drug under investigation. 
Expedited reporting is required for serious unexpected AEs as discussed in Section 13.2.4.   
13.2.1.5. Other Adverse Event (OAE) 
OAEs will be identified by the Medical Monitor during the evaluation of safety data for the planned 
interim analysis and Clinical Study Report.  Significant adverse events of particular clinical 
importance, other than SAEs and those AEs leading to discontinuation of the subject from the trial, 
will be classified as OAEs.   
For each OAE, a narrative may be written and included in the Clinical Study Report. 
13.2.2. 
Relationship to Investigational Product 
The Investigator will assess the relationship (causality) of an AE to the investigational product and 
administration procedure.  
Causality will be defined as follows:  
• Probable: adverse events that, after careful medical evaluation, are considered with a 
high degree of certainty to be related to the investigational product or administration 
procedure. The following characteristics will apply: 
− A reasonable temporal relationship exists between the event and the investigational 
product or administration procedure, and 
− The event is a known reaction to the investigational product or administration 
procedure, which cannot be explained by an alternative etiology commonly 
occurring in the population/individual.  
• Possible: adverse events that, after careful medical evaluation, do not meet the criteria 
for a probable relationship to the investigational product or administration procedure, 
but for which a connection has reasonable certainty. The following characteristics 
apply: 
− The event occurs after exposure to the investigational product or administration 
procedure, and  


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− The event is not a known reaction to the investigational product or administration 
procedure, but cannot be explained by a commonly occurring alternative etiology, 
or 
− In the absence of a temporal relationship, the event cannot reasonably be explained 
by an alternative etiology.  
• Unlikely: adverse events that, after careful medical evaluation, do not meet the criteria 
for possible or probable relationship to investigational product or administration 
procedure and for which a connection is unlikely. The following characteristics will 
apply: 
− The event does not follow a reasonable temporal sequence from administration of 
the investigational product or administration procedure, or  
− May be explained by commonly occurring alternative etiology in the 
population/individual, or  
− May have been produced by environmental factors, and there is no apparent pattern 
of response to the investigational product or administration procedure.  
An adverse event will be reported as “related” when causality is evaluated by an Investigator as 
probably or possibly related to the investigational product and/or the administration procedure. 
Related adverse events indicate a potential cause-and-effect relationship between the 
investigational product and/or administration procedure and the occurrence of the adverse event.  
An adverse event will be reported as “unrelated” when causality is evaluated by an Investigator as 
unlikely related to the investigational product and/or administration procedure by the Investigator. 
Unrelated adverse events indicate no relationship between the occurrence of the adverse event and 
the investigational product and/or administration procedure.  
13.2.3. 
Recording Adverse Events 
Investigators will monitor all subjects for AEs during the trial and establish a diagnosis for an 
event based on signs, symptoms, and/or other clinical information. It is important to distinguish 
that individual signs and symptoms of the event are not adverse events and should not be reported.  
For each AE, the Investigator will evaluate the causality and severity, report the action taken and 
event outcome and disclose whether or not it caused the subject to discontinue trial participation. 
The following severity scale will be used as a guideline to differentiate the severity of adverse 
events:  
• Mild (Grade 1): Transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required 
• Moderate (Grade 2): Mild to moderate limitation in activity – some assistance may 
be needed; no or minimal medical intervention/therapy required 
• Severe (Grade 3): Marked limitation in activity, some assistance usually required; 
medical intervention/therapy required and often requiring hospitalization or 
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• Life-Threatening or Disabling (Grade 4): Extreme limitation in activity, significant 
assistance required; significant medical intervention/therapy required; hospitalization, 
prolongation of hospitalization, or hospice care 
• Fatal (Grade 5) 
An AE that is assessed as severe should not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event. An event is described as “serious” when it meets one 
of the pre-defined outcomes noted in Section 13.2.1.2. Both an AE and SAE can be assessed as 
severe. However, an AE of severe intensity may not meet SAE definition requirements.  
13.2.4. 
Reporting Adverse Events 
All adverse events are collected from the time of signing informed consent for trial participation 
until completion of 12 months or early termination, whichever occurs first. All AEs occurring after 
the initiation of the IV catheter placement for the initial dose of IP will be considered treatment 
emergent. Any ongoing adverse event that has not been resolved at the time of trial completion or 
early termination for a subject will be marked as ongoing on the adverse event case report form 
(CRF).  
All AEs will be entered into the electronic data capture (EDC) system by trained site personnel at 
the investigative site.   
Expected and unexpected SAEs must be reported to Capricor and entered into the EDC system 
within 24 hours of discovery of the event. For events that do not have complete information 
available at the time of initial report, the investigative site will submit all available information at 
the time of the submission. All SAE Report Forms must be signed by an Investigator and submitted 
with available source documentation. All source documentation must be de-identified prior to 
submission.  
Should access to the EDC system be unavailable, SAEs and subsequent follow-up information 
must be reported to Capricor, or designee, via: 
• Email: 
 
• Fax: 
 
All SAEs must be reported to the respective IRB in accordance with the investigative site’s 
policies. Copies of the submission will be collected by Capricor.   
All SAEs will be reported to the DSMB at least semi-annually, or more frequently at the discretion 
of the Medical Monitor.  
Capricor will promptly upon discovery, report serious and unexpected adverse events for which 
there is a reasonable possibility that the investigative therapy (i.e. administration product and/or 
investigative product) caused the events, to the Food and Drug Administration (FDA) in 
accordance with 21 CFR 312.32 regulations and ICH E2A guidelines.  
For trials conducted under an investigational new drug (IND) application, FDA regulations require 
reporting of any serious suspected adverse reaction that is unexpected according to the current 
Investigator’s Brochure. A serious adverse reaction is defined as any adverse event for which there 
is a reasonable possibility that the drug/biologic caused the AE. For the purposes of IND safety 
reporting, “reasonable possibility” means there is evidence to suggest a causal relationship 


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between the drug/biologic and the adverse event. Serious, unexpected suspected adverse reactions 
(SUSARs) are SAEs that are unexpected and are possibly or probably related to participation in 
the research. Expedited reporting is required for all SUSARs. Capricor will send an IND Safety 
Report to the FDA within 7 calendar days of receipt for fatal/life-threatening events, and within 
15 calendar days of receipt for non-fatal/non-life-threatening events that qualify for expedited 
reporting.  
13.2.5. 
Pregnancy Reporting 
Should a female be impregnated by a trial subject, investigative sites are required to notify Capricor 
within 24 hours of learning about the pregnancy. The investigative site will receive the Pregnancy 
Reporting Form to complete and submit to Capricor, or designee.  
All pregnancies will be followed until the pregnancy outcome is known. In addition, pregnancies 
that are ongoing at the time of trial completion will be followed until the outcome is known. The 
investigative site is responsible for outcome reporting via the Pregnancy Reporting Form, 
including spontaneous or voluntary termination, details of birth, and the presence or absence of 
any birth defects, congenital abnormalities, or maternal and newborn complications.     
The pregnancy is not an adverse event for the male subject unless there is a suspicion that the 
investigational product interfered with the effectiveness of a contraceptive medication. 
13.2.6. 
Adverse Event Follow-up 
All AEs are followed by the investigative site until an outcome is known or the subject’s 
participation in the trial concludes at either 12 months or early termination, whichever occurs first.  
The investigative site is expected to review all ongoing AEs at each visit. AEs are followed until 
resolution or until no further changes in the event are expected (i.e., the point at which a subject 
experiencing an AE is treated successfully and stabilized even though he may continue to 
experience lingering sequelae that may never resolve), or it is agreed that further follow-up of the 
event is not warranted (e.g., non-serious, IP unrelated, ongoing at final visit).  
For SAEs that were incomplete or ongoing at the time of initial submission, the investigative site 
is required to submit follow-up SAE Report Forms when event information is available to the 
research site personnel and/or an outcome is known.  
    


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14. 
STATISTICS 
14.1. 
General Considerations 
The objectives of the trial are to evaluate the safety and efficacy of intravenous infusions of CAP-
1002 administered in four doses at 3-month intervals in subjects with DMD and impairment of 
skeletal muscle function. All statistical tests will be two-sided with 0.05 significance levels. The 
detailed description of the trial statistical methods is provided in the Statistical Analysis Plan 
(SAP). Any deviations from the SAP will be described and justified in the final Clinical Study 
Report. 
14.2. 
Sample Size 
This trial will be limited to a total of 20 randomized subjects.  
14.3. 
Analysis Population 
The following analysis populations will be defined for the trial: 
Safety Population: Subjects who received IP. Safety endpoints for subjects will be summarized 
and analyzed according to the treatment actually received. 
Intent-to-Treat (ITT) Population: Subjects who were randomized. Subjects will be summarized 
and analyzed in the treatment group to which they were randomized. 
Modified Intent-to-Treat (mITT) Population: For each efficacy parameter, the mITT population 
will include subjects in the ITT population who have at least a baseline observation (i.e., mITT 
populations are parameter-specific). Subjects will be summarized and analyzed in the treatment 
group to which they were randomized. 
Per Protocol Population: Subjects who received IP with no protocol deviations/violations that 
could significantly impact the completeness, accuracy and/or reliability of the trial data. The list 
of subjects in the per protocol population will be compiled prior to database lock. 
14.4. 
Safety Analysis 
Safety parameters will be listed, summarized and, if applicable, analyzed for the safety population. 
There are no formal tests of hypotheses associated with the evaluation of safety endpoints.  
14.4.1. 
Safety Endpoints 
The incidence of the following events through the 12-month timepoint will be primary safety 
endpoints: 
• Acute respiratory decompensation within 2 hours following IP administration 
• Hypersensitivity reaction 
• All-cause mortality 
• Serious adverse events 
• Treatment-emergent adverse events related to IP or administration procedure 


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• Immune sensitization syndrome 
The incidence and severity of all AEs will be evaluated as the secondary safety endpoint. 
Treatment groups will be summarized and compared by the incidence of each event type and by 
the subject event rate. Safety during the study will be monitored by the independent, unblinded 
DSMB. See Section 13.2 for more detail on AE data collection and processing. 
14.4.2. 
Adverse Events 
Directly observed and spontaneously reported AEs will be recorded from time of signing informed 
consent (SAEs only) through the end of the trial. AEs will be coded using MedDRA® (Medical 
Dictionary for Regulatory Activities), in which each reported event is mapped to a Preferred Term 
(PT) and a System Organ Class (SOC). A treatment-emergent AE (TEAE) will be defined as an 
AE that was not present prior to the initiation of line placement procedure for the IP infusion or 
was present but worsened in intensity or frequency. All reported AEs will be listed. Both TEAEs 
and non-TEAEs will be summarized, overall and by severity and relationship to the IP and IP 
administration procedure. For each SOC and PT within SOCs, the numbers and percentages of 
subjects reporting an event as well as the number of events that were reported will be calculated. 
Deaths, AEs that resulted in trial discontinuation, SAEs, and AEs within 24 hours of IP 
administration will be listed and summarized separately.  
14.4.3. 
Medications 
Prescription, over-the-counter, and alternative medication use will be coded to drug class, 
preferred drug name, and generic/trade drug name using the World Health Organization drug 
dictionary (WHO-DD). Medications that were stopped before the start of the IP administration 
procedure will be considered “pre-treatment.” All other medications will be considered 
“concomitant.” Medications that were started or ongoing at the time the IP administration 
procedure was started will be considered “baseline” (a subset of “concomitant”). All reported 
medications will be listed. Frequencies and percentages of subjects reporting or receiving each 
medication will be summarized by WHO-DD drug class and preferred name within drug class. 
Pre-treatment and baseline medications will be summarized separately. Separate listings and 
summaries will also be done for cardiac medications and for glucocorticoids.  
14.4.4. 
Clinical Laboratory Evaluations 
Laboratory evaluations will be listed and summarized by visit within each panel (e.g., chemistry, 
hematology, etc.). Summary tables will show means of observed values and changes from baseline 
for observations on a continuous scale and distributions of categorical observations. Shift tables 
may be produced that show frequencies and percentages of subjects that shift from one out-of-
range category at baseline to another out-of-range category at subsequent visits.  
14.4.5. 
Donor-Specific Antibodies 
Donor, donor profile, allele, and MFI will by listed by HLA and visit. Subject HLA profiles will 
be provided in a separate listing.  
DSA data will be analyzed in the context of immune sensitization syndrome should there be an 
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14.4.6. 
Physical Examination 
Observed status (e.g., normal, abnormal) and changes from baseline in body system-specific 
physical examination findings will be summarized by visit within each body system.  
14.4.7. 
12-Lead ECG, Vital Signs, and Weight 
Observed values and changes from baseline will be summarized by visit. 
14.5. 
Efficacy Analysis 
The primary efficacy endpoint will be evaluated in the ITT population, with supportive analyses 
in the mITT and PP populations.  Secondary and exploratory efficacy endpoints will be evaluated 
in the PP population. 
14.5.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is change from baseline to Month 12 in the mid-level (elbow) 
dimension of the PUL 1.2. The hypothesis set to be tested is: 
Ho:  µc - µp = 0 
Ha:  µc - µp ≠ 0 
where µc and µp are population mean absolute changes from baseline in CAP-1002- and placebo-
treated patients, respectively. 
14.5.2. 
Secondary Efficacy Endpoints 
Supportive secondary efficacy endpoints will be change from baseline in: 
•
Mid-level (elbow) PUL1.2 at Months 3, 6, and 9;
•
Regional systolic LV wall thickening at Months 6 and 12
14.5.3. 
Exploratory Efficacy Endpoints 
Exploratory efficacy endpoints will be change from baseline in: 
•
High-level (shoulder) dimension of the PUL 1.2 at Months 3, 6, 9, and 12;
•
High-level (shoulder) dimensions of the PUL 2.0 at Months 3, 6, 9, and 12;
•
Mid-level (elbow) dimensions of the PUL 2.0 at Months 3, 6, 9, and 12;
•
Distal-level (wrist and hand) dimensions of the PUL 1.2 at Months 3, 6, 9, and 12;
•
Distal-level (wrist and hand) dimensions of the PUL 2.0 at Months 3, 6, 9, and 12;
•
Grip strength, absolute and percent predicted, at Months 3, 6, 9, and 12;
•
Tip-to-tip pinch strength, absolute and percent predicted at Months 3, 6, 9, and 12;
•
Key pinch strength, absolute and percent predicted at Months 3, 6, 9, and 12;
•
Elbow flexion strength, absolute and percent predicted, at Months 3, 6, 9, and 12;
•
DMD UL-PROM at Months 3, 6, 9, and 12;


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• PODCI scales (subject and parent) at Months 3, 6, 9, and 12; 
• DMD-LMS at Months 3, 6, 9, and 12; 
• NSAA at Months 3, 6, 9, and 12; 
• 10MWRT at Months 3, 6, 9, and 12; 
• Incidence of loss of ambulation (10MWRT > 30 seconds) at Months 3, 6, 9, and 12; 
• Pulmonary function tests (absolute and percent predicted [if available]) at Months 3, 6, 
9, and 12; 
• LV structure and function as assessed by cardiac MRI at Months 6 and 12; 
• Biomarkers, which may include osteopontin, IL-1ß, IL-2, IL-6, IL-10, TNF-α, 
CXCL10, troponin I (cardiac, fast skeletal, slow skeletal), troponin T, CK-MM, CK-
MB, creatine kinase (total), creatine phosphate, creatinine, myostatin, and follistatin at 
Months 3, 6, 9, and 12; 
• Resource utilization, including hospitalizations for orthopedic injury or surgery and for 
pulmonary infections, over the course of the trial. 
14.6. 
Statistical Methods 
Comparisons between treatment groups on efficacy endpoints will be done using repeated 
measures linear models. Other analyses may also be done using appropriate parametric or non-
parametric methods, depending on distributions of the data and whether or not model assumptions 
are met. An algorithm detailing the decision-making process for performing the primary efficacy 
analysis, in light of features of the data that cannot be known until the data are observed (e.g., 
outliers), will be detailed in the SAP. 
14.6.1. 
Multiplicity 
Trial-wise type 1 error is controlled at the 0.05 level by declaring a primary efficacy endpoint. All 
other efficacy parameters are either supportive secondary or exploratory endpoints and there will 
be no adjustment for multiple analyses. 
14.6.2. 
Missing Data 
Subject-level listings will present data as reported. Missing or partially missing dates that are 
required for date-dependent definitions (eg, treatment-emergent AEs, concomitant medications) 
will be assumed to be the most conservative date possible. For example, an AE with a completely 
missing start date will be considered treatment-emergent; similarly, an AE that started the same 
month and year as IP administration but with missing start day will be considered treatment-
emergent.  
Multiple imputation methods will be used for missing observations for the primary efficacy 
endpoint, if required to prevent subjects from being excluded entirely from analysis. 


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14.6.3. 
Interim Analysis for Futility 
The pre-specified interim analysis was performed. Following the interim analysis, further 
enrollment in the trial was terminated. No further interim analyses are planned.  
 


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15.
TRIAL OVERSIGHT
15.1. 
Steering Committee
The Steering Committee will provide the overall scientific direction for the trial. The 
responsibilities of the Steering Committee are to: (a) maintain contact with trial Investigators to 
ensure high quality data collection; (b) approve and implement major protocol changes; (c) 
collaborate in data analysis, interpretations, and publications; (d) establish criteria for authorship 
on all manuscripts, publications and presentations that arise from the trial.  
15.2. 
Clinical Events Committee (CEC) 
The purpose of CEC adjudication is to provide consistent and unbiased adjudication of clinical 
outcomes and specified events through the independent review of source documentation. The 
charge of the CEC is to review source documents and to adjudicate the classifications of all 
potential primary safety endpoint events. Sites will be provided instructions in the MOP on how 
to collect and submit event information required for CEC review. The CEC will remain blinded to 
subject treatment assignments.  The individuals that serve on the committee will be appointed by 
Capricor, are independent from all other trial activities, and are not affiliated with any investigative 
site. The committee will consist of, at a minimum, a neurologist and pulmonologist with 
experience in treating patients with DMD. Additional experts in immunology will be consultants 
to the committee as necessary. The frequency of CEC meetings is detailed in the CEC Charter.  
15.3. 
Data Safety Monitoring Board 
To meet the trial's ethical responsibility to its subjects, an independent Data Safety Monitoring 
Board will monitor results during the trial.  The board consists of physicians and biostatistician(s) 
appointed by Capricor, who have no formal involvement or conflict of interest with the 
Investigators, investigative sites, subjects, or Capricor. The DSMB will act in a senior advisory 
capacity to Capricor regarding data and safety matters throughout the duration of the trial. The 
board will meet on a periodic basis according to the DSMB charter to monitor the available 
information regarding safety, efficacy, and quality of trial conduct. The DSMB will communicate 
their recommendations directly to Capricor. The investigative sites will have no contact with the 
members of DSMB and no voting member of the committee may participate in the trial as an 
Investigator. 


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16. 
SOURCE DATA AND TRIAL DOCUMENTS 
16.1. 
Electronic Data Capture 
All trial data will be entered into the EDC system. Site personnel requiring access will have their 
own Login/Password. Access to trial information will be based on individual roles and 
responsibilities. The application employs fine-grained role-based access control for data entry, 
viewing and reporting options. All trial data will be transmitted over an encrypted SSL (Secure 
Sockets Layer) connection that requires user authentication.  
This application is designed to be in full compliance with the International Conference on 
Harmonization and Good Clinical Practices (ICH-GCP), the FDA’s CFR 21 Part 11 Electronic 
Record and Electronic Signatures, the FDA’s “Guidance: Computerized Systems Used in Clinical 
Studies,” and Health Insurance Portability and Accountability Act (HIPAA).  
EDC supports efficient data collection and management and facilitates rapid data closure. A strong 
advantage of web-based design is that Capricor, or designee, has immediate access to the data from 
all investigative sites so that queries can be generated and distributed to the sites in real-time and 
the frequency of missing data can be reduced.     
16.2. 
Trial Monitoring 
In accordance with 21 CFR 312.56, ICH- GCP, and local regulations, trial monitors will 
periodically complete on-site monitoring of data with a focus on safety, trial endpoints, data 
completion, data outliers and data integrity. Trial monitors will schedule an on-site visit with a site 
coordinator for an appropriate duration based on the scope of data anticipated to be collected. Prior 
to the visit, a confirmation letter will be sent to the investigative site, which will include a listing 
of which CRFs and source documents will be reviewed.  
Site coordinators are to have all source documents up to date and easily accessible to a monitor.      
During an on-site monitoring visit, trial monitors are to:  
• Track the overall monitoring process including data collected and entered, visit 
schedules, and subject screening and enrollment. 
• Verify and ensure compliance with the protocol according to GCP and HIPAA 
requirements. 
• Ensure that appropriate data corrections are made, dated, explained, and initialed by 
the Investigator or representative. 
• Assess the impact of any personnel changes on the investigative site’s ability to conduct 
the trial.  
• Verify a minimum of the following data points for all subjects: date of birth, signed 
informed consent, eligibility criteria, medical history, date of enrollment, serious AEs, 
and mortalities.  
• Perform review of informed consent process and review documentation of informed 
consent for completeness and correctness.  


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• Perform on-site validation checks of recoded data by reviewing source documents to 
determine whether the data reported in the EDC system are complete and accurate. 
Source documents include medical charts, screening records and/or logs, research 
procedure records and/or files, and other trial related notes.  
• Monitor subject safety by verifying that any AE, therapy modification, or concomitant 
medications are reported in accordance with the protocol.  
• Determine whether all AEs, protocol deviations, and protocol violations are 
appropriately reported within the required time periods according to applicable 
regulatory requirements as outlined in the protocol and by regulatory agencies.  
• Verify that any missed visits, tests, and examinations that were not performed, as well 
as trial withdrawals and/or dropouts are explained and clearly reported. 
• Inform the site PI about any deviations from or violations of the trial protocol, GCP 
and/or regulatory requirements in order for appropriate actions to be taken to prevent 
recurrence of the deviation and/or violation.  
• Infor the Investigator of any major data entry error, delays in data entry, omissions, or 
eligibility requirement errors.  
• Verify that regulatory documentation is accurate, complete, current, and properly 
maintained.  
• Very that PI oversight of trial conduct is documented via signature or initials and date 
on documentation regarding eligibility, AEs, and abnormal laboratory values.  
The monitor may also inspect the investigative site’s facilities to verify that proper space for study 
documents, equipment and investigational product is available.  
A debriefing meeting with the PI, site coordinator(s), and the Monitor to review any notable 
findings will be scheduled toward the end of the on-site visit. The monitor will submit a written 
monitoring visit report to Capricor and send a follow-up letter with findings to the PI. The report 
and letter will include a summary of documentation reviewed by the monitor, any significant 
findings, AEs, protocol deviations and violations, missing regulatory documents and actions taken, 
to be taken or recommended to ensure compliance. The report and letter will include a list of action 
items. Investigative sites are expected to complete the list of actions items within 30 days of 
receipt.  
16.2.1. 
Source Document Requirements 
It is highly recommended that the investigative site uses the CRFs and schedule of assessments 
(Table 3) to develop a plan for identifying and standardizing where source documentation for data 
verification will be collected across all trial participants at their site. As part of trial start-up and 
prior to first enrollment, investigative sites are encouraged to conduct a gap analysis to identify 
any data points that are not routinely documented in the medical record.  
The medical record is the gold standard for source documentation. However, Capricor understands 
that there may be data points required for this trial that are not collected as routine practice at the 
investigative site in the medical record for this patient population. Investigative sites may use the 
provided source document worksheets or create source documents for the purposes of collecting 


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source data that are not included in the medical record. It is important to remember that “source” 
documentation is where the information is first recorded.  
The investigative site must ensure that all subject source documentation is complete, orderly, and 
stored in a secure location. For electronic records, the investigative site should abide by the 
institutional policies for the storage of private health information (PHI). For any paper records 
containing any PHI, the investigative sites must ensure that the files are double-locked, that is, in 
a locked filing cabinet within a locked office or suite.  
All source documentation is to be de-identified of all unique patient and hospital identifiers by the 
investigative site prior to review or submission to Capricor or their designee. 
16.3. 
Audits and Inspections 
Authorized representatives of Capricor, a regulatory authority, an Independent Ethics Committee 
or an Institutional Review Board may visit the site to perform audits or inspections, including 
source data verification.  The purpose of a Capricor audit or inspection is to systematically and 
independently examine all trial-related activities and documents to determine whether these 
activities were conducted, and data were recorded, analyzed, and accurately reported according to 
the protocol, Good Clinical Practice guidelines of the International Conference on Harmonization, 
and any applicable regulatory requirements.  The Investigator should contact Capricor 
immediately if contacted by a regulatory agency about an inspection. 
16.4. 
Retention of Records 
The investigative sites must maintain all documentation relating to the trial for a period of two 
years after the last marketing application approval, or if not approved, two years following the 
discontinuance of the test article for investigation.  If it becomes necessary for Capricor or the 
Regulatory Authority to review any documentation relating to the trial, the Investigator must 
permit access to such records. 


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17. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Capricor will implement and maintain quality control and quality assurance procedures to ensure 
compliance with the protocol, Good Clinical Practices, and all applicable regulatory requirements, 
and may conduct a quality assurance audit(s).  Please see Section 16.3 for more details regarding 
the audit process. 
17.1. 
Qualifications and Trainings 
A representative of Capricor, or designee, will visit the investigative site to determine adequacy of 
the facilities and discuss the feasibility of conducting the trial. 
Clinical Investigators will be physicians with expertise in the clinical care of patients with DMD 
in a multi-disciplinary clinical setting that includes neuromuscular medicine, pulmonary, 
cardiology, and physical therapy.   
Each investigative site MRI lab involved in image acquisition for this trial will be certified by the 
MRI core lab in accordance with the MRI Imaging Manual.  
Each investigative site pulmonary function testing lab involved in conducting pulmonary function 
testing for this trial will be certified by the Pulmonary Function Core Lab as detailed in the Manual 
of Procedures.   
Investigative site personnel delegated to perform the ECG assessment will be certified to perform 
and transmit the assessment by a centralized vendor.   
All Investigators and coordinators will be trained by Capricor, or designee, in the specifics of the 
protocol, investigational product and administration procedure at the site initiation visit in advance 
of the first subject enrollment. The Investigators and coordinators will also undergo a separate 
training to gain familiarity with the electronic data capture system.   
17.2. 
Good Clinical Practices (GCP)  
All Investigators, coordinators and other site personnel involved in care of trial subjects, and/or 
research data collection must provide certification that they have successfully completed their 
institutionally required GCP or other Human Subject Protection courses. Please refer to Section 
6.2 of the Manual of Procedures for specific details regarding certification requirements.  
17.3. 
HIPAA or Other Privacy Training 
All Investigators and coordinators must provide documentation that they have successfully 
completed the institutional requirements to ensure subject rights, privacy and security under 
HIPAA.  
17.4. 
Site Initiation 
IRB approval and the clinical trial agreement between the investigative site and Capricor must be 
signed and executed prior to the site initiation. Additionally, the completed Form FDA 1572, 
applicable CVs and other regulatory documents must be on file with Capricor prior to site 
initiation. A representative from Capricor, or designee, will conduct a site initiation prior to 
enrollment of the first subject. Investigators, study coordinator(s), investigational pharmacist(s), 


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infusion suite personnel, clinical evaluator(s), MRI technologist(s), and laboratory personnel will 
be required to attend the initiation. All other site personnel who may be involved in the trial will 
be encouraged to attend.  
17.5. 
Protocol Deviations 
Efforts to maximize adherence to the protocol will be made through careful and comprehensive 
training, review of trial data collected via the EDC, and routine communication with all site 
Investigators.    
All protocol deviations and violations are to be documented and captured in the EDC. The 
investigative site is responsible for reporting deviations and violations to the IRB per the IRB’s 
reporting guidelines. Capricor will ensure reporting to the proper local and federal regulatory 
authorities in accordance with all applicable federal and local regulations.  
Capricor will determine the course of action based on the severity of the deviation or violation. 
These may include but are not limited to, withdrawal of the subject, additional training at the site, 
additional site monitoring, and/or other appropriate courses of action.  In addition, the Medical 
Monitor and biostatistician will review the circumstances of each deviation and violation (in a 
blinded fashion) to determine whether data can reasonably be included in any trial analyses. 


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18. 
ETHICS 
18.1. 
Ethics Review 
Investigative sites are required to follow their institutional guidelines for obtaining initial approval 
by the IRB and for submitting continuing reviews to the IRB. Subject enrollment at an investigative 
site will not commence until initial IRB approval documentation has been received and reviewed 
by Capricor. The composition and conduct of this committee must conform to the United States 
CFR and ICH E6.  
The informed consent must be reapproved in accordance with the investigative site’s IRB policies 
or at least annually.  
Capricor will provide the investigative sites with DSMB approval letters, serious adverse drug 
reactions and any other applicable correspondences during the trial. Investigative sites are to 
follow their institutional policies for reporting these correspondences and documents to their IRB.  
All IRB approvals and all materials approved/acknowledged by the IRB for this trial, including 
the subject consent/assent form, recruitment materials, or safety event notifications, must be 
maintained by the Investigator and made available for inspection. 
18.2. 
Ethical Conduct of the Trial 
The trial will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/Good Clinical Practice, and applicable 
regulatory requirements. Please reference Section 17 further information.  
In accordance with FDA regulatory requirements, 21 CFR 54.4, the Investigators at each site will 
be required to complete a financial disclosure form provided by Capricor prior to participation in 
the trial. Each Investigator shall provide Capricor sufficient accurate financial information to allow 
Capricor to submit complete and accurate certification or disclosure statements (Forms 3454 
and/or 3455) as required by the FDA regulations. Investigators shall promptly update this 
information if any relevant changes occur in the course of the trial or for 1 year following 
completion of the trial 
18.3. 
Written Informed Consent and Assent 
The Investigator is responsible for ensuring that the informed consent process is conducted and 
documented appropriately by trained site personnel. A signed informed consent, which has been 
approved by Capricor and the individual site IRB, is required for trial participation. The consent 
form must incorporate a clinical research authorization for use and disclosure of private health 
information and a release of medical information that authorizes release of medical records to the 
trial Investigators, monitors, and Capricor. The Investigator, or designated and qualified 
individual, will provide a thorough explanation of objectives, subject responsibilities, risks and 
benefits of the trial, and will fully address all concerns raised by the subject and/or legal guardian. 
After all issues have been adequately resolved, and the Investigator confirms that the subject has 
been fully consented, the subject or his legal guardian will be asked to sign the informed consent. 
The consent process must be documented in the medical chart and a signed copy of the consent 
and/or assent must be given to the subject and/or legal guardian.  


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18.3.1. 
Obtaining Informed Consent and Assent 
The Investigators at each center will ensure that the subject and legal guardian (applicable only if 
the subject is < 18 years of age) are given full and adequate oral and written information about the 
nature, purpose, possible risk and benefit of the trial.  The subject and legal guardian must also be 
notified that they are free to discontinue from the trial at any time.  The subject and legal guardian 
should be given the opportunity to ask questions and allowed time to consider the information 
provided. 
The subject must sign and date the informed consent form prior to performing any trial procedures. 
If the subject is < 18 years of age, the subject must sign and date the assent form and a legal 
guardian must sign and date the informed consent form prior to performing any trial procedures. 
Specific requirements and guidelines for providing assent will be determined by the investigative 
site’s IRB.   
18.4. 
Subject Confidentiality 
Confidentiality of all subject records will be maintained according to HIPAA guidelines. 
Investigators, investigative site IRBs, Capricor, CEC, and the FDA may review source 
documentation for enrolled subjects as necessary, but all unique patient and hospital identifiers 
will be removed prior to review. If the results of this trial are published, the data will be presented 
in aggregate, with all subject identifiers removed.  
 
 
 
 
 


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19. 
PUBLICATION POLICY 
Recognizing the importance of communicating clinical trial results to the public and the medical 
and scientific communities in an accurate and complete manner, the first publication of the trial, 
to include results from all of the investigative centers in a multi-center publication, will be authored 
by the lead or national Principal Investigator, and/or other designees assigned by the Steering 
Committee, for publication in a peer-reviewed scientific journal. All participating Investigators, 
key site personnel, committees and committee members will be listed in an appendix as part of the 
main manuscript.  
An individual Investigator has the right to publish his/her data after the multi-center publication, 
unless no such multi-center publication is so published before the first anniversary of the 
finalization of the multi-center database, in which case the Investigator may publish or submit for 
publication a manuscript without further delay according to the terms and conditions in the Clinical 
Trial Agreement. 
Additional manuscripts targeting exploratory endpoints or other endpoints or data not included in 
the first multi-center publication are anticipated and encouraged. In such cases, the Investigator(s) 
should submit ideas for these additional manuscripts to the Steering Committee that will serve as 
the clearing house to approve topics, ensure that activity between the Investigator(s) in analyzing 
the data is coordinated, prioritize data analyses and help determine authorship. 
 


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20. 
REFERENCES 
1. Aartsma-Rus A., J.C. Van Deutekom, I.F. Fokkema, G.J. Van Ommen, J.T. Den Dunnen 
(2006). "Entries in the Leiden Duchenne muscular dystrophy mutation database: an 
overview of mutation types and paradoxical cases that confirm the reading-frame rule." 
Muscle Nerve 34(2):135-44.  
2. Aartsma-Rus, A. (2014). "Dystrophin Analysis in Clinical Trials." J Neuromuscul Dis 
1(1):41-53. 
3. Aartsma-Rus, A., I. B. Ginjaar and K. Bushby (2016). "The importance of genetic 
diagnosis for Duchenne muscular dystrophy." J Med Genet 53(3): 145-151. 
4. Aminzadeh, M. A., R. G. Rogers, K. Gouin, M. Fournier, R. E. Tobin, X. Guan, M. K. 
Childers, A. M. Andres, D. J. Taylor, A. G. Ibrahim, X. Ding, A. Torrente, J. I. Goldhaber, 
R. A. Victor, R. A. Gottlieb, M. Lewis and E. Marban (2017). Reversal of cardiac and 
skeletal manifestations of Duchenne muscular dystrophy by cardiosphere-derived cells and 
their exosomes in mdx dystrophic mice and in human Duchenne cardiomyocytes. 
http://biorxiv.org/content/early/2017/04/20/128900 
5. Bonios, M., J. Terrovitis, C. Y. Chang, J. M. Engles, T. Higuchi, R. Lautamaki, J. Yu, J. 
Fox, M. Pomper, R. L. Wahl, B. M. Tsui, B. O'Rourke, F. M. Bengel, E. Marban and M. 
R. Abraham (2011). "Myocardial substrate and route of administration determine acute 
cardiac retention and lung bio-distribution of cardiosphere-derived cells." J Nucl Cardiol 
18(3): 443-450. 
6. Bulfield, G., W. G. Siller, P. A. Wight and K. J. Moore (1984). "X chromosome-linked 
muscular dystrophy (mdx) in the mouse." Proc Natl Acad Sci U S A 81(4): 1189-1192. 
7. Bushby, K., R. Finkel, D. J. Birnkrant, L. E. Case, P. R. Clemens, L. Cripe, A. Kaul, K. 
Kinnett, C. McDonald, S. Pandya, J. Poysky, F. Shapiro, J. Tomezsko, C. Constantin and 
D. M. D. C. C. W. Group (2010). "Diagnosis and management of Duchenne muscular 
dystrophy, part 1: diagnosis, and pharmacological and psychosocial management." Lancet 
Neurol 9(1): 77-93. 
8. Bushby, K., R. Finkel, D. J. Birnkrant, L. E. Case, P. R. Clemens, L. Cripe, A. Kaul, K. 
Kinnett, C. McDonald, S. Pandya, J. Poysky, F. Shapiro, J. Tomezsko, C. Constantin and 
D. M. D. C. C. W. Group (2010). "Diagnosis and management of Duchenne muscular 
dystrophy, part 2: implementation of multidisciplinary care." Lancet Neurol 9(2): 177-189. 
9. Chambers, D. C., D. Enever, S. Lawrence, M. J. Sturm, R. Herrmann, S. Yerkovich, M. 
Musk and P. M. Hopkins (2017). "Mesenchymal Stromal Cell Therapy for Chronic Lung 
Allograft Dysfunction: Results of a First-in-Man Study." Stem Cells Transl Med 6(4): 
1152-1157. 
10. Deconinck, N. and B. Dan (2007). "Pathophysiology of duchenne muscular dystrophy: 
current hypotheses." Pediatr Neurol 36(1): 1-7. 
11. den Dunnen J.T. (2014). "Leiden DMD Mutation Database" www.dmd.nl 


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12. Dumont, N. A., Y. X. Wang, J. von Maltzahn, A. Pasut, C. F. Bentzinger, C. E. Brun and 
M. A. Rudnicki (2015). "Dystrophin expression in muscle stem cells regulates their 
polarity and asymmetric division." Nat Med 21(12): 1455-1463. 
13. Emery, A. E. (2002). "The muscular dystrophies." Lancet 359(9307): 687-695. 
14. Evans, J.A., W.A. Whitelaw (2009). "The assessment of maximal respiratory mouth 
pressures in adults." Respir Care 54(10):1348-59. 
15. Fairclough, R. J., M. J. Wood and K. E. Davies (2013). "Therapy for Duchenne muscular 
dystrophy: renewed optimism from genetic approaches." Nat Rev Genet 14(6): 373-378. 
16. Falzarano, M. S., C. Scotton, C. Passarelli and A. Ferlini (2015). "Duchenne Muscular 
Dystrophy: From Diagnosis to Therapy." Molecules 20(10): 18168-18184. 
17. Gauld, L. M., J. Kappers, J.B. Carlin, C.F. Robertson (2004). "Height prediction from ulna 
length." Dev Med Child Neurol 46(7):475-80. 
18. Hendriksen, R. G., G. Hoogland, S. Schipper, J. G. Hendriksen, J. S. Vles and M. W. 
Aalbers (2015). "A possible role of dystrophin in neuronal excitability: a review of the 
current literature." Neurosci Biobehav Rev 51: 255-262. 
19. Henricson, E. K., R. T. Abresch, A. Cnaan, F. Hu, T. Duong, A. Arrieta, J. Han, D. M. 
Escolar, J. M. Florence, P. R. Clemens, E. P. Hoffman, C. M. McDonald and C. 
Investigators (2013). "The cooperative international neuromuscular research group 
Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful 
functional milestones and reduces rate of disease progression as measured by manual 
muscle testing and other commonly used clinical trial outcome measures." Muscle Nerve 
48(1): 55-67. 
20. Hoffman, E. P., R. H. Brown and L. M. Krunkel (1987). "Dystrophin: the protein product 
of the Duchenne muscular dystrophy locus." Cell 51(6): 919-928. 
21. Hong, S. J., D. Hou, T. J. Brinton, B. Johnstone, D. Feng, P. Rogers, W. F. Fearon, P. Yock 
and K. L. March (2014). "Intracoronary and retrograde coronary venous myocardial 
delivery of adipose-derived stem cells in swine infarction lead to transient myocardial 
trapping with predominant pulmonary redistribution." Catheter Cardiovasc Interv 83(1): 
E17-25. 
22. Hor, K.N., M.D. Taylor, H.R. Al-Khalidi, L.H. Cripe, S.V. Raman, J.L. Jefferies, R. 
O'Donnell, D.W. Benson, W. Mazur (2013). “Prevalence and distribution of late 
gadolinium enhancement in a large population of patients with Duchenne muscular 
dystrophy: effect of age and left ventricular systolic function.” J Cardiovasc Magn Reson 
15(1): 107.  
23. Ibrahim, A. G., K. Cheng and E. Marban (2014). "Exosomes as critical agents of cardiac 
regeneration triggered by cell therapy." Stem Cell Reports 2(5): 606-619. 
24. Kanazawa, H., E. Tseliou, K. Malliaras, K. Yee, J. F. Dawkins, G. De Couto, R. R. Smith, 
M. Kreke, J. Seinfeld, R. C. Middleton, R. Gallet, K. Cheng, D. Luthringer, I. Valle, S. 
Chowdhury, K. Fukuda, R. R. Makkar, L. Marban and E. Marban (2015). "Cellular 
postconditioning: allogeneic cardiosphere-derived cells reduce infarct size and attenuate 


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microvascular obstruction when administered after reperfusion in pigs with acute 
myocardial infarction." Circ Heart Fail 8(2): 322-332. 
25. Koenig, M., A. P. Monaco and L. M. Kunkel (1988). "The complete sequence of dystrophin 
predicts a rod-shaped cytoskeletal protein." Cell 53(2): 219-228. 
26. Mah J.K., L. Korngut, J. Dykeman, L. Day, T. Pringsheim, N. Jette. (2014). "A systematic 
review and meta-analysis on the epidemiology of Duchenne and Becker muscular 
dystrophy." Neuromuscul Disord 24(6):482-91. 
27. Malliaras, K., R. R. Smith, H. Kanazawa, K. Yee, J. Seinfeld, E. Tseliou, J. F. Dawkins, 
M. Kreke, K. Cheng, D. Luthringer, C. S. Ho, A. Blusztajn, I. Valle, S. Chowdhury, R. R. 
Makkar, R. Dharmakumar, D. Li, L. Marban and E. Marban (2013). "Validation of 
contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell 
therapy in a porcine model of convalescent myocardial infarction." Circulation 128(25): 
2764-2775. 
28. Malliaras, K., T. S. Li, D. Luthringer, J. Terrovitis, K. Cheng, T. Chakravarty, G. Galang, 
Y. Zhang, F. Schoenhoff, J. Van Eyk, L. Marban and E. Marban (2012). "Safety and 
efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched 
cardiosphere-derived cells." Circulation 125(1): 100-112. 
29. Mercuri, E., J.E. Signorovitch, E. Swallow, J. Song, S.J. Ward (2016). “Categorizing 
natural history trajectories of ambulatory function measured by the 6-minute walk distance 
in patients with Duchenne muscular dystrophy.” Neuromuscul Disord 26(9):576-83.  
30. Muntoni, F., S. Torelli and A. Ferlini (2003). "Dystrophin and mutations: one gene, several 
proteins, multiple phenotypes." Lancet Neurol 2(12): 731-740. 
31. Pane M., E.S. Mazzone, L. Fanelli, R. De Sanctis, F. Bianco, S. Sivo, A. D'Amico, S. 
Messina, R. Battini, M. Scutifero, R. Petillo, S. Frosini, R. Scalise, G. Vita, C. Bruno, M. 
Pedemonte, T. Mongini, E. Pegoraro, F. Brustia, A. Gardani, A. Berardinelli, V. 
Lanzillotta, E. Viggiano, F. Cavallaro, M. Sframeli, L. Bello, A. Barp, S. Bonfiglio, E. 
Rolle, G. Colia, M. Catteruccia, C. Palermo, G. D'Angelo, A. Pini, E. Iotti, K. Gorni, G. 
Baranello, L. Morandi, E. Bertini, L. Politano, M. Sormani, E. Mercuri (2014). "Reliability 
of the Performance of Upper Limb assessment in Duchenne muscular dystrophy." 
Neuromuscul Disord 24(3):201-6.  
32. Puchalski, M.D., R.V. Williams, B. Askovich, C.T. Sower, K.H. Hor, J.T. Su, N. Pack, E. 
Dibella, W.M. Gottliebson (2009). “Late gadolinium enhancement: precursor to 
cardiomyopathy in Duchenne muscular dystrophy?”  Int J Cardiovasc Imaging 25(1):57-
63. 
33. Reich, H., E. Tseliou, G. de Couto, D. Angert, J. Valle, Y. Kubota, D. Luthringer, J. 
Mirocha, B. Sun, R. R. Smith, L. Marban and E. Marban (2016). "Repeated transplantation 
of allogeneic cardiosphere-derived cells boosts therapeutic benefits without immune 
sensitization in a rat model of myocardial infarction." J Heart Lung Transplant 35(11): 
1348-1357. 
34. Weiss, D. J., R. Casaburi, R. Flannery, M. LeRoux-Williams and D. P. Tashkin (2013). "A 
placebo-controlled, randomized trial of mesenchymal stem cells in COPD." Chest 143(6): 
1590-1598. 


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35. White S.J., J.T. den Dunnen (2006). "Copy number variation in the genome; the human 
DMD gene as an example." Cytogenet Genome Res 115(3-4):240-6. 
36. Wilson, J. G., K. D. Liu, H. Zhuo, L. Caballero, M. McMillan, X. Fang, K. Cosgrove, R. 
Vojnik, C. S. Calfee, J. W. Lee, A. J. Rogers, J. Levitt, J. Wiener-Kronish, E. K. Bajwa, A. 
Leavitt, D. McKenna, B. T. Thompson and M. A. Matthay (2015). "Mesenchymal stem 
(stromal) cells for treatment of ARDS: a phase 1 clinical trial." Lancet Respir Med 3(1): 
24-32. 


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21. 
APPENDICES 
21.1. 
Appendix I: Exon 44-Skip Amenable Dystrophin Mutations 
Deletions to the following exons of the dystrophin gene are amenable to exon-44 skipping (den 
Dunnen J.T., 2014; White and den Dunnen, 2006; Aartsma-Rus et al., 2006; Aartsma-Rus, 2014): 
10-43 
24-43 
34-43 
45 
11-43 
25-43 
35-43 
45-54 
13-43 
26-43 
36-43 
45-56 
14-43 
27-43 
37-43 
45-62 
15-43 
28-43 
38-43 
 
16-43 
29-43 
39-43 
 
17-43 
30-43 
40-43 
 
19-43 
31-43 
41-43 
 
21-43 
32-43 
42-43 
 
23-43 
33-43 
43 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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21.2. 
Appendix II: Pre-Infusion Guidance for Minimizing Risk of Potential 
Severe Hypersensitivity Reaction    
As discussed in Section 10.6, Capricor requires treatment of all subjects prior to each IP infusion 
to minimize the risk of a potential severe allergic reaction. It is strongly encouraged that pre-
medication be administered according to the guidelines in Table 6 including the administration of 
high dose steroids, H1 and H2 blockers; however, investigative sites may use institutional 
protocols established for anaphylaxis prevention should they be at least physiologically 
comparable to the guidelines below.   
Final decisions regarding the medication(s), dose(s) administered, and route(s) of administration 
are to be determined by the Investigator taking into consideration the subject’s medical history. 
For any pre-treatment medication administered, the FDA approved label should be reviewed for 
information on potential side effects and/or drug interactions and followed for detailed instructions 
on weight-based dosing. 
Of note, for subjects routinely treated with beta blocker and ACEi, the doses of both should be 
held on the day of infusion, if clinically acceptable in the judgment of the site Investigator. 
Furthermore, it is recommended that the standing steroid doses should be held if the planned 
schedule is within 24 hours of the time of scheduled infusion of IP. This is because glucocorticoids 
will likely be administered as part of the pre-medications beginning 12 – 14 hours prior to infusion 
of IP.